Protective efficacy of dapagliflozin against schistosomiasis mansoni-induced liver pathology: an in vivo study

Abstract

Abstract Schistosomiasis is a neglected tropical disease associated with significant morbidity and mortality. Treatment with praziquantel; the sole current medication for human schistosomiasis, is associated with incomplete resolution of Schistosoma mansoni -induced liver pathology. Therefore, there is a crucial need to introduce adjuvant agents that can mitigate the pathological events. This study aims to assess the hepatoprotective effects of the oral anti-diabetic drug dapagliflozin, alone and in combination with praziquantel. In the present research, combined dapagliflozin and praziquantel therapy caused significant decrease in adult worm burden and hepatic egg load, significant increase in the percent of mature and dead eggs and significant reduction in the percent of immature eggs in the small intestine, significant increase in hepatic levels of reduced glutathione and nitric oxide, significant attenuation of histopathological changes, and significant reduction in granuloma count and diameter. Additionally, immunohistochemical study of cleaved-caspase 3 revealed increased expression, compared to the untreated group. Our findings provide insight into dapagliflozin use as an advantageous adjuvant to praziquantel in alleviating schistosomal liver pathology. Future studies are needed to explore other pathways responsible for the hepatoprotective effects of dapagliflozin against Schistosoma-mansoni -induced liver fibrosis.