Effect of Celtis occidentalis L. extract on induced nephrotoxicity by mitigating inflammation, oxidative stress, and nephrotoxic nephritis in rabbits

Paracetamol is a widely used analgesic and antipyretic medication; however, excessive use can lead to toxic effects in humans, including nephrotoxicity. Herein, we aimed to investigate the paracetamol-induced nephrotoxicity in rats and explore the potential of a methanolic extract of Celtis occidentalis leaves as a remedy. The experimental animal groups (n = 8, 5 animals each) were given oral doses of paracetamol, extract and silymarin, once a day after 12 h of fasting. All animals were sacrificed after 21 days of experimental cycle. Results demonstrated that paracetamol overdoses have elevated the serum levels of creatinine, urea, and uric acid, and have caused oxidative stress evident from malondialdehyde (MDA) elevated levels, and decreased levels of the tested antioxidant enzymes. A significant decline was observed in serum biomarkers compared to the paracetamol (PCM) group. The methanolic extract of C. occidentalis leaves attenuated the oxidative stress due to decreasing MDA and enhancing the level of antioxidant enzymes (SOD and GSH). Additionally, it reduced inflammation by lowering cytokine levels. The extract also led to significant reductions (p < 0.01 and p < 0.001) in the elevated serum levels of creatinine, urea, and uric acid. Paracetamol causes severe changes in renal histology, inflammatory cell infiltration, degeneration of the tubular epithelium, glomerular congestion, and parenchymal tissue haemorrhage. However, the extract of Celtis occidentalis mitigated these alterations, showing results similar to those observed in the control group. These findings suggest Celtis occidentalis has strong nephroprotective potential, primarily enhancing the antioxidant defense system and reducing inflammatory and oxidative stress in the kidneys. Thus, it could be considered a promising candidate for future drug development.