Potential Protective Role of Sitagliptin (Januvia) Against Acetaminophen-Induced Hepatotoxicity in Adult Albino Rats

Acetaminophen (APAP) is a commonly used analgesic-antipyretic drug. Overdose of APAP is significant global clinical problem in humans. Sitagliptin (Sitg) an anti-diabetic drug, has shown protective effects against organs toxicities. This work aimed to evaluate the protective effect of Sitg against APAP-induced hepatotoxicity. Forty male rats were divided into four equal groups. Group-I (control; C-GP; distilled water), Group-II (Sitg-GP; 20-mg/kg), Group-III (APAPGP; 500-mg/kg), and Group-IV (Sitg+APAP-GP; 20-mg/kg+500-mg/kg) pretreated with Sitg followed 2-hour later by APAP. The dosages were given once daily by gavage for 15 days and then blood and liver specimens were collected. Liver biomarkers were assayed in sera and included enzymes (aspartate transaminase=AST; alanine transaminase=ALT; alkaline phosphatase=ALP; gamma-glutamyltransferase=GGT; lactate dehydrogenase=LDH), bilirubin (total bilirubin=TB; direct bilirubin=DB; indirect bilirubin=IB), and proteins (total protein=TP; albumin=ALB; globulin=GLB). Oxidative stress biomarkers were estimated in homogenates and included antioxidants (superoxide dismutase=SOD; catalase=CAT; glutathione peroxidase=GPx; glutathione-S-transferase=GST; glutathione=GSH) and oxidative malondialdehyde (MDA) besides tissue total redox status (total oxidative status=TOS; total antioxidant capacity=TAC; oxidative stress index=OSI; OSI=TOS/TAC). The hepatic lesions were semi-quantitatively scored. In APAP-GP, concentrations of all enzymes and bilirubin, MDA, TOS, and OSI were significantly increased, while levels of all proteins, antioxidants, and TAC were significantly decreased. Histopathological changes showed distorted architecture, increased fibrous deposition, and reduced glycogen contents. Pretreatment with Sitg markedly prevented APAP-induced biochemical and histopathological abnormalities. Sitg possess remarkable hepatoprotective effects against APAPinduced hepatotoxicity and may be useful in treatment of APAP-poisoned patients with diabetes mellitus.