Background: Acetaminophen (APAP) overdose, common during pandemics like COVID-19, causes liver injury through oxidative stress. Ginger, known for its antioxidant properties, is suggested as a potential natural remedy. Objective: This study aimed to evaluate the therapeutic and prophylactic efficacy of ethanol ginger extract (GE) and ginger suspension (GS) on APAP-induced hepatotoxicity and dyslipidemia in rats. Methods: Rats were assigned to ten groups: a control group, dimethyl sulfoxide group, and groups receiving either GE or GS (150 mg/kg) for two weeks. A group given a single high dose of APAP (2500 mg/kg), groups pre-treated with GE or GS before a single dose of APAP, a group receiving three repeated doses of APAP (500 mg/kg), and groups co-administrated GE or GS along with APAP over two weeks. Results: APAP administration at the two regimens significantly impaired liver function, antioxidant defenses, and lipid metabolism. These disruptions included reduced levels of antioxidant markers such as reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), and glucose-6-phosphate dehydrogenase (G6PDH). Lipid metabolism alterations were evident from increased triacylglycerols (TAGs), total cholesterol (T-chol), low-density lipoprotein cholesterol (LDL-chol), alongside decreased high-density lipoprotein cholesterol (HDL-chol). The high dose of APAP resulted in severe damage, indicated by elevated malondialdehyde (MDA), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and altered protein fractions. Both GE and GS treatments significantly alleviated these APAP-induced changes, particularly in MDA, ALT, GPx, and LDL-chol levels. GE demonstrated superior protective effects compared to GS, particularly in restoring levels of GSH, ALP, CAT, SOD, GST, GR, G6PDH, HDL-chol, albumin and alpha-1 globulins. In contrast, GS showed slightly greater effects on reducing TAGs and T-chol levels. Conclusions: Ginger extracts offer significant protection against APAP-induced liver damage and dyslipidemia, with GE providing more pronounced therapeutic effects.
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