Metformin beyond an anti-diabetic agent: A comprehensive and mechanistic review on its effects against natural and chemical toxins

In addition to the anti-diabetic effect of metformin, a growing number of studies have shown that metformin has some exciting properties, such as anti-oxidative capabilities, anticancer, genomic stability, anti-inflammation, and anti-fibrosis, which have potent, that can treat other disorders other than diabetes mellitus. We aimed to describe and review the protective and antidotal efficacy of metformin against biologicals, chemicals, natural, medications, pesticides, and radiation-induced toxicities. A comprehensive search has been performed from Scopus, Web of Science, PubMed, and Google Scholar databases from inception to March 8, 2023. All in vitro, in vivo, and clinical studies were considered. Many studies suggest that metformin affects diseases other than diabetes. It is a radioprotective and chemoprotective drug that also affects viral and bacterial diseases. It can be used against inflammation-related and apoptosis-related abnormalities and against toxins to lower their effects. Besides lowering blood sugar, metformin can attenuate the effects of toxins on body weight, inflammation, apoptosis, necrosis, caspase-3 activation, cell viability and survival rate, reactive oxygen species (ROS), NF-κB, TNF-α, many interleukins, lipid profile, and many enzymes activity such as catalase and superoxide dismutase. It also can reduce the histopathological damages induced by many toxins on the kidneys, liver, and colon. However, clinical trials and human studies are needed before using metformin as a therapeutic agent against other diseases.