Kidney drug metabolizing activities in streptozotocin diabetic rats

Villar, Eugenia Del; Gaule, Carlos; Vega, Paula Vega

doi:10.1016/0306-3623(94)00163-h

“…In STZ-induced diabetic rats, formations of hydroxyandrostenedione and 2α-hydroxytestosterone were significantly increased by 250% and 300% compared to control rats, but formations of androstenedione and 6β-hydroxytestosterone were significantly decreased. The formations of 16α-hydroxytestosterone and 7α-hydroxytestosterone were unaltered [141]. Induction of CYP2E1, 4A2 and K-4 as well as increases in omega-and (omega-1) hydroxylation of lauric acid were also observed in kidney of STZ-induced rats [26].…”

Section: Cyp450mentioning

confidence: 88%

“…Induction of CYP2E1, 4A2 and K-4 as well as increases in omega-and (omega-1) hydroxylation of lauric acid were also observed in kidney of STZ-induced rats [26]. Insulin treatment partly reversed these alterations by diabetes [26,141]. However, a recent report showed that expression of CYP4A protein in diabetic mice induced by HFD/STZ was downregulated by 29.16% of control mice [142].…”

Section: Cyp450mentioning

confidence: 97%

Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance

Yang

¹

,

Liu

²

2020

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The pharmacokinetics of a drug is dependent upon the coordinate work of influx transporters, enzymes and efflux transporters (i.e., transporter-enzyme interplay). The transporter–enzyme interplay may occur in liver, kidney and intestine. The influx transporters involving drug transport are organic anion transporting polypeptides (OATPs), peptide transporters (PepTs), organic anion transporters (OATs), monocarboxylate transporters (MCTs) and organic cation transporters (OCTs). The efflux transporters are P-glycoprotein (P-gp), multidrug/toxin extrusions (MATEs), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). The enzymes related to drug metabolism are mainly cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyltransferases (UGTs). Accumulating evidence has demonstrated that diabetes alters the expression and functions of CYP450s and transporters in a different manner, disordering the transporter–enzyme interplay, in turn affecting the pharmacokinetics of some drugs. We aimed to focus on (1) the imbalance of transporter-CYP450 interplay in the liver, intestine and kidney due to altered expressions of influx transporters (OATPs, OCTs, OATs, PepTs and MCT6), efflux transporters (P-gp, BCRP and MRP2) and CYP450s (CYP3As, CYP1A2, CYP2E1 and CYP2Cs) under diabetic status; (2) the net contributions of these alterations in the expression and functions of transporters and CYP450s to drug disposition, therapeutic efficacy and drug toxicity; (3) application of a physiologically-based pharmacokinetic model in transporter–enzyme interplay.

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“…In STZ-induced diabetic rats, formations of hydroxyandrostenedione and 2α-hydroxytestosterone were significantly increased by 250% and 300% compared to control rats, but formations of androstenedione and 6β-hydroxytestosterone were significantly decreased. The formations of 16α-hydroxytestosterone and 7α-hydroxytestosterone were unaltered [141]. Induction of CYP2E1, 4A2 and K-4 as well as increases in omega-and (omega-1) hydroxylation of lauric acid were also observed in kidney of STZ-induced rats [26].…”

Section: Cyp450mentioning

confidence: 99%

“…Induction of CYP2E1, 4A2 and K-4 as well as increases in omega-and (omega-1) hydroxylation of lauric acid were also observed in kidney of STZ-induced rats [26]. Insulin treatment partly reversed these alterations by diabetes [26,141]. However, a recent report showed that expression of CYP4A protein in diabetic mice induced by HFD/STZ was downregulated by 29.16% of control mice [142].…”

Section: Cyp450mentioning

confidence: 99%