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. 2009 Mar;43(2):163-72.
doi: 10.1016/j.alcohol.2008.12.009.

V体育官网 - Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis

Christopher B Forsyth  1 , Ashkan Farhadi, Shriram M Jakate, Yueming Tang, Maliha Shaikh, Ali Keshavarzian
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"VSports注册入口" Lactobacillus GG treatment ameliorates alcohol-induced intestinal oxidative stress, gut leakiness, and liver injury in a rat model of alcoholic steatohepatitis

Christopher B Forsyth et al. Alcohol. 2009 Mar.

Abstract (VSports手机版)

Because only 30% of alcoholics develop alcoholic liver disease (ALD), a factor other than heavy alcohol consumption must be involved in the development of alcohol-induced liver injury. Animal and human studies suggest that bacterial products, such as endotoxins, are the second key co-factors, and oxidant-mediated gut leakiness is one of the sources of endotoxemia. Probiotics have been used to prevent and treat diseases associated with gut-derived bacterial products and disorders associated with gut leakiness. Indeed, "probiotic"Lactobacillus rhamnosus has been successfully used to treat alcohol-induced liver injury in rats. However, the mechanism of action involved in the potential beneficial effects of L. rhamnosus in alcohol liver injury is not known VSports手机版. We hypothesized that probiotics could preserve normal barrier function in an animal model of ALD by preventing alcohol-induced oxidative stress and thus prevent the development of hyperpermeability and subsequent alcoholic steatohepatitis (ASH). Male Sprague-Dawley rats were gavaged with alcohol twice daily (8 gm/kg) for 10 weeks. In addition, alcoholic rats were also treated with once daily gavage of either 2. 5 x 10(7) live L. rhamnosus Gorbach-Goldin (LGG) or vehicle (V). Intestinal permeability (baseline and at 10 weeks) was determined using a sugar bolus and GC analysis of urinary sugars. Intestinal and liver tissues were analyzed for markers of oxidative stress and inflammation. In addition, livers were assessed histologically for severity of ASH and total fat (steatosis). Alcohol+LGG (ALC+LGG)-fed rats had significantly (P< or =. 05) less severe ASH than ALC+V-fed rats. L. rhamnosus Gorbach-Goldin also reduced alcohol-induced gut leakiness and significantly blunted alcohol-induced oxidative stress and inflammation in both intestine and the liver. L. rhamnosus Gorbach-Goldin probiotic gavage significantly ameliorated ASH in rats. This improvement was associated with reduced markers of intestinal and liver oxidative stress and inflammation and preserved gut barrier function. Our study provides a scientific rationale to test probiotics for treatment and/or prevention of alcoholic liver disease in man. .

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Figures

Figure 1
Figure 1. The effect of Lactobacillus GG on the severity of alcoholic steatohepatitis assessed by the total liver histology and liver necroinflammation scores
After 10 weeks liver tissues from rats in the four gavage treatment groups were processed, stained (H&E) and assessed histologicalIy and total histology scores and necroinflammation scores were calculated as described in Methods. Fig.1a shows representative liver histology slides from each of the 4 treatment groups (400×, bar = 20μm). Large arrow denotes area of focal necrosis and inflammatory cell infiltration, small arrow is additional inflammatory cell infiltration. Fig. 1b histogram summarizes the necroinflammatory scores for the four groups. Treatment groups were: Control: isocaloric dextrose; Alcohol: alcohol + vehicle: 8g/kg/day ethanol; Alcohol + LGG (Alc+LGG): ethanol 8g/kg/day + Lactobacillus GG 2.5 × 107/day; Control + LGG (Con+LGG): isocaloric dextrose + Lactobacillus GG 2.5 × 107/day. Data are histology and necroinflammation score means ± standard error of the mean (S.E.) expressed as a percent of the alcohol alone treated group (% ALC). * denotes significance (ANOVA) of p ≤ .05 for alcohol group versus alcohol + LGG group in all figures.
Figure 1
Figure 1. The effect of Lactobacillus GG on the severity of alcoholic steatohepatitis assessed by the total liver histology and liver necroinflammation scores
After 10 weeks liver tissues from rats in the four gavage treatment groups were processed, stained (H&E) and assessed histologicalIy and total histology scores and necroinflammation scores were calculated as described in Methods. Fig.1a shows representative liver histology slides from each of the 4 treatment groups (400×, bar = 20μm). Large arrow denotes area of focal necrosis and inflammatory cell infiltration, small arrow is additional inflammatory cell infiltration. Fig. 1b histogram summarizes the necroinflammatory scores for the four groups. Treatment groups were: Control: isocaloric dextrose; Alcohol: alcohol + vehicle: 8g/kg/day ethanol; Alcohol + LGG (Alc+LGG): ethanol 8g/kg/day + Lactobacillus GG 2.5 × 107/day; Control + LGG (Con+LGG): isocaloric dextrose + Lactobacillus GG 2.5 × 107/day. Data are histology and necroinflammation score means ± standard error of the mean (S.E.) expressed as a percent of the alcohol alone treated group (% ALC). * denotes significance (ANOVA) of p ≤ .05 for alcohol group versus alcohol + LGG group in all figures.
Figure 2
Figure 2. The effect of Lactobacillus GG on the severity of alcoholic steatohepatitis assessed by liver fat content and liver MPO levels
After 10 weeks liver tissue from the treatment groups described in Fig. 1 was assessed for myeloperoxidase (MPO) (Fig. 2a.) and total fat (mg fat/gram liver) (Fig. 2b) as described in Methods. Data are for means (as % alcohol group) ± S.E.
Figure 2
Figure 2. The effect of Lactobacillus GG on the severity of alcoholic steatohepatitis assessed by liver fat content and liver MPO levels
After 10 weeks liver tissue from the treatment groups described in Fig. 1 was assessed for myeloperoxidase (MPO) (Fig. 2a.) and total fat (mg fat/gram liver) (Fig. 2b) as described in Methods. Data are for means (as % alcohol group) ± S.E.
Figure 3
Figure 3. The effect of Lactobacillus GG on the severity of hepatic oxidative stress assessed by liver carbonyl and nitrotyrosine levels
Liver tissue from the four treatment groups was assessed after 10 weeks for markers of oxidative stress namely liver carbonyl (Fig. 3a) and liver nitrotyrosine (Fig. 3b) by slot blot and densitometry as described in Methods. Data are means of relative density (as % alcohol group) ± S.E.
Figure 3
Figure 3. The effect of Lactobacillus GG on the severity of hepatic oxidative stress assessed by liver carbonyl and nitrotyrosine levels
Liver tissue from the four treatment groups was assessed after 10 weeks for markers of oxidative stress namely liver carbonyl (Fig. 3a) and liver nitrotyrosine (Fig. 3b) by slot blot and densitometry as described in Methods. Data are means of relative density (as % alcohol group) ± S.E.
Figure 4
Figure 4. Effect of Lactobacillus GG on alcohol-induced intestinal permeability
Whole intestinal permeability to Sucralose was assessed at 10 weeks in the four treatment groups by analysis of 5h urine samples with gas chromatography (Methods). Data are means of percent oral Sucralose dose recovered in urine (as % alcohol group) ± S.E.
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