Therapeutic Potential of Surface Functionalized Mn3O4 Nanoparticles Against Chronic Liver Diseases in Murine Model

Currently there is a great deal of interest on health benefits of inorganic nanoparticles. Although they have been successfully introduced against several diseases, their direct use in treatment of chronic diseases are sparse in the literature. Chronic liver diseases are the fifth most common cause of death, affecting around 400 million people per year worldwide and have no effective medication. The aim of this study was to evaluate potential hepatoprotective activity of orally administered citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs) against CCl4 induced hepatotoxicity. Our results show that oral treatment of C-Mn3O4 NPs can effectively reduce severe chronic liver damage even fibrosis in CCl4-induced mice model. Further investigations revealed that C-Mn3O4 NPs show increased antioxidant activity upon acid treatment (both in vitro and in vivo i.e., stomach), which is in turn responsible for its hepatoprotective nature. Assessment of various liver function parameters along with histopathology and immunohistochemistry were performed to evaluate pathophysiological condition of the liver. To unravel the mechanisms involved in attenuation of liver injury by NPs, various antioxidant parameters (like superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione etc.) were also examined. An in depth study of the effect of C-Mn3O4 NPs on mitochondria, the cellular mediator of oxidative stress further revealed the molecular mechanism behind its therapeutic efficacy. To best of our knowledge, this is the first study that demonstrates direct oral treatment of an inorganic NPs (i.e., C-Mn3O4 NPs) without any delivery system can efficiently reduce chronic hepatotoxicity and liver fibrosis through its antioxidant activity.