| Summary: | Abstract Background Dennentia tripetalla (Pepper Fruit) belongs to the Annonaceae family and is abundant in Nigeria. Its fruit in folklore medicine is used for treatment of varying ailments. While ample research evidence exists on the plants fruit and seed, no current study exists on the toxicological profile of the plant leaves. Methods qualitative and quantitative phytochemicals and In vitro antioxidant assays were carried out using standard methods. The acute toxicity study indicates that the LD50 was higher than 2000 mg/Kg body weight. Sub-chronic toxicity studies was carried out using five groups of rats. Group 1 served as control, 2–5 received 100 mg/Kg, 200 mg/Kg, 500 mg/Kg and 1000 mg/Kg body weight orally for 28 days. Results Post-administration biochemical analysis indicates there was increased weight in rats administered 100 mg/kg and 200 mg/kg while it reduced in the 500 mg/kg group. Significant elevations of liver function markers were reported for 200 mg/kg and 500 mg/kg respectively. Serum and hepatic protein profiles remained unaltered. Renal function analysis revealed elevated serum urea and creatinine for 200 and 500 mg/kg groups, elevated serum Na+ and Ca+ and reduced serum Cl− for the 500 mg/Kg group. Elevated Kidney K+ and Ca+ levels, reduced Cl− were significantly observed in 500 mg/Kg group. Significant rise in hepatic and renal lipid peroxidation was observed in 200 and 500 mg/Kg groups. There were observed disarmament of the antioxidant defense systems occasioned by rise and drop in tissue (hepatic, renal, testes, heart) Superoxide dismutase (SOD), Catalase (Cat), Glutathione-s-transferase (GST), Glutathione peroxidase (GPx) activities in the test groups relative to control. Histopathological examination indicated architectural aberrations at 500 and 1000 mg/kg. Conclusions It concluded that the plant had significant phytochemical and antioxidant properties of medical interest and possessed toxic properties in rats when administered at a dose above 200 mg/Kg over a prolonged period of time.
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