| Summary: | Gastric ulcer and hepatotoxicity due to irrational drug overuse are two of the most serious conditions associated with inflammation and oxidative stress that affect the digestive system. This study aimed to experimentally evaluate the hepatoprotective/gastroprotective effects of aqueous and butanol citrus peel extracts and hesperidin in rat models of ulcer and hepatotoxicity. Acute toxicity study was performed for determining the safe dose of citrus extracts to analyze efficacy. In the experiments on hepatoprotective and gastroprotective effects, rats were classified into nine groups in each experiment: (1) negative control, (2) positive control hepatotoxic model with paracetamol (640 mg/kg)/gastric ulcer model:ethanol 70% (1 ml), (3)reference hepatoprotective:silymarin (25 mg/kg)/gastroprotective:ranitidine (50 mg/kg), and (4–9) groups treated for 2 weeks before induction of each disease with either citrus aqueous or butanol extracts or hesperidin (125–250 mg/kg). Drugs, ethanol, or tested compounds were administered orally. The levels of biochemical parameters, such as AST, ALT, NO, MDA, CRP, and ILβ6, were significantly reduced, but CAT level was increased. Postmortem examination of liver and stomach tissues of treated animals revealed marked improvement compared with positive control animals. Hesperidin exerted the best hepatoprotective, antioxidant, anti-inflammatory, and gastroprotective effects, followed by butanol and then aqueous citrus peel extracts.
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