Protective effects of caffeic acid phenylethyl ester, a main component of propolis against cyclosporine A-induced nephrotoxicity in rats

ABSTRACT

The present study was designed to investigate the possible protective effects of Caffeic acid phenylethyl ester [CAPE] against Cyclosporine A [C5A] induced nephrotoxicity in rats. Through antioxidant, free radical scavenger and anti-inflammatory effects of CAPE and CsA. Thirty two male Sprague-Dawley rats were divided into four groups of eight rats in each one; first group served as control [treated with vehicle]. The other groups were treated intraperitoneally with CsA alone [20 mg/kg/24 hours], CAPE alone [10 micro mol/kg/24 hours] and CAPE plus CsA for 21 days. The treatment with CAPE started two days before the first dose of CsA. Estimation of urine volume, serum creatinine and urea concentrations, creatinine clearance, kidney tissue malondialdehyde [MDA] and glutathione [GSH] contents were carried out after the last dose of CsA. Also, the lysosomal enzymes [N-acetyl-beta-glucosaminidase [NAG] and beta-glucuronidase [beta-GLU]] and antioxidant enzymes [glutathione peroxidase [GSH-Px], catalase [CAT] and superoxide dismutase [SOD]] activities were estimated in kidney homogenates. Kidneys were also examined for histological changes. CsA caused a marked nephrotoxicity as evidenced by significant increases in urine volume [295%], serum creatinine [194%] and urea [167%] and a significant decrease in creatinine clearance [Ccr] [24%]. Pre-treatment with CAPE produced amelioration in biochemical indices of nephrotoxicity in serum and urine. Furthermore, CAPE prevented the CsA-induced increase in the renal levels of oxidative stress markers [MDA, NAG and beta-GLU] and prevent the decrease in the antioxidant enzymes [SOD, CAT and GSH-Px] activities. In addition, co-administration of CAPE was found to reduce the degree of kidney tissue damage in histopathological findings. CAPE as a natural antioxidant might have protective effects against CsA-induced nephrotoxicity and oxidative stress in rats. However, clinical studies are warranted to investigate such an effect in human subjects: