Abstract:

Objective: To investigate the protective effect and possible mechanisms of grape seed proanthocyanidin extract
(GSPE) against cisplatin (CDDP)-induced nephrotoxicity in mice. Methods: A total of 60 adult male mice were randomly
divided into control group, CDDP model group, GSPE + CDDP pretreatment group and GSPE + CDDP co-administration
group. The blank control, CDDP model and GSPE + CDDP co-administration groups were fed a normal diet and orally
administered with distilled water during the administration period, while the GSPE + CDDP pretreatment group with GSPE
at 200 mg/(kg•d) for 12 consecutive days. After administration for 10 days, the blank control group was given normal saline
by intraperitoneal injection while a single injection of CDDP (20 mg/kg) in the remaining groups was carried out to establish
mouse model of renal injury. At the end of the administration period (13th day), all mice were sacrificed to determine serum
blood urine nitrogen (BUN) and serum creatinine concentration (Scr) contents, superoxide dismutese (SOD), glutathione
peroxidase (GSH-Px) and nitric oxide synthase (NOS) activities, and malonaldehyde (MDA) and nitrogen oxide (NO)
contents. Results: The GSPE pretreatment group could significantly inhibit the CDDP-induced inactivation of antioxidant
enzymes (SOD and GSH-Px) and the increase in serum blood urine nitrogen (BUN) and serum creatinine concentration
(Scr) contents as well as the levels of lipid peroxide (MDA, NO and NOS) in renal tissues of mice (P ＜ 0.05 or P ＜ 0.01),
and these effects were better than those observed for the GSPE + CDDP co-administration group. Conclusion: GSPE has a
protective effect on CDDP-induced nephrotoxicity in mice. The possible mechanism is associated with the fact that GSPE
can decrease the contents of lipid peroxide, and can increase the antioxidant enzyme activities.

Key words: grape seed proanthocyanidin extract (GSPE), cisplatin, nephrotoxicity, protective effect