Impact of Melatonin on Sepsis-Associated Acute Kidney Injury in Rat Model of Lipopolysaccharide Endotoxemia

Sepsis-associated acute kidney injury (S-AKI) is a frequent and life-threatening condition, characterized by rapid functional decline, which is followed by intense inflammation and tissue injury. Experimental lipopolysaccharide (LPS)-induced sepsis reproduces functional and morphological features of human S-AKI and enables investigation of melatonin which has numerous beneficial properties, such as antioxidant properties. In this study, the effects of melatonin (50 mg/kg) on kidney dysfunction, oxidative damage, inflammation, apoptosis, and histopathological alterations in a rat model of S-AKI induced by LPS application (10 mg/kg) were studied. Acute LPS exposure caused statistically significant (<i>p</i> ≤ 0.05) marked renal dysfunction, increased lipid and protein oxidation, suppression of antioxidant enzymes, enhanced NO/iNOS signaling, elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), activation of apoptotic pathways, and pronounced tubular and glomerular injury. Co-administration of melatonin statistically significantly (<i>p</i> ≤ 0.05) attenuated oxidative stress, reduced production of inflammatory cytokines, suppressed apoptosis, and ameliorated structural kidney damage, leading to partial restoration of renal function. These findings suggest that melatonin exerts renoprotective effects in S-AKI through combined antioxidant, anti-inflammatory, and anti-apoptotic actions, likely involving modulation of different signaling pathways.