Cyclosporine

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

In vitro cerivastatin metabolism

exposure

Cyclosporin A

limitations

Recorded as the measured null that separates the two candidate mechanisms for this interaction. The authors conclude the interaction is mainly transporter inhibition, which is an interpretation of these two numbers rather than a separate measurement.

organism

In vitro cerivastatin metabolism

plain_language

Cyclosporin A inhibited the in vitro metabolism of labelled cerivastatin only at concentrations above 30 micromolar, two orders of magnitude above the concentrations that inhibited its transport.

primary_references

Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. (2003). https://pubmed.ncbi.nlm.nih.gov/12538813/ DOI: 10.1124/jpet.102.041921

route

In vitro

tissue

Drug metabolism

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 168–168

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · In vitro cerivastatin metabolism · source_derived_draft · unverified_draft

Cyclosporin A inhibited the in vitro metabolism of labelled cerivastatin only at concentrations above 30 micromolar, two orders of magnitude above the concentrations that inhibited its transport.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human and mammalian immunophilin biochemistry

exposure

Cyclosporin A

limitations

The report states that inhibition of isomerase activity is not what produces the drug's effect; analysis of cyclosporin-resistant yeast mutants and other isomerase inhibitors pointed to an inhibitory drug-isomerase complex instead. Binding is recorded here without a direction, because binding a protein is not by itself raising or lowering it.

organism

Human and mammalian immunophilin biochemistry

plain_language

The immediate intracellular receptor of cyclosporin A is cyclophilin, a peptidyl-prolyl cis-trans isomerase, and drug binding inhibits that isomerase activity.

primary_references

Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. (1991). https://pubmed.ncbi.nlm.nih.gov/1715516/ DOI: 10.1038/352803a0

route

In vitro

tissue

T-lymphocyte signalling

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 14–14

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Human and mammalian immunophilin biochemistry · source_derived_draft · unverified_draft

The immediate intracellular receptor of cyclosporin A is cyclophilin, a peptidyl-prolyl cis-trans isomerase, and drug binding inhibits that isomerase activity.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat liver and heart mitochondria

exposure

Cyclosporin A titration

limitations

This is a different cyclophilin from the cytosolic one that carries the immunosuppressive mechanism, and the two must not be merged. The 1990 report identifies a matrix isomerase by activity and binding site number; the gene assignment to Ppif came later and is not part of this measurement.

organism

Rat liver and heart mitochondria

plain_language

Liver and heart mitochondrial matrix fractions, prepared free of membrane and cytosolic contamination, contain cyclosporin-sensitive peptidyl-prolyl cis-trans isomerase, titrated at 110.6 plus or minus 10.1 and 165.4 plus or minus 15.0 picomoles of enzyme per milligram of protein with a Ki of about 2.5 nanomolar.

primary_references

Inhibition of Ca2+-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase. (1990). https://pubmed.ncbi.nlm.nih.gov/2160810/ DOI: 10.1042/bj2680153

route

In vitro

tissue

Mitochondrial matrix peptidyl-prolyl isomerase

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 124–124

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat liver and heart mitochondria · source_derived_draft · unverified_draft

Liver and heart mitochondrial matrix fractions, prepared free of membrane and cytosolic contamination, contain cyclosporin-sensitive peptidyl-prolyl cis-trans isomerase, titrated at 110.6 plus or minus 10.1 and 165.4 plus or minus 15.0 picomoles of enzyme per milligram of protein with a Ki of about 2.5 nanomolar.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

T lymphocytes

exposure

Cyclosporin A; FK506 compared alongside

limitations

Synthesis of the nuclear subunit was not affected, so the block is on translocation rather than on making the factor. The abstract does not give concentrations or a time course.

organism

T lymphocytes

plain_language

NFAT is assembled when an antigen-receptor signal drives a pre-existing cytoplasmic subunit into the nucleus to join a newly synthesised nuclear subunit, and cyclosporin A blocks translocation of the cytoplasmic component.

primary_references

Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. (1991). https://pubmed.ncbi.nlm.nih.gov/1715516/ DOI: 10.1038/352803a0

route

In vitro

tissue

Antigen-receptor signalling to cytokine genes

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 102–102

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · T lymphocytes · source_derived_draft · unverified_draft

NFAT is assembled when an antigen-receptor signal drives a pre-existing cytoplasmic subunit into the nucleus to join a newly synthesised nuclear subunit, and cyclosporin A blocks translocation of the cytoplasmic component.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

A measured null that places the effect at the distal convoluted tubule rather than at the paracellular magnesium route of the thick ascending limb. Expression was the readout; paracellular permeability was not measured.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Cyclosporine did not change renal expression of claudin-16 in the same rat model in which it lowered TRPM6, TRPM7, NCC and EGF.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Kidney

