Effects of Caffeic acid phenethyl ester (CAPE) and/or PD98059 (PD) on the gene expression of Caveolin-1 (CAV1) and reduced glutathione (GSH), malondialdehyde (MDA), copper-zinc superoxide dismutase (CuZn-SOD), and catalase (CAT) enzyme activities were investigated in an experimental chronic renal failure model in rats. Eighty Wistar rats were divided into eight groups for a 28-day study: Control, CsA (Cyclosporine A), CsA-V (CsA solvent), CsA + PD (CsA + PD98059), CsA + PD + CAPE, CsA + CAPE, CAPE-V (CAPE solvent), and PD-V (PD98059 solvent). Serum blood urea nitrogen and creatinine levels, as well as histopathological findings indicated the development of renal failure in the CsA group. Kidney GSH levels decreased while MDA levels, CuZn-SOD, and CAT activities increased significantly in the CsA group compared to control indicating oxidative stress. CAV1 gene expression significantly decreased in the CsA group compared to the control. PD98059 and CAPE applications made positive improvements in the levels of the parameters investigated. PD98059 and CAPE applications in CsA given animals increased GSH and CAV1 gene expressions and decreased CuZn-SOD and CAT levels compared to the CsA group. In conclusion, it was shown that PD98059 and CAPE could attenuate the effects of chronic renal failure, and CAV1 is suggested as a therapeutic target and the inhibition of the p44/42 MAPK pathway may be a new approach for the treatment of renal degenerations.
Keywords: CAPE; Chronic renal failure; PD98059; caveolin; cyclosporine A.