The Influence of Celtis occidentalis L. Extract on Acetaminophen-Induced Nephrotoxicity by Mitigating Inflammation, Oxidative Stress, and Nephrotoxic Nephritis in Rabbits

Background: Paracetamol is a commonly available drug used as an analgesic and antipyretic. With or without a prescription, overdose can lead to severe complications such as hepatotoxicity, nephrotoxicity, and acute pancreatitis.Objective: This research aims to assess the antioxidant, anti-inflammatory, and renoprotective effects of the methanolic extract (met. ext.) of Celtis occidentalis leaves on paracetamol-induced nephrotoxicity in rabbits.Methods: Forty male rabbits (Oryctolagus cuniculus) were divided into eight groups, each comprising five individuals (n = 5). Groups I, II, III, IV, V, VI, VII, and VIII are the control, paracetamol (PCM) (2 g/kg), met. ext. (200 mg/kg), PCM (2 g/kg) + silymarin (50 mg/kg), silymarin (50 mg/kg), PCM (2 g/kg) + met. ext. (100 mg/kg), PCM (2 g/kg) + met. ext. (200 mg/kg), and PCM (2 g/kg) + met. ext. (300 mg/kg) groups, respectively. These elements were administered orally once a day after 12 hours of fasting. All animals were dissected after 21 days of experimentation.Results: Results demonstrate that paracetamol overdoses elevated the serum levels of creatinine, urea, and uric acid, caused oxidative stress by increasing the malondialdehyde (MDA) level, and decreased the antioxidant enzyme concentrations (total glutathione and superoxide dismutase). A significant decline in serum biomarkers was observed when treated with the met. ext. of C. occidentalis leaves as compared to the PCM group. The met. ext. of C. occidentalis leaves attenuated oxidative stress by decreasing MDA levels and enhancing antioxidant enzyme levels. It also ameliorated inflammation by decreasing the cytokine levels (IFN-γ and TNF-α). Paracetamol caused dramatic changes in renal histology, including inflammatory cell infiltration, degeneration of the tubular epithelium, glomerular congestion, and parenchymal tissue hemorrhage. These alterations were mitigated by C. occidentalis, as found in the control group.Conclusion: These findings suggest that C. occidentalis has strong nephroprotective potential, primarily enhancing the antioxidant defense system and reducing inflammatory and oxidative stress in the kidney. However, further research and clinical trials are needed to identify various active compounds for testing in future studies.