Hepatoprotective effect of pentoxifylline against D-galactosamine-induced hepatotoxicity in rats.

The present study was conducted to investigate effect of pentoxifylline (PTX) on acute liver injury caused by galactosamine (D-Gal) in rats and the underlying mechanism involved in this setting. Moreover, we attempted to compare its effect to the well-established hepatoprotective agent, silymarin (SYM). The rats were randomly assigned 5 groups, control, PTX-treated (100 mg/kg, 3 weeks), SYM-treated (100 mg/kg, 3 weeks) and their combination. Hepatic injury was induced by intraperitoneal single dose injection of D-Gal (800 mg/kg). Hepatic functions parameters, including serum albumin and alkaline phosphatase (ALP) levels were determined. Antioxidants enzyme activities such as superoxide dismutase (SOD), catalase (CAT) as well as lipid peroxides and hepatic total nitrites were measured. Besides, histopathological examination was also performed using portions of liver tissues. Results showed that the liver injury induced by D-Gal was improved in the three pretreated groups to variable extents. Pretreatment with PTX prevented D-Gal-induced reduction of antioxidant enzyme activities, SOD and CAT, and attenuated the elevated malonaldahyde (MDA) level in hepatic tissue as marker of lipid peroxidation. In addition, pretreatment with PTX resulted in an increase in hepatic triglycerides, normalization of nitric oxide level, and lowering serum ALP activity as well as inhibited the decreased serum albumin level caused by D-Gal. These biochemical changes were reflected on attenuation the structural alterations of the liver integrity. Collectively, our data suggest that PTX exhibits a potential hepatoprotective effect against D-Gal-induced hepatotoxicity and this effect might be attributed to its antioxidant properties.

Lactobacillus casei: influence on the innate immune response and haemostatic alterations in a liver-injury model.

UNLABELLED: Lactobacilllus casei CRL 431 has the ability to modulate the local and systemic immune responses, which are significantly involved in liver injury caused by hepatotoxins. This work was conducted to determine whether L. casei has a preventive effect on the hepatic damage undergone during an acute liver injury (ALI). METHODS: ALI was induced by an intraperitoneal injection of d-galactosamine (D-Gal). Different groups of mice received 1x 109 L. casei cells/day/mouse for 2 days before D-Gal injection. Blood and liver samples were obtained 0, 6, 12, and 24 h after D-Gal administration. RESULTS: D-Gal induced increases in serum aminotransferases, reduced the number of blood leukocytes, enhanced neutrophil myeloperoxidase activity, increased dead cells, and altered prothrombin time and plasma fibrinogen levels. The preventive treatment with L. casei for 2 days modulated the innate immune response. This effect was shown by the earlier normalization of white blood cell counts, myeloperoxidase activity and aminotransferases levels. However, the haemostatic parameters were only partially recovered. The favourable effects obtained could be due to the capacity of L. casei to moderate the inflammatory response at the site of the injury with less damage to liver tissue.

1,8-cineole protects against liver failure in an in-vivo murine model of endotoxemic shock.

The effects of 1,8-cineole on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg(-1), i.p.) and LPS (5 microg kg(-1), i.p.) greatly elevated serum concentrations of tumour necrosis factor-alpha (TNF-alpha), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg(-1), p.o.) and dexamethasone (1 mg kg(-1), s.c.), 60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-alpha and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPS-induced liver injury through the inhibition of TNF-alpha production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies.