Comparison of the Effects of Vitamin E and/or Quercetin in Attenuating Chronic Cyclosporine A‐induced Nephrotoxicity in Male Rats

Abstract

1. The aim of the present study was to investigate the effects of vitamin E and/or quercetin (Q) on renal function, oxygen radical concentrations in the kidney and some anti-oxidant enzyme activities in rats treated with cyclosporine A (CsA). 2. Groups of rats (270 +/- 15 g), on standard rat chow and water, received all their treatments by gavage for either 4 or 8 weeks. Control groups received either olive oil (0.5 mL) or 25% ethanol (0.5 mL) + olive oil (0.5 mL) per day as vehicle. All experimental groups received 25 mg CsA/kg per day in 0.5 mL olive oil. The vitamin E group received 100 mg vitamin E/kg per day in olive oil in addition to CsA treatment. The quercetin group received 15 mg of Q/kg per day in 0.5 mL of 25% ethanol in addition to CsA treatment. The vitamin E + quercetin group received the two anti-oxidants at the concentrations given in addition to CsA treatment. 3. Quercetin, at a concentration less than one-quarter of vitamin E, was more efficient in lowering blood urea nitrogen, serum creatinine and kidney malondialdehyde in CsA-treated rats. However, neither of the two anti-oxidants was able to normalize these analytes to control values after either 4 or 8 weeks treatment. 4. Quercetin (50 micromol/kg per day) elevated all renal anti-oxidant enzyme activities to values observed in the negative controls. However, vitamin E (232 micromol/kg per day) only normalized glutathione peroxidase activity at the end of either 4 or 8 weeks treatment. Combination treatment with the two anti-oxidants abolished all the ill-effects of CsA. 5. Combination treatment with the two anti-oxidants of renal transplant patients receiving CsA may be beneficial in ameliorating the chronic nephrotoxic effects of the important immunosuppressive drug CsA.

Effect of Reduced Form of Coenzyme Q10 on Cyclosporine Nephrotoxicity

“…Several previous studies had suggested that cyclosporine nephrotoxicity may be improved or prevented by antioxidants. [12][13][14][15][16][17] A meta-analysis of clinical trials of CoQ10 for hypertension concluded that CoQ10 had potential for lowering blood pressure in hypertensive patients 18 ; however, in this study, no significant reduction of systolic blood pressure was observed when rCoQ10 was administered with cyclosporine. A possible explanation for this finding is that cyclosporine-induced hypertension may be caused by activation of the intrarenal renin-angiotensin axis, 7 but the renal protective effect of rCoQ10 may be accomplished by another mechanism.…”

Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

“…27 In a study performed on nephrotoxic rats, both vitamin E and quercetin improved renal function to some extent, but it was the combination of the two that lowered the blood urea nitrogen (BUN) and creatinine levels to those seen in HCs. 16 The effect of milk thistle extract and silymarin on kidney SOD level was somehow unexpected in this study. None of the treatments could make a significant increase in SOD level compared to the DC group (Table 2).…”

“…Kidney homogenate was prepared according to the procedure of Zal et al 16 The clear supernatant obtained upon centrifugation was kept at −70°C until used for the estimation of thiobarbituric acid reactive species (TBARS), and for the measurement of the activities of Cu, Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) enzymes.…”

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity

“…RCoQ10 also diminished TGF-beta expression in the proximal renal tubular cells. There are several animal and clinical studies suggesting that antioxidative agents have some preventive effect of CyA nephrotoxicity (7)(8)(9)(10)(11)(12). In 2004, Dlugosz et al reported the benefit of CoQ10 on renal transplant recipients for the first time (13); however, they used ubiquinone, the oxidized form of CoQ10.…”