Background Acetaminophen (APAP) is known as a safe drug for the relief of fever and pain at therapeutic levels. However, APAP toxicity is considered as the most general cause of acute hepatic damage. This research aimed to evaluate the protective effects of Protocatechuic acid (PCA), as an antioxidant, on the APAP-induced liver toxicity in mice. Methods In this regard, we treated male ICR mice with 40, 80, and 160 mg/kg PCA followed by 300 mg/kg APAP 1 h later for 7 days. By passing 24 h from the APAP administration, they were sacrificed, their Liver was dissected, and blood samples were collected for the evaluation of liver function. Results The results show that APAP-overdose (300mg/kg, IP) could lead to acute liver injury in mice, which is characterized by a rise in serum liver function tests (AST, ALT), pathological changes, and a decline in the antioxidant defense system. In addition, hepatic MDA levels, as the end product of lipid peroxidation, have increased, while the antioxidant enzymes such as GPX, SOD, and CAT activities have decreased in mice. In contrast, it was shown that pre-treatment with PCA could decline MDA, ALT, and AST levels and obviously attenuate the liver histological damage and the antioxidant enzymes. Finally, the results show that PCA had protective effects on the APAP-induced liver damage in mice. Conclusions Our studies show that hepatoprotective natural agents can be effective in APAP -liver toxicity.
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