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 278–278

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Cyclosporine did not change renal expression of claudin-16 in the same rat model in which it lowered TRPM6, TRPM7, NCC and EGF.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

The two claudins were reported together as unchanged, so this null and the claudin-16 null are one measurement read twice and are not independent of each other.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Cyclosporine did not change renal expression of claudin-19 in the same rat model, reported alongside the unchanged claudin-16.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Kidney

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 289–289

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Cyclosporine did not change renal expression of claudin-19 in the same rat model, reported alongside the unchanged claudin-16.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Mammalian immunophilin biochemistry, with cyclosporin-resistant yeast mutants cited as support

exposure

Cyclosporin A with cyclophilin

limitations

This is the step that makes the drug an inhibitor of anything, and it is why no arrow in this collection runs from cyclosporine to calcineurin directly. The evidence cited for it in this report is the behaviour of other isomerase inhibitors and of cyclosporin-resistant yeast mutants, which is an argument from the pattern of results rather than a measurement of complex formation.

organism

Mammalian immunophilin biochemistry, with cyclosporin-resistant yeast mutants cited as support

plain_language

The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug binding also causes.

primary_references

Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. (1991). https://pubmed.ncbi.nlm.nih.gov/1715516/ DOI: 10.1038/352803a0

route

In vitro

tissue

Formation of the drug-immunophilin complex

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 25–25

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Mammalian immunophilin biochemistry, with cyclosporin-resistant yeast mutants cited as support · source_derived_draft · unverified_draft

The effects of cyclosporin A are reported to follow from the formation of an inhibitory complex between the drug and its prolyl isomerase, and not from inhibition of the isomerase activity that drug binding also causes.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human OATP2 (OATP1B1 / SLCO1B1) expressed in MDCKII cells

exposure

Cyclosporin A

limitations

The transporter is named OATP2 in this 2003 report, which is the protein now called OATP1B1 and encoded by SLCO1B1; the same entity is reused here rather than forked. The Ki is for cerivastatin as the probe substrate and does not transfer unchanged to other OATP1B1 substrates.

organism

Human OATP2 (OATP1B1 / SLCO1B1) expressed in MDCKII cells

plain_language

Cyclosporin A inhibited OATP2-mediated uptake of labelled cerivastatin in transporter-expressing MDCKII cells with a Ki of 0.2 micromolar.

primary_references

Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. (2003). https://pubmed.ncbi.nlm.nih.gov/12538813/ DOI: 10.1124/jpet.102.041921

route

In vitro

tissue

Hepatic sinusoidal uptake transport

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 146–146

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Human OATP2 (OATP1B1 / SLCO1B1) expressed in MDCKII cells · source_derived_draft · unverified_draft

Cyclosporin A inhibited OATP2-mediated uptake of labelled cerivastatin in transporter-expressing MDCKII cells with a Ki of 0.2 micromolar.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat liver and heart mitochondria

exposure

Cyclosporin A, titrated

limitations

Isolated mitochondria under respiratory-chain inhibition in KSCN or sucrose medium, with 250 micromolar calcium, which is a supraphysiological calcium load in a stripped system. Bongkrekic acid inhibited swelling in both media and ADP inhibited it in KSCN medium with the effect reversed by carboxyatractyloside, so the adenine nucleotide carrier is implicated alongside the isomerase. The proposed interaction between the two is the authors' model, not a measurement.

organism

Rat liver and heart mitochondria

plain_language

Cyclosporin A inhibited the large-amplitude swelling that isolated rat liver and heart mitochondria show when exposed to 250 micromolar calcium, with the number of cyclosporin-binding sites titrated at 113.7 plus or minus 5.0 and 124.3 plus or minus 11.2 picomoles per milligram of protein and a Ki of about 5 nanomolar.

primary_references

Inhibition of Ca2+-induced large-amplitude swelling of liver and heart mitochondria by cyclosporin is probably caused by the inhibitor binding to mitochondrial-matrix peptidyl-prolyl cis-trans isomerase and preventing it interacting with the adenine nucleotide translocase. (1990). https://pubmed.ncbi.nlm.nih.gov/2160810/ DOI: 10.1042/bj2680153

route

In vitro

tissue

Calcium-induced inner-membrane pore opening

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 135–135

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat liver and heart mitochondria · source_derived_draft · unverified_draft

Cyclosporin A inhibited the large-amplitude swelling that isolated rat liver and heart mitochondria show when exposed to 250 micromolar calcium, with the number of cyclosporin-binding sites titrated at 113.7 plus or minus 5.0 and 124.3 plus or minus 11.2 picomoles per milligram of protein and a Ki of about 5 nanomolar.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

