Melatonin alleviates cisplatin induced liver toxicity in rats by up-regulation of Nrf2/HO-1 signaling pathway

Background: One of the most well-known chemotherapy drugs is cisplatin (Cis). Hepatotoxicity is among the most significant adverse effects of cisplatin. The pineal gland hormone melatonin (Mel) is primarily reliant on the light/dark cycle for its cyclic release. This neurohormone can preserve tissue redox equilibrium and functions as an antioxidant.Aim: The purpose of the study was to assess hepatoprotective impact of Mel in rats exposed to Cis, as well as any possible underlying processes.Methods: Three groups of thirty adult male albino rats were created: control, Cis, and Cis+Mel. Hepatic MDA, hepatic SOD, hepatic TNF-α, hepatic IL-6, hepatic IL-10, liver-expressed Nrf2 and HO-1 genes and serum liver enzymes were measured. Additional assessments of the liver's caspase-3 and NF-kB immunoreaction were conducted.Results: Hepatic SOD, IL-10, and Nrf2 and HO-1 gene expression all significantly decline in response to cis-induced damage. Nevertheless, as compared to control, there was a notable rise in serum liver enzymes along with hepatic MDA, TNF-α, and IL-6, along with an upregulation of caspase-3 and NF-kB immunoreaction in the liver. Mel significantly improved the liver abnormalities brought on by Cis.Conclusion: Mel employed anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms in addition to up-regulating the Nrf2/HO-1 signaling cascade to reduce the hepatotoxicity brought on by Cis.