Quinic acid alleviates liver toxicity induced by acetaminophen in mice via anti-oxidative and anti-inflammatory effects.

Acetaminophen (N-acetyl-para-aminophenol: APAP)-induced hepatotoxicity is a common toxicity that is associated with oxidative stress and inflammation. Quinic acid (QA) is a naturally occurring metabolite that exhibits antioxidant and anti-inflammatory properties. In this research, the effect of QA on hepatotoxicity caused by APAP was investigated. The mice were divided into six groups: control, APAP (300 mg/kg, i.p.), QA (100 mg/kg, i.p.), N-acetylcysteine (NAC) (100 mg/kg, i.p.), and treatment groups, which pretreated with QA at two doses of 50 and 100 mg/kg. NAC and QA were injected for 7 days, and APAP was injected on the seventh day. On day 8, mice were euthanized, and serum factors, markers of oxidative stress, tumor necrosis factor-α (TNF-α), and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and cytochrome P450 2E1 (CYP2E1) proteins were measured. The results showed that the APAP-treated group significantly increased the activity of serum enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase). APAP decreased hepatic total thiol content, as well as catalase, superoxide dismutase, and glutathione peroxidase activities, and increased thiobarbituric acid reactive substances and TNF-α levels. In addition, Nrf2 and CYP2E1 protein expression was upregulated in APAP-induced injury. Moreover, histopathological findings confirmed APAP hepatotoxicity. However, QA protected mice against the detrimental effects resulting from an imbalance in the oxidant/antioxidant system. QA ameliorated APAP-induced inflammation and histopathological changes and was able to upregulate the protein expression of Nrf2, while also reversing the increase in protein expression of CYP2E1 in APAP-intoxicated mice. These findings demonstrate the potential of QA in preventing APAP-induced hepatotoxicity, which is comparable to the effects of NAC.