Effect of metformin on histopathological and immunohistochemical changes induced by high fructose intake in liver and brain of rats

Fructose is widely used as a food ingredient and has the potential to increase oxidative stress and related complications. The present study was designed to evaluate the role of metformin on histopathological and immunohistochemical changes in liver and brain of rat induced by high fructose intake. Forty male albino rats were divided into 4 groups. Groups I and II served as controls. Group III received 10 % drinking fructose solution for eight weeks. Group IV was received 10 % drinking fructose solution for eight weeks and treated with metformin (320 mg/kg/day) during the last 4 weeks of the experimental period. Rats were sacrificed after 8 weeks; liver and brain were excised and fixed in 10% neutral buffered formalin. Histopathological results: Fructose drinking manifested changes in liver and brain cerebral cortex. Liver changes were manifested as inflammation, apoptosis, dilated sinusoids, fibrosis, macrosteatosis, ballooned hepatocytes and marked collagen deposition, while brain changes were degenerating neurons, steatosis, karyorrhexis, and pyknotic nuclei in nuropil and lightly stained Nissl substance with cresyl violet. Metformin treatment eliminated histopathological changes in addition to decreased collagen deposition in liver and improved Nissl substance staining in brain. Immunohistochemical results showed increased immunostaining positivity of caspase-3 and inducible nitric oxide synthase ( iNOS) in liver and brain in fructose group . Reduced immunoreactivity of caspase-3 and iNOS in fructose plus metformin group either in liver or brain sections. In conclusion, the results suggest that the hepatoprotective and neuroprotective role of metformin on histopathological and and immunohistochemical changes induced by fructose could be attributed to its ability to reduce oxidative stress.