Abstract
Acetaminophen (APAP) overdose is among the main causes of drug-induced hepatotoxicity which is predominantly mediated by oxidative stress, inflammatory responses and immune deregulation. The antioxidant and immunomodulatory effects of probiotics and especially Lactobacillus rhamnosus GG (LGG) are well known but their protective and therapeutic effects against the APAP induced liver injury still need to be well defined. In this research, male Swiss Balb/c mice aged adults were randomly selected into five experimental groups which included vehicle control, probiotic control, probiotic pretreatment followed by APAP, APAP-only treatment, and APAP followed by probiotic treatment. LGG was used orally, whereas hepatotoxicity was caused using APAP. Four weeks later, the markers of oxidative stress (glutathione peroxidase-1 [GPx-1] and malondialdehyde [MDA]) and immunological (tumor necrosis factor-alpha [TNF-alpha]) and hepatic histopathological parameters were assessed with the help of standard biochemical, immunological, and histological. The APAP use caused pronounced oxidative stress and inflammatory reactions with a significant rise in the level of GPx-1, MDA and TNF-alpha and significant decrease in the concentration of IgG. Conversely, LGG supplementation had a significant suppressive effect on lipid peroxidation, an activity of antioxidant enzymes, and an increase in immune parameters to near-controlling levels. Histopathology explained that the APAP-treated mice have shown serious hepatic damages, and the probiotic-treated groups presented with slight histological changes, which were primarily characterized by Kupffer cell proliferation and mild mononuclear cell invasion in four weeks. Finally, LGG supplementation is useful in alleviating the APAP-induced hepatotoxicity by antioxidant, anti-inflammatory, and immunomodulatory effects. This information points to the hepatoprotective effect of Lactobacillus rhamnosus GG and justifies its potential application as a prophylactic or therapeutic approach to acetaminophen-induced hepatic injury.

Key words: Acetaminophen, Probiotics, Hepatotoxicity, Oxidative stress, Lactobacillus rhamnosus GG