leptin and Schistosomiasis-mansoni

This study evaluated the possible antifibrotic effect of pentoxifylline on experimentally induced schistosomal hepatic fibrosis and its effect on serum leptin and transforming growth factor-β1 levels as possible antifibrotic mechanisms in correlation with the hepatic fibrosis indices. A total of ninety clean laboratories bred, males Swiss, albino mice were included, of which ten mice served as a control non-infected, non-treated group and sacrificed at one time. Eighty mice, each was subcutaneously infected with 50 Schistosoma mansoni cercariae and classified into groups: GI (infected & non-treated), GII (infected & treated with Mirazid), GIII (infected & treated with Pentoxifylline) and GIV (infected & treated with a combination of Mirazid and Pentoxifylline). Each group was further subdivided into 2 subgroups; subgroup 'a' which started treatment at 6th week post-infection (P.I.) and sacrificed at the end of 9th week P.I and subgroup 'b' which started treatment at 14th week P.I and sacrificed at the end of 17th week P.I. The efficacy of the treatment was assessed by histopathological examination of the liver with measurement of granuloma sizes, estimation of hydroxyproline content in the liver, and assessment of serum levels of leptin and transforming growth factor- β1 (TGF-β1).Mirazid (MZD) caused significant reductions in granuloma sizes and hepatic hydroxyproline content and caused non-significant reductions in serum levels of leptinand transforming growth factor- β1 t 9th & 17t hweeks P.II(GIII. Pentoxifylline (PTX) caused significant reductions in granuloma sizes, hepatic hydroxyproline, and serum levels of leptin and transforming growth factor- β1 t the 9"th& 17kt weeks P.II (GIII. While combined therapy of both MZD & PTX in GIIVcaused more reductions in granuloma sizes, hepatic hydroxyproline, and serum levels of leptin and TGF- β1 t the 9th & 17th weeks P.IIwhen compared to the other groups.

Topics: Animals; Female; Free Radical Scavengers; Leptin; Liver Cirrhosis; Male; Mice; Pentoxifylline; Schistosomiasis mansoni; Transforming Growth Factor beta1

Leptin, a product of the obese (ob) gene is present in activated stellate cells. This study investigated whether leptin is essential for the development of hepatic fibrosis caused by various agents.. Control and ob/ob mice were infected with Schistosoma mansoni or were administered chronic carbon tetrachloride to cause hepatic fibrosis.. Fibrosis developed in both ob/ob and control mice. However, the amount of histologically detectable fibrosis and the increase in liver hydroxyproline content was significantly greater in both models of fibrosis for treated controls than for treated ob/ob mice. Fibrosis was associated with higher secretion of TGFbeta1 from spleen cells of treated control than treated ob/ob mice. Chronic leptin administration in ob/ob mice infected with Schistosoma mansoni resulted in an increase in the amount of fibrosis caused by Schistosoma mansoni, eliminating any significant differences in the amount of fibrosis between infected ob/ob mice and control mice. It also eliminated any significant difference in TGFbeta1 secretion between the infected ob/ob and infected control mice.. This study shows that leptin deficiency decreases but does not eliminate hepatic fibrosis produced by Schistosoma mansoni and carbon tetrachloride administration. The effect of leptin in potentiating fibrogenesis is most likely mediated by TGFbeta1.

Topics: Animals; Carbon Tetrachloride; Cytokines; Drug Administration Schedule; Leptin; Liver; Liver Cirrhosis, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Obesity; Schistosomiasis mansoni; Spleen; Transforming Growth Factor beta; Transforming Growth Factor beta1

Leptin, a product of the obese (ob) gene, was demonstrated previously in activated hepatic collagen-producing stellate cells, but not in quiescent retinol-storing stellate cells. The role of leptin in fibrogenesis is unknown. This study investigated the possible influence of leptin in the pathogenesis of fibrosis by determination of the amount of fibrosis produced by Schistosoma mansoni infection in leptin deficient male ob/ob mice as compared to control mice.. The mice were infected percutaneously with cercaria of Schistosoma mansoni and the amount of liver fibrosis determined 12 weeks after infection. The amount of hepatic collagen deposited was quantified by morphometric analysis of liver sections stained with sirius red and by hydroxyproline content.. The amount of histologically detectable fibrosis was greater in the infected controls than in the infected ob/ob mice. In the infected control mice, but not in the ob/ob mice, the fibrosis surrounding the granuloma was broad and extended beyond the portal tracts into the lobule with the formation of fibrous septa.. This study shows that leptin is a potentiating, but not an essential factor, for the development of hepatic fibrosis, because leptin deficiency reduces but does not prevent the development of hepatic fibrosis.

Topics: Animals; Collagen; Disease Models, Animal; Granuloma; Hydroxyproline; Immunohistochemistry; Leptin; Liver; Liver Cirrhosis, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Schistosoma mansoni; Schistosomiasis mansoni