Anti-apoptotic effect of vinpocetine on cisplatin-induced hepatotoxicity in mice: The role of Annexin-V, Caspase-3, and Bax.

Hepatic damage is one of the most common complications related to cisplatin (Cis) use. Recently, liver protection lines are being discovered to avoid hepatic cell death as a result of oxidative, inflammatory, and apoptotic disturbance. Limited data reported the hepatoprotective effect of vinpocetine (Vin) in acute liver injury models. This study was designed to determine the potential protective effect of Vin (10-30 mg/kg, orally) against Cis-induced liver injury (10 mg/kg, IP) in mice. Vin administration for 1 week before Cis injection until the end of the experiment. On the 6th day after Cis injection, mice were anesthetized, blood and tissue samples were collected. Hepatic function, histological changes, oxidative stress, inflammation, and apoptotic markers were investigated. Vin administration ameliorated liver injury as indicated by decreased liver injury parameters; serum aminotransferases, ALK-P, GGT, and bilirubin, restored the anti-oxidant status by decrease MDA and NOx , and increased GSH and SOD, inhibited inflammation (IL-6, TNF-α, NFκB-p65, and iNOS) and apoptosis (Annexin-V, Bax, and Caspase-3) parameters. Vin confers dose-dependent protection against Cis-induced liver injury. The hepatoprotective effect of Vin involved anti-oxidative, anti-inflammatory, and anti-apoptotic activities.

The protective effect of protocatechuic acid on hepatotoxicity induced by cisplatin in mice.

Cisplatin is one of the most potent anti-cancer drugs used for the treatment of various solid tumors, yet it has several side effects that may limit its clinical use. Hepatotoxicity is one of the most serious side effects as it may lead to liver failure. Several mechanisms including oxidative stress, inflammation, and apoptosis have been examined in cisplatin-induced hepatotoxicity. Protocatechuic acid (Proto) which is naturally occurring phenolic acid has shown different biological activity as antioxidant, anti-inflammatory, and anti-apoptotic. In this study, we investigate the protective effect of Proto at two doses 100 and 150 mg/kg on hepatotoxicity induced by a single injection of 10 mg/kg cisplatin in female albino mice. The present study demonstrates for the first time that Proto administration (100 and 150 mg/Kg) significantly attenuates cisplatin-induced changes in liver function [increase serum albumin and decrease liver injury markers ALT, AST, GGT, and bilirubin]. This was associated with marked hepatic antioxidant effects [decrease MDA and NO levels, increase GSH and SOD activity]. Moreover, Proto reduced cisplatin-induced apoptosis in the liver through decreasing caspase-3, annexin-V, and BAX. Both doses suppressed cisplatin-induced expression of iNOS and NF-ᴋB p65 subunit and pro-inflammatory cytokines (IL-6 and TNF-α). Also, Proto improved histopathological examination of the liver. The present findings reveal that the antioxidant, anti-inflammatory, and anti-apoptotic effects of Proto are the main mechanisms by which Proto can ameliorate cisplatin-induced liver injury.