The hepatoprotective effect of the probiotic Clostridium butyricum against carbon tetrachloride-induced acute liver damage in mice

Abstract

Previous studies have revealed that the probiotic Clostridium butyricum (C. butyricum) can attenuate cirrhosis in chronic non-alcoholic liver disease. However, the effects of C. butyricum on acute liver injury (ALI) remain unclear. Therefore, the present study aims to examine the hepatoprotective effects and the underlying mechanisms employed by C. butyricum in a carbon tetrachloride (CCl)-induced ALI murine model. Here, we evaluated the survival rate and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), anti-oxidants, cytokines and the gut microbiota to elucidate the potential mechanisms by which C. butyricum is hepatoprotective. Our results show that five days of prophylactic C. butyricum treatment significantly reduced mortality by 40% and decreased the CCl-induced levels of ALT and AST in the serum of these mice. Additionally, prophylactic treatment with C. butyricum increased the activity of both superoxide dismutase (SOD) and catalase (CAT), and substantially reduced malondialdehyde (MDA) levels, which were deteriorated in the untreated ALI mice compared to normal control mice. Furthermore, C. butyricum up-regulated the nuclear factor (erythroid-derived 2)-like 2 (NRF2) content. CCl-induced mice also exhibited considerable increases of phosphorylation of nuclear factor-kappa B (NF-κB) p65 and pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). However, the inflammatory responses of the liver induced by CCl were significantly alleviated by C. butyricum pretreatment. Additionally, we found that interleukin-10 (IL-10), an anti-inflammatory mediator, was increased in the C. butyricum-pretreated group. Microbiota analysis in these mice revealed crosstalk between the gut microbial metabolites and ALI. The intestinal flora was changed by CCl administration and was shifted by the probiotic C. butyricum toward more beneficial bacteria, particularly the Clostridia orders, which are the known producers of the anti-inflammatory and anti-oxidative metabolite butyrate. In conclusion, we found that the intestinal flora changes after the intraperitoneal injection of CCl. We also offer novel insights into the mechanism by which probiotic C. butyricum pretreatment alleviates the CCl-induced inflammation and oxidative stress of the liver via the modulation of NRF2, NF-κB p65, IL-10 and the intestinal microbiota in mice.

Combination of metformin and luteolin synergistically protects carbon tetrachloride‐induced hepatotoxicity: Mechanism involves antioxidant, anti‐inflammatory, antiapoptotic, and Nrf2/HO‐1 signaling pathway

“…57,58 This binding causes the downstream activation of HO-1. 59 The present study stated enhanced nuclear accumulation of Nrf2 by triptolide in the case of reperfused hepatic tissue. In addition to this, HO-1 activity was upregulated by treatment with Met and Lut.…”

“…Nrf2 then translocates to the nucleus and binds to the ARE . This binding causes the downstream activation of HO‐1 . The present study stated enhanced nuclear accumulation of Nrf2 by triptolide in the case of reperfused hepatic tissue.…”

Protective Effects of Propolis and Probiotic Lactobacillus acidophilus against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

“…Previous studies have shown similar results on hepatoprotective of propolis, 24 but only a few studies have attempted to determine the protective role of probiotics on CCl4-induced liver toxicity. 25 As shown in Figure 2, CCl4 caused an increase of serum cholesterol and triglycerides levels (p < 0.01), which was reversed by a pretreatment with PRS or L. acidophilus. This is in agreement with earlier study pointing out that PRS modulates cholesterol levels and protects the cardiovascular system through an anti-inflammatory action.…”

Hepatoprotective Effects of Lactobacillus on Carbon Tetrachloride-Induced Acute Liver Injury in Mice

“…These two kinds of free radicals can eventually lead to hepatic lesions by attacking polyunsaturated fatty acids in biofilm phospholipids and trigger lipid peroxidation reactions [11]. Based on CCl 4 -induced hepatic injury animal models, the study of the hepatoprotective effect of microorganisms has made some progress [12,13,14]. …”