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Atorvastatin up-regulates the expression and activity of renal Cytochrome P450 3A2 in diabetic rats

Hassan Malekinejada, Shahin Alizadeh-Fanalou, Rahim Hobbenaghi, Shirin Rokhsartalb-Azar

. 2016 ; 14 (1) : 25-34.

Jazyk angličtina Země Česko

Perzistentní odkaz   https://www.medvik.cz/link/bmc16015198

Effects of atorvastatin on the expression of Cytochrome P450 3A2 and its enzymatic activity in the kidney of diabetic rats were investigated. Diabetes was induced by injection of streptozotocine (50 mg/kg, b.w., i.p.) in male Wistar rats. The animals were assigned into four groups including control (C), non-treated diabetic (D), atorvastatin-treated diabetic (AD) and atorvastatin-treated non-diabetic (A) groups. Metabolism of testosterone was examined in the presence of renal microsomes. The expression of CYP 3A2 at mRNA level was examined by means of PCR technique. The atorvastatin administration resulted in a remarkable improvement of diabetes-induced nephropathy and oxidative stress. Enzyme kinetics analyses showed that both diabetic groups produced significantly (P < 0.05) more 6β-hydroxytestosterone (Vmax for D = 34.7 ± 1.3 and for AD = 45.1 ± 2.3 pM/min/mg) than that of the control group (Vmax = 21.6 ± 1.5 pM/min/mg). Both diabetes and atorvastatin administration resulted in a significant up regulation of CYP 3A2 mRNA level in the kidney. Our data suggest that due to profound influence of diabetes and atorvastatin on renal metabolism of CYP 3A2 substrate and up-regulation of this gene, there should be adjusted dose regimen for medications which are classified as CYP 3A2 substrates.

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Literatura

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$a Malekinejada, Hassan $u Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran; Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Urmia University, Iran
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$a Effects of atorvastatin on the expression of Cytochrome P450 3A2 and its enzymatic activity in the kidney of diabetic rats were investigated. Diabetes was induced by injection of streptozotocine (50 mg/kg, b.w., i.p.) in male Wistar rats. The animals were assigned into four groups including control (C), non-treated diabetic (D), atorvastatin-treated diabetic (AD) and atorvastatin-treated non-diabetic (A) groups. Metabolism of testosterone was examined in the presence of renal microsomes. The expression of CYP 3A2 at mRNA level was examined by means of PCR technique. The atorvastatin administration resulted in a remarkable improvement of diabetes-induced nephropathy and oxidative stress. Enzyme kinetics analyses showed that both diabetic groups produced significantly (P < 0.05) more 6β-hydroxytestosterone (Vmax for D = 34.7 ± 1.3 and for AD = 45.1 ± 2.3 pM/min/mg) than that of the control group (Vmax = 21.6 ± 1.5 pM/min/mg). Both diabetes and atorvastatin administration resulted in a significant up regulation of CYP 3A2 mRNA level in the kidney. Our data suggest that due to profound influence of diabetes and atorvastatin on renal metabolism of CYP 3A2 substrate and up-regulation of this gene, there should be adjusted dose regimen for medications which are classified as CYP 3A2 substrates.
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