Treatment with milk thistle extract (Silybum marianum), ursodeoxycholic acid, or their combination attenuates cholestatic liver injury in rats: Role of the hepatic stem cells.

BACKGROUND/AIMS: Cholestasis, which results in hepatic cell death, fibrosis, cirrhosis, and eventually liver failure, is associated with oxidative stress. The aim of this study was to evaluate the effects of milk thistle (MT, Silybum marianum) and ursodeoxycholic acid (UDCA) or their combination on the activation of hepatic stem cells and on the severity of cholestasis liver injury in rats. MATERIALS AND METHODS: Under anesthesia, bile ducts of female Sprague Dawley rats were ligated (BDL) or had sham operation. BDL rats were administered saline, UDCA (15 mg/kg/d), MT (600 mg/kg/d), or UDCA+MT by gavage for 10 days. On the 11th day, rats were sacrificed and blood and liver samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) levels, and myeloperoxidase (MPO) activity were measured. Hepatic injury, a-smooth muscle actin expression, and stem cell markers c-kit, c-Myc, Oct3/4, and SSEA-1 were histologically determined. RESULTS: Histological scores, serum ALT, and hepatic MDA levels were higher in BDL group than in the sham rats, while all treatments significantly reduced these levels. The reduction in ALT was significantly greater in UCDA+MT-treated group than in other treatment groups. c-Kit, c-Myc, Oct3/4, and SSEA-1 were increased in saline-treated BDL group with respect to sham-operated control group, and these markers were significantly reduced in all treatment groups. CONCLUSION: In addition to a modulatory effect on the stem cell-induced regenerative response of the liver, UDCA, MT, and their combination demonstrated similar anti-inflammatory and antiproliferative effects on cholestasis-induced hepatic injury.

Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats.

Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTXinduced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.