Acetaminophen (APAP), an antipyretic/ analgesic drug, is reported to cause toxicity on overdose. Dietary supplements are currently being explored to decrease toxicity. In the present study, the protective effect of probiotic Enterococcus lactis IITRHR1 was evaluated at different doses (107, 108, and 109 colony-forming units) against APAP-induced liver damage. Male Wistar rats were administered APAP (1 g/kg of body weight orally) for 14 d, and hepatotoxicity was assessed by marker enzymes in serum and observation of histopathologic changes. Rats were pretreated with probiotic E. lactis IITRHR1 for 7 d and modulation of antioxidant enzymes (super-oxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase), redox ratio, and ferric reducing antioxidant power was assessed. Oxidative damage by APAP to membrane lipids, proteins, and DNA was also observed. Involvement of Bax, Bcl2, cytochrome c (pro-anti-apoptotic proteins), caspases, and their modulation was assessed by immunoblot analysis and reverse transcriptase polymerase chain reaction. The E. lactis IITRHR1 pretreatment lowered the level of biomarkers of hepatotoxicity in serum. A significant increase was observed in the level of antioxidant enzymes and redox ratio and decreased oxidative damage to membrane lipids and proteins. Probiotic E. lactis IITRHR1 also modulated key apoptotic/anti-apoptotic proteins such as cytochrome-c, Bcl2, Bax, expression of caspases, and resultant DNA damage. Probiotic strain E. lactis IITRHR1 was found to have antioxidant capacity and afforded protection against APAP-induced hepatotoxicity by modulating antioxidant status, pro-antiapoptotic proteins, caspases, and DNA damage.

Sharma et al.; Nutrition; 2012; 28; 173-181.

 

Expression levels of caspase-3/-9. Relative intensity was normalized with GAPDH (used as an internal control). The sequence of samples in blot is (1) control; (2) APAP treatment; (3) 107 CFU of Enterococcus lactis IITRHR1 pretreated APAP; (4-6) Different conc.of E. lactis IITRHR1 + APAP; (7) vit C +APAP. APAP: acetaminophen; CFU:colony-forming units; Con: control; GAPDH:glyceraldehyde 3-phosphate dehydrogenase; vit C: vitamin C.