Hepatoprotective effect of acetaminophen against diethylnitrosamine-induced hepatocellular carcinoma in rats

Abstract Background Liver cancer, particularly hepatocellular carcinoma (HCC), is a major global health concern, showing high recurrence and mortality rates. Chronic inflammation and oxidative stress are key factors in the development of HCC. Previous studies have shown that paracetamol, a common anti-inflammatory drug, prevents HCC by inhibiting the cyclooxygenase pathway and reducing inflammation and oxidative stress. This study aimed to investigate the hepatoprotective effects of acetaminophen against diethylnitrosamine (DEN)–induced HCC in male rats. Methods Male Sprague-Dawley rats (5–6 weeks old, 240–290 g) were divided into control and treatment groups (6 rats each). HCC was intraperitoneally induced with DEN (50 mg/kg body weight) in both groups once a week for 10 weeks. The treatment group also received acetaminophen (200 mg/kg per day) from one week before DEN administration until the 24th week. Liver function biomarkers (aspartate aminotransferase, alanine transaminase [ALT], α-fetoprotein, bilirubin, and albumin) were measured, and liver tissues histopathologically evaluated. Data were analyzed using SPSS software, using Shapiro-Wilk tests for normality and unpaired t tests for comparisons. Results The acetaminophen group showed significant differences in aspartate aminotransferase, ALT, and bilirubin levels over time, which were higher than those of the control group ( p < 0.05). Rats in the control group exhibited substantial liver damage and early death, whereas those in the treatment group showed improved survival and liver function. Histopathological analysis revealed fewer necrotic and precancerous changes in the treatment group. Albumin levels were significantly associated with cirrhosis manifestation ( p = 0.005), and ALT and bilirubin levels correlated with precancerous conditions ( p < 0.05). Conclusions Acetaminophen at 200 mg/kg body weight protected rat hepatocytes against DEN-induced liver damage and potential carcinogenesis. Our findings could serve as a basis for developing future research approaches in patients with HCC undergoing liver resection that are aimed at preventing recurrence and reducing inflammation.