The protective effect of 7-hydroxycoumarin against cisplatin-induced liver injury is mediated via attenuation of oxidative stress and inflammation and upregulation of Nrf2/HO-1 pathway

Cisplatin (CIS) is an effective chemotherapy against different solid cancers. However, the adverse effects, including hepatotoxicity, limit its clinical use. 7-hydroxycoumarin (7-HC) possesses antioxidant and hepatoprotective activities, but its protective effect against CIS hepatotoxicity has not been investigated. This study evaluated the effect of 7-HC on liver injury, oxidative stress (OS), and inflammation provoked by CIS. Rats received 7-HC (25, 50, and 100 mg/kg) orally for 2 weeks followed by intraperitoneal injection of CIS (7 mg/kg) at day 15. CIS increased serum transaminases, alkaline phosphatase (ALP), and bilirubin and provoked tissue injury accompanied by elevated reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO). Liver nuclear factor (NF)-κB p65, inducible NO synthase (iNOS), pro-inflammatory cytokines, Bax, and caspase-3 were upregulated, and antioxidant defenses and Bcl-2 were decreased in CIS-treated rats, while 7-HC prevented liver injury and ameliorated OS, inflammatory and apoptosis markers. In addition, 7-HC enhanced nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase (HO)-1 in CIS-administered rats and in silico studies revealed its binding affinity toward HO-1. In conclusion, 7-HC protected against CIS hepatotoxicity by mitigating OS and inflammatory response and modulating Nrf2/HO-1 pathway

An integrated phytochemical, in silico and in vivo approach to identify the protective effect of Caroxylon salicornicum against cisplatin hepatotoxicity

Cisplatin (CIS) is a chemotherapeutic medication for the treatment of cancer. However, hepatotoxicity is among the adverse effects limiting its use. Caroxylon salicornicum is traditionally used for treating inflammatory diseases. In this investigation, three flavonoids, four coumarins, and three sterols were detected in the petroleum ether fraction of C. salicornicum (PEFCS). The isolated phytochemicals exhibited binding affinity toward Keap1, NF-κB, and SIRT1 in silico. The hepatoprotective role of PEFCS (100, 200 and 400 mg/kg) was investigated in vivo. Rats received PEFCS for 14 days and CIS on day 15. CIS increased ALT, AST and ALP and caused tissue injury along with increased ROS, MDA, and NO. Hepatic NF-κB p65, pro-inflammatory mediators, Bax and caspase-3 were increased in CIS-treated animals while antioxidants and Bcl-2 were decreased. PEFCS mitigated hepatocyte injury, and ameliorated transaminases, ALP, oxidative stress (OS) and inflammatory markers. PEFCS downregulated pro-apoptosis markers and boosted Bcl-2 and antioxidants. In addition, PEFCS upregulated Nrf2, HO-1, and SIRT1 in CIS-administered rats. In conclusion, PEFCS is rich in beneficial phytoconstituents and conferred protection against liver injury by attenuating OS and inflammation and upregulating Nrf2 and SIRT1