Effect Of 1-azabenzanthrone,[Pt~ⅡCIL(DMSO)],Rutin And Some Organic Solvents On Mitochondria Dysfunction

Mitochondria are fascinating organelles that play a central role in cellular metabolism. The interest in mitochondria had waned since their identification. Mitochondrial dysfunction is linked to a range of pathologies, including cancer, neurodegenerative disorders, premature aging, diabetes and muscular diseases. At present, there is a considerable public and scientific interest in utilizing nature products for the treatment and prevention of various diseases.Mitochondria targeted anticancer agents (mitocans) open new perspectives for their chemotherapy application. Many of the agents with anti-cancer activity that act on mitochondria, mitocans, hold a substantial promise to be developed into efficient anti-cancer drugs, based on their selectivity for cancer cells. Identification of their effect on mitochondria may help us to better understand the drug’s mechanism and to improve their design plan.This thesis includes four chapters:In chapter 1, a brief survey of recent development in the field of mitochondrial research has been given. Mitochondria have emerged as an intriguing target for anti-cancer drugs, inherent to vastmajority if not all types of tumours. Drugs that target mitochondria and exert anti-cancer activity have become a focus of recent research due to their great clinical potential. All data will help us learn more about a concisemanner the classification of compounds that hold a considerable promise as potential anti-cancer drugs.In chapter 2, we measure the effect of two anticancer agents 1-azabenzanthrone (L) and [PtⅡC1L(DMSO)] on mitochondrial function. We observe that 1-azabenzanthrone (L) and [PtⅡC1L(DMSO)] can significantly induce the mitochondrial swelling, collapse membrane potential, affect respiration. These results indicate that apoptosis induced by two anticancer agents may involve with mitochondrial pathway.In chapter 3, the results show that rutin can protect Ca2+-induced mitochondrial swelling, decrease membrane potential and affect the respiration of mitochondria. Meanwhile, rutin does not have a direct effect on the mitochondrial permeability transition pore. The influence of rutin on mitochondrial function is not obviously.In chapter 4, we discuss the toxicity of organic solvents:DMSO、DMF、EtOH on the function of mitochondria isolated from rat livers. Our results will help us learn more about their toxicity at subcellular (mitochondrial) level. Organic solvents toxicity on mitochondria indicates that the organic solvents require to be further improved before they can be safely used in clinic.