Hepatoprotective actions of melatonin by mainly modulating oxidative status and apoptosis rate in lipopolysaccharide-induced liver damage

Abstract

Aim

One of the serious complications of sepsis is liver damage and liver failure. This study aimed to evaluate the protective and therapeutic potential of melatonin in rats with lipopolysaccharide-induced sepsis.

Main methods

Female Spraque–Dawley rats received single a dose of 7.5 mg/kg lipopolysaccharide in saline to create a 24-h sepsis model. One of the other groups received melatonin at a dose of 10 mg/kg/day beginning 1 week before sepsis induction to the end of the experiment. The melatonin group received the same doses of melatonin for the same duration but not lipopolysaccharide. The vehicle group received the same doses of saline, the vehicle of melatonin, for the same duration. Twenty-four hours after the last injection, the rats were decapitated. By appropriate histochemical, immunohistochemical, biochemical, and molecular techniques, anti-necrotic, anti-apoptotic, anti-necroptotic, anti-inflammatory, and antioxidant effects of melatonin were assessed.

Key findings

Lipopolysaccharide has disrupted liver functions by inducing oxidative stress, inflammation, necrotic, apoptotic, and necroptotic cell death, thus disrupting liver functions. Melatonin was found to be beneficial in terms of inhibiting the intrinsic pathway of apoptosis and tissue oxidant levels, stimulating tissue antioxidant enzyme levels, and restoring hepatocyte functions.

Significance

Melatonin, at those doses and duration, was found to be hepatoprotective by mainly modulating oxidative status and apoptosis rate, however, failed to significantly reduce histopathological damage. We suggest that longer-term melatonin administration may produce anti-inflammatory and anti-necrotic effects as well.

Keywords:

• Apoptosis
• necrosis
• necroptosis
• liver
• melatonin
• oxidative stress

Author contributions

Study conception and design: M.E. and A.H.Y. Animal experiments: T.K.K. Data collection: T.K.K., F.B.K.-C., and E.R.H. Analysis and interpretation of results: M.E., B.E., and E.K. Draft manuscript preparation: M.E. All authors reviewed the results and approved the final version of the manuscript.

Ethical approval

Approval for the study was granted by Bezmialem Vakıf University Local Ethics Committee for Animal Experiments (Ethic Committee No. 2018/131).

Disclosure statement

The authors have no conflicts of interest to disclose.

Data availability statement

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

The project was supported by the Scientific Research Unit of Bezmialem Vakıf University (BAP No. 11.2018/25).