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

• Atorvastatin lowered the diabetes-induced oxidative and nitrosative stress.
• Diabetes and atorvastatin both induced the Cytochrome 3A2 enzymatic activities in the renal tissue.
• Atorvastatin attenuated the diabetes-induced damages in the kidneys.
• Diabetes and atorvastatin both up-regulated the expression of Cytochrome 3A2 in renal tissue.

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.

Atorvastatin and diabetes both induce the Cytochrome P-450 3A2 in the kidneys of rats.Figure optionsDownload as PowerPoint slide