A hormone measurement in rats. The link from the lower aldosterone to the lower cotransporter is the authors' interpretation of two associated findings.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Serum aldosterone was significantly lower in cyclosporine-treated rats, and the authors read the fall in the sodium-chloride cotransporter as following an inactivated renin-angiotensin-aldosterone system.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Renin-angiotensin-aldosterone system

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 322–322

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Serum aldosterone was significantly lower in cyclosporine-treated rats, and the authors read the fall in the sodium-chloride cotransporter as following an inactivated renin-angiotensin-aldosterone system.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Human hepatocytes from three donors

exposure

Cyclosporin A

limitations

The pool that falls is the hepatocyte interior. Plasma exposure is expected to move the other way and was not measured here. Three donors is a small panel for a kinetic range.

organism

Human hepatocytes from three donors

plain_language

Uptake of labelled cerivastatin into human hepatocytes from three donors was inhibited by cyclosporin A with Ki values of 0.3 to 0.7 micromolar, against Km values for the uptake itself of 3 to 18 micromolar, so more than 70 per cent of total uptake at therapeutic concentrations was carrier-mediated.

primary_references

Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A. (2003). https://pubmed.ncbi.nlm.nih.gov/12538813/ DOI: 10.1124/jpet.102.041921

route

In vitro

tissue

Hepatocyte interior

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 157–157

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Human hepatocytes from three donors · source_derived_draft · unverified_draft

Uptake of labelled cerivastatin into human hepatocytes from three donors was inhibited by cyclosporin A with Ki values of 0.3 to 0.7 micromolar, against Km values for the uptake itself of 3 to 18 micromolar, so more than 70 per cent of total uptake at therapeutic concentrations was carrier-mediated.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

T lymphocytes

exposure

Cyclosporin A

limitations

The same report records little or no effect on other transcription factors such as AP-1 and NF-kappa B, so this is selectivity for the NFAT route rather than general transcriptional shutdown. AP-1 and NF-kappa B are not recorded as separate entities here because the abstract reports them only as unaffected comparators.

organism

T lymphocytes

plain_language

Transcription directed by NFAT is blocked in T cells treated with cyclosporin A, which is why the drug reaches the cytokine genes that coordinate the immune response.

primary_references

Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. (1991). https://pubmed.ncbi.nlm.nih.gov/1715516/ DOI: 10.1038/352803a0

route

In vitro

tissue

Cytokine gene transcription

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 113–113

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · T lymphocytes · source_derived_draft · unverified_draft

Transcription directed by NFAT is blocked in T cells treated with cyclosporin A, which is why the drug reaches the cytokine genes that coordinate the immune response.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

Rat expression data. Sodium loss is attributed rather than separately quantified in the abstract.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Cyclosporine significantly decreased renal expression of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule, which the authors link to the renal sodium loss.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Distal convoluted tubule

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 311–311

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Cyclosporine significantly decreased renal expression of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule, which the authors link to the renal sodium loss.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

This is the step that makes the magnesium loss a signalling failure rather than direct channel blockade, but the abstract reports the two falls together without demonstrating that one causes the other in this model.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Cyclosporine significantly decreased renal expression of epidermal growth factor in the same rat model.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Kidney

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 245–245

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Cyclosporine significantly decreased renal expression of epidermal growth factor in the same rat model.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity, with the human observation as the stated background

exposure

Cyclosporine, dose and duration not stated here

limitations

The human magnesium loss is cited as established background in this report rather than measured in it. The rat measurement is the transporter expression and the fractional excretion, and the causal attribution between them is the authors' reading.

organism

Rat model of cyclosporine nephrotoxicity, with the human observation as the stated background

plain_language

Renal magnesium loss is a well-known effect of cyclosporine treatment in people, and in this rat model the authors attribute it to downregulation of TRPM6 in the distal convoluted tubule.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Renal magnesium handling

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 300–300

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity, with the human observation as the stated background · source_derived_draft · unverified_draft

Renal magnesium loss is a well-known effect of cyclosporine treatment in people, and in this rat model the authors attribute it to downregulation of TRPM6 in the distal convoluted tubule.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

Rat expression data. The authors read this as the molecular basis of the renal magnesium loss seen in people given cyclosporine, which is a cross-species interpretation and is recorded as one. Expression is not the same as channel activity.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Cyclosporine significantly decreased renal expression of the magnesium channel TRPM6 in a rat model of cyclosporine nephrotoxicity.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Distal convoluted tubule

