Lycopene Mitigates Rat Liver Damage Induced by Lipopolysaccharide via Mechanisms Involving Oxidative Stress, Inflammation, and Apoptosis.

BACKGROUND

Sepsis is a leading cause of mortality in intensive care units, with liver dysfunction representing a critical determinant of poor outcome, mainly associated with excessive inflammation and oxidative stress. Lycopene, a carotenoid with potent antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study investigated whether lycopene supplementation mitigates lipopolysaccharide-induced oxidative and inflammatory liver injury in rats.

METHODS

Male Wistar rats, divided into four groups, were exposed to either lipopolysaccharide or a combination of lipopolysaccharide (10 mg/kg) and lycopene (6 mg/kg). In order to assess liver damage induced by lipopolysaccharide, hepatocellular injury markers, oxidative stress indices, nitric oxide metabolism, glutathione redox status, apoptotic enzyme activity, and inflammatory mediators were assessed in serum and liver tissue.

RESULTS

Lipopolysaccharide induced marked hepatocellular damage, characterized by elevated serum liver-cell damage parameters, and liver tissue xanthine oxidase, myeloperoxidase, thiobrabituric reactive substances, protein carbonyl content, deoxyribonuclease I/II activity, nuclear factor kappa B, tumor necrosis factor-α, and interleukin-6, alongside depletion of reduced glutathione and reduced glutathione reductase and glutathione peroxidase activities. Lyc pretreatment significantly attenuated liver enzyme leakage, oxidative damage, and cytokine release while restoring reduced glutathione and glutathione reductase activity. In contrast, lycopene had limited effects on glutathione peroxidase activity, nitric oxide/inducible nitric oxide synthase signaling, and nuclear factor erythroid 2-related factor 2 expression.

CONCLUSIONS

These findings demonstrate that lycopene confers partial hepatoprotection in endotoxemic rats, primarily through suppression of oxidative damage and nuclear factor kappa B-mediated inflammation. Further studies are needed to clarify tissue-specific mechanisms and optimize dosing strategies in order to increase the efficacy of this carotenoid.