Abstract
Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride (AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10 mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10 mg/kg b.w./day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3-treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3-induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3-treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3-triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.