Thesis (M.Sc.)--Chulalongkorn University, 2011

N-acetyl-p-aminophenol (APAP) or paracetamol overdose is metabolized by cytochrome P450 (CYP 2E1) and a toxic metabolite, mainly N-acetyl-p-benzoquinone imine (NAPQI) is formed, finally, liver injury occurs. Here, we examined the effects of curcumin attenuated hepatitis in mice with APAP overdose. Male mice (25-30 gram) were divided into four groups. Group I (Control); was gavaged with distilled water. Group II (APAP); was gavaged with a single dose of 400 mg/kg APAP dissolve in water. Group III (APAP + CUR 200); was gavaged with a single dose of 400 mg/kg APAP and 200 mg/kg curcumin. Group IV (APAP + CUR 600); was gavaged with a single dose of 400 mg/kg APAP and 600 mg/kg curcumin. The liver was collected for hepatic GSH, hepatic MDA, and liver pathology assays. The serum was collected for hepatic enzymes, IL-12, and IL-18 assays using ELISA technique. Hepatic MDA, hepatic enzymes, serum IL-12, and IL-18 were significantly increased in APAP as compared with control and significantly decreased in APAP + CUR 200 and APAP + CUR 600 as compared with APAP. Hepatic GSH was significantly decreased in APAP as compared with control and significantly increased in APAP + CUR 200 and APAP + CUR 600 as compared with APAP. Liver pathology of APAP showed extensive hemorrhagic hepatic necrosis involving all zones and the improvement of liver pathology revealed in APAP + CUR 200 and APAP + CUR 600. In conclusion, APAP overdose can cause liver injury. The results show that curcumin could attenuate APAP-induced liver injury by decrease oxidative stress, reduce liver inflammation, restoring hepatic GSH, and improve liver pathology. In addition, curcumin at the dose of 600 mg/kg tends to be more potent than 200 mg/kg in preventing the effects of APAP hepatotoxicity. Hence, curcumin might be a novel therapeutic strategy against hepatitis caused by APAP overdose.