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 223–223

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Cyclosporine significantly decreased renal expression of the magnesium channel TRPM6 in a rat model of cyclosporine nephrotoxicity.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Rat model of cyclosporine nephrotoxicity

exposure

Cyclosporine, dose and duration not stated here

limitations

Rat expression data, reported together with TRPM6 without separating their contributions to the magnesium loss.

organism

Rat model of cyclosporine nephrotoxicity

plain_language

Cyclosporine significantly decreased renal expression of TRPM7 alongside TRPM6 in the same rat model.

primary_references

Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. (2011). https://pubmed.ncbi.nlm.nih.gov/21653632/ DOI: 10.1152/ajprenal.00116.2011

route

In vivo

tissue

Kidney

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 234–234

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Rat model of cyclosporine nephrotoxicity · source_derived_draft · unverified_draft

Cyclosporine significantly decreased renal expression of TRPM7 alongside TRPM6 in the same rat model.

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

Heterologously expressed human CYP3A4

exposure

Cyclosporin A

limitations

Substrate inhibition means the rate does not rise linearly with concentration, so a single-point rate from this system does not scale. The step consumes the parent drug, which is the direction recorded.

organism

Heterologously expressed human CYP3A4

plain_language

Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.

primary_references

In vitro metabolism of cyclosporine A by human kidney CYP3A5. (2004). https://pubmed.ncbi.nlm.nih.gov/15450954/ DOI: 10.1016/j.bcp.2004.07.012

route

In vitro

tissue

Oxidative drug metabolism

Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 179–179

Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Heterologously expressed human CYP3A4 · source_derived_draft · unverified_draft

Heterologously expressed CYP3A4 produced three primary cyclosporine metabolites, AM1, AM9 and AM4N, with substrate inhibition observed for AM1 and AM9 formation.

dose

Capsaicin with capsazepine or cyclosporine controls

duration

Acute

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Primary cardiomyocytes; rat reperfusion model for downstream peptide work

limitations

The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Primary cardiomyocytes; rat reperfusion model for downstream peptide work

plain_language

Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect.

primary_references

Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774

route

In vitro

tissue

Mitochondrial TRPV1 and membrane potential

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary cardiomyocytes; rat reperfusion model for downstream peptide work · source_derived_draft · unverified_draft

## capsaicin-cardiomyocyte-mitochondria Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect. Model/species: Primary cardiomyocytes; rat reperfusion model for downstream peptide work Tissue/system: Mitochondrial TRPV1 and membrane potential Exposure: Capsaicin with capsazepine or cyclosporine controls Route: In vitro Duration: Acute Limits: The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result. Primary reference: Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

availability_state

machinery_impairment Imported condition classification; unverified.

dose

Hydroxytyrosol with compound C or cyclosporine

duration

Cell assay accompanying fish feeding

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Zebrafish liver cell line with an eight-week spotted-seabass feeding arm

limitations

This fish/cell mechanism is not direct evidence for human liver disease or a clinical drug interaction.

nutrient_topic

Hydroxytyrosol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Hydroxytyrosol

organism

Zebrafish liver cell line with an eight-week spotted-seabass feeding arm

plain_language

Compound C blocked hydroxytyrosol-associated PINK1 mitophagy in zebrafish liver cells, and cyclosporine blocked the measured mitochondrial benefits.

primary_references

Hydroxytyrosol Promotes the Mitochondrial Function through Activating Mitophagy. (2022). https://pubmed.ncbi.nlm.nih.gov/35624756/ DOI: 10.3390/antiox11050893

route

In vitro perturbation

tissue

AMPK/PINK1 mitophagy and mitochondrial function

trigger_kind

machinery_impairment Imported condition classification; unverified.

Hydroxytyrosol: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Zebrafish liver cell line with an eight-week spotted-seabass feeding arm · source_derived_draft · unverified_draft

## hydroxytyrosol-ampk-pink1-mitophagy Compound C blocked hydroxytyrosol-associated PINK1 mitophagy in zebrafish liver cells, and cyclosporine blocked the measured mitochondrial benefits. Model/species: Zebrafish liver cell line with an eight-week spotted-seabass feeding arm Tissue/system: AMPK/PINK1 mitophagy and mitochondrial function Exposure: Hydroxytyrosol with compound C or cyclosporine Route: In vitro perturbation Duration: Cell assay accompanying fish feeding Limits: This fish/cell mechanism is not direct evidence for human liver disease or a clinical drug interaction. Primary reference: Hydroxytyrosol Promotes the Mitochondrial Function through Activating Mitophagy. (2022). https://pubmed.ncbi.nlm.nih.gov/35624756/ DOI: 10.3390/antiox11050893 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.