Probiotic Bacillus Spores Protect Against Acetaminophen Induced Acute Liver Injury in Rats

Abstract

Acetaminophen (APAP) is one of the most used analgesics and antipyretic agents in the world. Intoxication with APAP is the main cause of acute liver toxicity in both the US and Europe. Spore-forming probiotic bacteria have the ability to resist harsh gastric and intestinal conditions. The aim of this study was to investigate the possible protective effect of Bacillus (B) species (sp) spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, B. coagulans) against hepatotoxicity induced by APAP in rats. A total of 35 rats were randomly divided into seven groups: group I served as control; group II received silymarin; group III received MegaSporeBioticTM (MSB); group IV received APAP and served as the model of hepatotoxicity; group V received APAP and silymarin; group VI received APAP and MSB; group VII received APAP, silymarin and MSB. The livers for histopathological examination and blood samples were collected on the last day of the experiment. We determined aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total antioxidant capacity (TAC) levels and zonula occludens (ZO-1), tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) expression. APAP overdose increased AST and ALT. It slowly decreased TAC compared to the control group, but pretreatment with silymarin and MSB increased TAC levels. Elevated plasma concentrations were identified for ZO-1 in groups treated with APAP overdose compared with those without APAP or receiving APAP in combination with silymarin, MSB or both. The changes were positively correlated with the levels of other proinflammatory cytokines (TNF-α, IL-1β). In addition, histopathological hepatic injury was improved by preadministration of MSB or silymarin versus the disease model group. Bacillus sp spores had a protective effect on acute hepatic injury induced by APAP. Pretreatment with MSB resulted in a significant reduction in serum AST, ALT, TNF-α, IL-1β, ZO-1, TAC and also hepatocyte necrosis, similar to the well-known hepatoprotective agent—silymarin.

Gut Microbiota and Chemical-Induced Acute Liver Injury

“…Meanwhile, Sharma et al reported that probiotic Enterococcus lactis IITRHR1 and Lactobacillus acidophilus MTCC447 protect against APAP-induced liver injury by modulating the antioxidant capacity of the liver and the expression of key apoptotic/anti-apoptotic proteins (Sharma et al, 2011 ). MegaSporeBioticTM probiotic capsules are composed of a probiotic blend of spores from five Bacillus species that improve the histopathological hepatic injury and decreased the level of proinflammatory cytokines, indicating that Bacillus spa spores have a protective effect on acute hepatic injury induced by APAP (Neag et al, 2020 ). This data is significant for the treatment of ALI and we also need to further explore whether the pretreatment of probiotics could improve the detoxification ability and antioxidant capacity of hepatocytes.…”

The Effects of a Probiotic (Bacillus clausii) in Acute Kidney Injury in a Rat Model of LPS-Induced Endotoxemia

“…B. clausii inhibited secretion of pro-inflammatory cytokines and reactive oxygen species production in rotavirus-infected cells (39). It was demonstrated that pretreatment with probiotic capsules of Bacillus species spores caused a significant decrement in pro-inflammatory cytokines (42). Treatment with B. clausii UBBC07 importantly attenuated oxidative stress by increasing catalase and SOD, and decreasing MDA in acetaminophen-induced uremia in rats (43).…”

Bacillus Licheniformis PF9 Improves Barrier Function and Alleviates Inflammatory Responses Against Enterotoxigenic Escherichia Coli F4 Infection in the Porcine Intestinal Epithelial Cells

“…Many B. licheniformis strains were proved to have the ability to alleviate in ammatory response in vitro and in vivo One study has demonstrated that B. licheniformis strain can signi cantly decrease production of the pro-in ammatory cytokines (IL-8) under the challenge of Salmonella enterica serovar Typhimurium in intestinal epithelial cells [38]. Pretreatment with Bacillus species spores (B. licheniformis, B. indicus, B. subtilis, B. clausii, and B. coagulans) lowered the serum levels of pro-in ammatory cytokines (TNF-α and 1L-1β) against acetaminophen-induced acute liver injury in rats [41]. Similarly, we found that B. licheniformis PF9 treated with pathogenic exposure at the ratios of 1:10, 1:25, 1:50, or 1:100 (ETEC F4 to B. licheniformis PF9) actually attenuated the release of cytokines IL-8 (Fig.…”