Ziziphus abyssinica root bark extract ameliorates paracetamol-induced liver toxicity in rats possibly via the attenuation of oxidative stress

Abstract

Ziziphus abyssinica root bark is widely used in folk medicine to manage liver diseases, particularly, jaundice but its effect on paracetamol-induced liver toxicity (PILT) has not yet been validated. This study explored the ameliorative effect of ethanolic root bark extract of Ziziphus abyssinica (ZAE) against PILT in rats. The flavonoid and phenolic content of ZAE was evaluated using Folin-Ciocalteau and aluminium trichloride colorimetric methods, respectively. Antioxidant activity of ZAE was determined in vitro by evaluating its ferrous reducing antioxidant capacity (FRAC) as well as DPPH and nitic oxide (NO) radicals scavenging activities. Sprague-Dawley rats were assigned to six groups (n = 6) and administered with normal saline (10 mL/kg, p.o.), N-acetylcysteine (50 mg/kg, i.p.) and ZAE (30, 100, and 300 mg/kg, p.o.) respectively for seven days after which they received paracetamol (PCM, 3000 mg/kg, p.o.). Animals were sacrificed 48 h after paracetamol administration under light anaesthesia and assessed for liver toxicity and oxidative stress. Total flavonoid and phenolic contents of ZAE were 1313.425 µg/mL quercetin equivalence and 268.31 µg/mL gallic acid equivalence respectively. ZAE exhibited marked FRAC as well as DPPH and NO radical scavenging activities with IC50s of 80.41 ± 1.56, 67.56 ± 1.11 and 7.11 ± 1.48 μg/mL respectively. ZAE and N-acetylcysteine significantly (p < 0.05) reduced the paracetamol-mediated elevation of serum total bilirubin, proteins and activity of liver enzymes (AST, ALP, and ALT). Similarly, ZAE increased hepatic glutathione, total thiols and catalase activity of the paracetamol intoxicated rats. Morphological changes associated with the paracetamol hepatotoxicity were also ameliorated by ZAE. Overall, the hepatoprotective effect of ZAE may be related to its antioxidant property.