Melatonin arrests excessive inflammatory response and apoptosis in lipopolysaccharide-damaged rat liver: A deeper insight into its mechanism of action.

Abstract

Sepsis is a life-threatening organ dysfunction. An animal model mimicking sepsis utilizes lipopolysaccharide (LPS), an endotoxin recognized as the most potent bacterial mediator of sepsis. Melatonin (MLT), an effective anti-inflammatory and antioxidant agent, is a promising adjunctive drug for sepsis. This study aimed to estimate the potential of MLT in preventing LPS-induced liver damage in Wistar rats by determining the levels of serum and tissue biochemical markers that reflect liver state and function, i.e., serum levels of transaminases and albumin, as well as a panel of oxidative stress-related biomarkers. Additionally, a pathohistological analysis of liver tissue was conducted. Pre-treatment with MLT prevented an LPS-induced increase in serum and tissue liver damage markers and a decrease in the tissue antioxidant capacity, in both enzymatic and non-enzymatic systems. Micromorphological liver tissue changes mirrored the alterations observed in the biochemical status. In rats with LPS-induced sepsis, melatonin was shown to be a crucial antioxidant and anti-inflammatory agent, with vital roles in the alleviation of oxidative stress, causing an increase of the antioxidant capacities and the improvement of the liver's microscopic appearance.