EFFECTS OF SYRINGIC ACID ON CISPLATIN-INDUCED HEPATOTOXICITY IN MALE WISTAR RATS

Cisplatin (CISP) is a chemotherapeutic drug used to treat various solid cancers. Its limitation in terms of usage is due to different toxic side effects it presents. Consequently, the need to source for another drug candidate that can be co-administered with it to eliminate the various toxic side effects is essential. In this study, we chose syringic acid (SAC) as that drug candidate following its outstanding performance compared with known inhibitors or activators in the computational/molecular docking study and investigated its prophylactic and therapeutic effects on cisplatin-induced hepatotoxicity in male Wistar rats. In the prophylactic group, 50 mg/kg of SAC was orally administered consecutively for 14 days followed by intraperitoneal injection of 5 mg/kg of CISP twice in 5 days, while in the therapeutic group, CISP was administered first, followed by SAC, as done for the prophylactic group. Following analyses, CISP-induced hepatotoxicity was marked by a significant elevation in the serum activities of AST and ALT, hepatic levels of H2O2, MDA, GSH, PI3K, and hepatic activities of SOD, GPx, and CAT, and reduction in hepatic levels of Akt/PKB, Nrf2, IL-6, and activity of GST compared with the control group. SAC, in the form of a prophylactic or therapeutic agent reversed the effects of CISP-induced hepatotoxicity. It is concluded that the efficacy of SAC to prevent or treat CISP-induced hepatotoxicity can be linked to its strong antioxidant property and ability to modulate the PI3K-Akt/PKB signaling pathway.