Histological and immunohistochmeical studies on the postulated protective and therapeutic roles of pentoxifylline on thioacetamide induced hepatic injury in adult male albino rats

ABSTRACT

Thioacetamide induces liver injury, with histological alterations similar to those observed in human cirrhosis, through releasing of tumour necrotising factor-alpha. Pentoxifylline is an anti-tumour necrotising factor-alpha which might decrease the hepatic injury. This study investigated the histological and imniunohistochemical basis for the postulated beneficial role of pentoxifylline on the thioacetamide induced liver injury. Fifty adult male albino rats were divided into 5 equal groups; group I [Control 1] Rats were intraperitoneally injected once daily with distilled water for 8 days; group II [Control 2] Rats were intraperitoneally injected with pentoxifylline [200 mg/kg body wt] once daily for 8 days; group III [Liver injury induced group] Rats were intraperitoneally injected with thioacetamide [50 mg/kg] once daily for 8 days; group IV [Preventive group] rats were concomitantly intraperitoncally injected with pentoxifylline and thioacetamide in doses and duration similar to groups II and III, respectively; group V [Therapeutic group] Rats were injected with thioacetamide for 8 days as in group III and then injected with pentoxifylline from day 9 to day 16 in similar doses as in group II. Blood samples were collected for estimation of liver enzymes. Liver was removed and used for light and transmission electron microscopical studies. For light microscopic study, the paraffin sections were stained with Haematoxylin and Eosin, Periodic Acid Schiff, Azan stain and immunohistochemically for tissue tumour necrotising factor-alpha. Using image analyzer, quantitative measurements and analysis of the optical densities for the Periodic Acid Schiff, Azan and tumour necrotising factor-alpha positive reactions were done. One-way ANOVA followed by Dunnett's test and Pearson's correlation coefficient [r] were used. Thioacetamide [Group III] led to elevated liver enzymes. Light microscopical study revealed degeneration and necrosis of hepatocytes, reduced glycogen, increased collagen and increased expression of tumour necrotising factor-alpha in the liver tissue. Electron microscopic study revealed degeneration of the cellular organelles. These changes were attenuated by using the pentoxifylline in preventive and to some extent in therapeutic groups. Thioacetamide induced hepatic injury can be prevented and treated by using pentoxifylline