Phyto-chlorophyllin Prevents Food Additive Induced Genotoxicity and Mitochondrial Dysfunction via Cytochrome c Mediated Pathway in Mice Model

Objectives: The issue of food-additive-toxicity causing several health hazards needs to be therapeutically managed with an immediate effect. Alloxan, a food additive, is used for whitening and shining flour. It is capable of inducing genotoxicity, diabetes, and associated mitochondrial dysfunction. Therefore, to explore a non-toxic, phyto-based compound that can delay the onset of diabetes and prevent the multitude of damage associated, Chlorophyllin (CHL) was selected for our study, having been reported to exhibit anti-cancer, anti-diabetes, and antiinflammatory responses. Therefore, the objective of the present study is to evaluate the protective role of CHL in controlling genotoxicity, glucose imbalance, and associated cytochrome c mediated mitochondrial signaling dysfunction against food-additive-induced genotoxicity, diabetic state, and its complexities in mice model in vivo. Methods: Mice were pre-treated with CHL through oral gavage before they were exposed to alloxan. Diabetic markers, anti-oxidant enzyme profile, chromosomal study, mitochondrial functioning factors, and expression of proteins were checked against food-additive injected mice. Results: The results revealed that CHL pre-treatment could delay the onset of diabetes, restrict alloxan-induced elevation of blood glucose, reduce DNA-damage and chromosomal aberration, optimize enzymatic profile (glucokinase, pyruvate, insulin), and modulates protein expression (insulin, IRS1, IRS2, GLUT2). Further, CHL-pre-treatment could stabilize mitochondrial-membrane-potential, intracellular calcium ion, ATP/ADP ratio, ATPase activity, thereby maintaining optimum functioning of cytochrome-c, bcl2, and caspase3 mitochondrial protein. Conclusion: Therefore, the present study reports, for the first time, the screening of phytobased bioactive CHL for preventing/limiting the extent of food-additive-induced genotoxicity and mitochondrial dysfunction and serves as an advanced therapeutic tool in the management of diabetes.