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. 2020 Feb 27;12(3):632.
doi: 10.3390/nu12030632.

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

Maria Adriana Neag  1 , Adrian Catinean  2 , Dana Maria Muntean  3 , Maria Raluca Pop  1 , Corina Ioana Bocsan  1 , Emil Claudiu Botan  4 , Anca Dana Buzoianu  1
Affiliations

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

Maria Adriana Neag et al. Nutrients. .

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.

Keywords: Bacillus spores; acetaminophen; acute hepatotoxicity; inflammation; tight junction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Changes in AST (dotted) and ALT (lined) levels. Rats were treated with 1% CMC, APAP, MSB or SIL either alone or in various combinations (as indicated). Periorbital blood was collected on Day 13, and the serum was tested for AST and ALT levels. * Significant difference (p < 0.05) between groups; data were analyzed using one-way ANOVA. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™; SIL, silymarin.
Figure 2
Figure 2
Rats were treated with 1% CMC, SIL, MSB, APAP, APAP + SIL, APAP + MSB or APAP + SIL + MSB. Periorbital blood was collected on Day 13, and the serum was tested for TNF-α (A) and IL-1β (B) levels. * Significant difference (p < 0.05) between groups; data were analyzed using one-way ANOVA. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; IL-1β, interleukin 1β; MSB, MegaSporeBiotic™; SIL, silymarin; TNF-α, tumoral necrosis factor α.
Figure 3
Figure 3
Changes in TAC levels. Rats were treated with 1% CMC, APAP, MSB or SIL either alone or in various combinations (as indicated). Periorbital blood was collected on Day 13, and the serum was tested for TAC levels. * Significant difference (p < 0.05) between groups; data were analyzed using one-way ANOVA. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™; TAC, total antioxidant capacity; TRL, Trolox; SIL, silymarin.
Figure 4
Figure 4
Rats were treated with 1% CMC, APAP, MSB or silymarin either alone or in various combinations (as indicated). Livers were collected after 13 days, formalin-fixed, and embedded in paraffin. Tissue sections were then stained with hematoxylin and eosin and examined for signs of inflammation and liver damage. Control/CMC (group I), (A) APAP (group IV), (B) APAP + silymarin (group V), (C) APAP + MSB (group VI), (D) APAP + silymarin + MSB (group VII), (E) groups of rats. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™.
Figure 4
Figure 4
Rats were treated with 1% CMC, APAP, MSB or silymarin either alone or in various combinations (as indicated). Livers were collected after 13 days, formalin-fixed, and embedded in paraffin. Tissue sections were then stained with hematoxylin and eosin and examined for signs of inflammation and liver damage. Control/CMC (group I), (A) APAP (group IV), (B) APAP + silymarin (group V), (C) APAP + MSB (group VI), (D) APAP + silymarin + MSB (group VII), (E) groups of rats. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™.
Figure 4
Figure 4
Rats were treated with 1% CMC, APAP, MSB or silymarin either alone or in various combinations (as indicated). Livers were collected after 13 days, formalin-fixed, and embedded in paraffin. Tissue sections were then stained with hematoxylin and eosin and examined for signs of inflammation and liver damage. Control/CMC (group I), (A) APAP (group IV), (B) APAP + silymarin (group V), (C) APAP + MSB (group VI), (D) APAP + silymarin + MSB (group VII), (E) groups of rats. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™.
Figure 4
Figure 4
Rats were treated with 1% CMC, APAP, MSB or silymarin either alone or in various combinations (as indicated). Livers were collected after 13 days, formalin-fixed, and embedded in paraffin. Tissue sections were then stained with hematoxylin and eosin and examined for signs of inflammation and liver damage. Control/CMC (group I), (A) APAP (group IV), (B) APAP + silymarin (group V), (C) APAP + MSB (group VI), (D) APAP + silymarin + MSB (group VII), (E) groups of rats. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™.
Figure 4
Figure 4
Rats were treated with 1% CMC, APAP, MSB or silymarin either alone or in various combinations (as indicated). Livers were collected after 13 days, formalin-fixed, and embedded in paraffin. Tissue sections were then stained with hematoxylin and eosin and examined for signs of inflammation and liver damage. Control/CMC (group I), (A) APAP (group IV), (B) APAP + silymarin (group V), (C) APAP + MSB (group VI), (D) APAP + silymarin + MSB (group VII), (E) groups of rats. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™.
Figure 5
Figure 5
Changes in tight junction protein (ZO-1) levels. Rats were treated with 1% CMC, SIL, MSB, APAP, APAP + SIL, APAP + MSB or APAP + SIL + MSB. Periorbital blood was collected on Day 13 and the serum was tested for ZO-1 levels. * Significant difference (p < 0.05) between groups; data were analyzed using one-way ANOVA. Abbreviations: APAP, N-acetyl-p-aminophenol or paracetamol (acetaminophen); CMC, carboxymethylcellulose; MSB, MegaSporeBiotic™; SIL, silymarin; ZO-1, zonula occludens.
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