Hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity in rats

Objectives: Several studies demonstrated the antioxidant and anti-inflammatory role of melatonin and celecoxib. This study is designed to explore the underlying mechanism of hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity by morphological, and biochemical approaches. Materials and methods: Adult male rats were divided into five groups: saline, ethanol, melatonin, and celecoxib were administered for 11 consecutive days after ethanol injection. Biochemical analyses were performed for the determination of glutathione (GSH), glutathione S-transferase (GST), and inducible nitric oxide (iNOS). Immunohistochemistry was performed to determine the level of different inflammatory markers. Results: Histopathological results showed that ethanol-induced marked hepatic injury leads to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all hepatic zones. Biochemical analysis revealed significant increases in serum transaminases and alkaline phosphatase in the ethanol group. Oxidative stress associated with attenuated antioxidant enzymes was also spotted in the ethanol group, as ethanol down-regulated GSH, GST, and upregulated NO. Additionally, ethanol increased the activation and the expression of tumor necrotic factor (TNF-alpha), p-NFKB, and COX2. Finally, hepatic cellular apoptosis was clearly obvious in ethanol intoxicated animals using activated JNK staining. Conclusion: These results provided pieces of evidence that the hepatoprotective effect of melatonin and celecoxib is possibly mediated through the modulation of JNK and TNF-alpha signaling pathways with subsequent suppression of inflammatory and apoptotic processes.