Lactic acid bacteria prevent alcohol-induced steatohepatitis in rats by acting on the pathways of alcohol metabolism.

The objective is to study the possible mechanism by which lactic acid bacteria (LAB) prevent alcohol-induced steatohepatitis in rats. A total of 25 Wistar rats were divided into three groups: a LAB-fed group, an alcohol-treated group and a control group. Both the LAB-fed group and the alcohol-treated group received alcohol (10 g kg(-1) per day) orally for up to 5 days (125 h). Before exposure to alcohol, the LAB-fed group were first treated daily with 1.5 ml/100 g of a mixture comprising 4 x 10(10) ml(-1) of Lactobacillus acidophilus and 2.5 x 10(7) ml(-1) of Bifidobacterium longum, while the control group was treated with normal saline only. Biochemical data, alcohol dehydrogenase (ADH) activity and histology of the liver and stomach were evaluated. The ADH activity in the LAB mixture was 3.52 +/- 0.45 mumol mg(-1) protein (10(9) CFU ml(-1)), and was dose-dependent. By 30 min after taking alcohol, serum alcohol concentrations were 514.24 +/- 80.21 microg ml(-1) in the LAB-fed group and 795.15 +/- 203.45 microg ml(-1) in the alcohol-treated group (P < 0.005). Serum alcohol concentrations were reduced by 48% (P < 0.01) in the LAB-fed group, but by only 4% in the alcohol-treated group (P > 0.05) 120 min after oral intake of alcohol. The blood levels of endotoxin, AST and ALT were improved in the LAB-fed group compared to the alcohol-fed group (P < 0.01). All alcohol-treated rats showed moderate to severe steatohepatitis, but the LAB-fed rats showed almost normal histology or very slight lesions only. In conclusion, LAB decreased the alcohol concentration in the blood by increasing the first-pass metabolism in both the stomach and the liver, and effectively protected against alcohol-induced gastric and liver injury. It is interesting to note that the protection was more effective in the liver.

Aflatoxin B1-induced hepatic steatosis: role of carbonyl compounds and active diols on steatogenesis.

Aflatoxin B1 (AFB1) exerts a chronic carcinogenic and an acute toxic effect on animals. Whereas the mechanism for carcinogenicity is known, no mechanism has been proposed for the toxic action. Among the most prominent signs of aflatoxicosis in several species, including birds and mammals, are hypolipidaemia, hypocholesterolaemia, and hypocarotenaemia, associated with severe hepatic steatosis and weight loss. We suggest that these signs of acute imbalance of lipid metabolism can be the result of the chemical modification (blocking) of key lysyl residues on the LDL protein B-100 by the activated AFB1 molecule. Modified LDLs are not recognised by their specific receptors and thus are rejected by peripheral cells. Upon return to the liver, the modified particles bind to the sinusoidal lining cells. Lipid starvation of peripheral tissues takes place while fat accumulates in the liver. This abnormal state is maintained and reinforced by further modification of nascent apoproteins, which in turn become unable to receive a lipid load for as long as aflatoxin continues to be available in the liver.

Cocaine hepatotoxicity during protein undernutrition of retrovirally infected mice.

Effects of cocaine administration on lipid peroxidation and liver damage in immunocompromised mice fed different levels of dietary proteins were investigated. Indices of lipid peroxidation and serum aminotransferases as evidence of free radical attack and liver damage were compared in mice fed a low protein (4%) or regular protein diet (20% protein) for 3 weeks and then infected with murine leukemia virus and given daily intraperitoneal injections of increasing progressive doses of 5-45 mg.kg-1.day-1 of cocaine for 11 weeks. Cocaine administration significantly increased hepatic triglycerides, serum aminotransaminases, conjugated dienes, lipid fluorescence, and malondialdehyde levels. These changes were exacerbated by retroviral infection and also by protein undernutrition. Retroviral infection additively increased indices of cocaine-induced lipid peroxidation and hepatic damage. Significant increases in indices of lipid peroxidation and greater liver injury were also detected in similarly treated mice that received the low protein diet compared with well-nourished mice. These results show that immunocompromised mice fed low levels of dietary protein form significantly increased immunogenic lipid peroxidation adducts during cocaine treatment.

Isoniazid-induced hepatic steatosis in rabbits: an explanation for susceptibility and its antagonism by pyridoxine hydrochloride.

Steatosis was induced in rabbits by subacute administration of isoniazid (INH, 50 mg/kg po). Concomitant treatment with pyridoxine (vitamin B6, 25 mg/kg po) antagonized both development of the hepatic lesions and the elevation of plasma concentrations of lipids. Rabbit acetylating ability was sixfold that of male Wistar rats, a species susceptible to hepatic cell necrosis, whereas hepatic cytochrome P-450 and NADPH-cytochrome c reductase were significantly lower than that observed in control or phenobarbital-induced rats. Examination of the hepatic hydrolysis of the amide bonds of INH and acetylisoniazid (AcINH) indicated that the isonicotinoyl bond of AcINH was the bond most susceptible to amidase hydrolysis in both species; but rabbits possessed the greater amidase activity: 5- to 20-fold greater than control rats and 2- to 7-fold greater than the phenobarbital-induced rats. Consequently, INH-induced hepatic fatty degeneration in rabbits was attributed to increased hepatic exposure to INH-derived primary amine functional groups, and its antagonism by vitamin B6 was attributed to the deactivation of the primary amine by pyridoxal hydrazone formation.

Valproate-induced hepatic steatogenesis in rats.

The administration of high-dose valproic acid (VPA) (750 mg per kg) consistently produced significant microvesicular steatosis in mature Sprague-Dawley rats after 48 hr. Similar changes occurred in animals pretreated with phenobarbital which received a lower dose of VPA (350 mg per kg), but no steatosis was seen in animals treated with the low-dose VPA alone. The steatogenic effect of VPA is most likely mediated by a toxic metabolite. It can also be speculated that phenobarbital, by enhancing the inducing effects of the hepatic mixed-function oxidase system, may lead to increased conversion of VPA to a toxic metabolite. Young and weanling rats appeared to be resistant to the steatogenic effects of VPA. Reproduction of microvesicular steatosis in this experimental; model may permit exploration of factors that enhance or inhibit VPA-induced hepatic injury.

[Hepatic and intestinal toxicity of furazan and furoxan derivatives]. / Tossicita' epatica e intestinale di alcuni derivati furazanici e furossanici.

Histological examination revealed that 4-methylfurazan-3-carboxylic acid hydrazide (I); 3-methylfuroxan-4-carboxylic acid hydrazide (II); 4-methylfurazan-3-carboxylic acid amide(III); 4-methylfuroxan-3-carboxylic acid amide (IV), caused hepatic and intestinal lesion in the mouse. At the higher doses a destruction of the intestinal mucosa and a vasodilatation of the hepatic sinusoid was observed. At lower doses hepatic steatosis was observed.