The Mechanisms Of Coenzyme NADH In Cytoprotection Against Antineoplastic Agent-induced Apoptotic Damage

J3ackground Chemotherapy plays an important role in the comprehensive treatment of cancer. Chemotherapy has provided better clinical remission and cure for patients with some malignant tumors, such as skin cancer, chorioepithelioma and retioblastoma. However, Chemotherapy for cancer often has severe side effects that limit its efficacy, such as myelosuppression, mucositis, nephrotoxicity, neurotoxicity and cardiotoxicity. In fact, chemotherapy involves a balance between maximizing tumor eradication and minimizing normal tissue damage. If response rates to antineoplastic agents are to be improved, normal tissues need to be protected from the immediate and delayed effects of cytotox.ic agents. As any cytoprotector in chemotherapy, it should be shown to reduce normal tissue damage from these cytotoxic therapies and increase the therapeutic index and efficacy of treatment. The coenzyme NADH helps many enzymes involved in energy production within mitochondria and metabolic reaction in cells. NADH plays a vital role in the generation of adenosine triphosphate. NADH is crucial in process of repairing wounded cells. NADH is the most biologically potent antioxidant in nature and has the strongest positive effect in fighting the damage of free radicals. NADH increases the body抯 creation of depleted brain chemicals called neurotransmitters. NADH not only alleviated the impairment in motor skills caused by Parkinson抯, but also effectively treated the corresponding cognitive dysfunction. Apoptosis is essential in many physiological and pathological processes. Apoptosis comes from the mode of cell death that is triggered by a variety of antitumor drugs. In many types of antineoplastic -9- induced damages, toxic effects are thought to happen by effects on the mitochondria. Mitochondria are presented as the important executioner of apoptosis. Anti-apoptotic members probably function as rnitochondia membrane stabilizing molecular. Caspases zymogens are seen to be activated during apoptosis. Specific Caspases inhibitors prevent the development of apoptosis. New consideration and methods will be provided to ease chemotherapy-induced apoptotic damage by regulating apoptosis. Objective The study was intended to clarify the molecular mechanisms of coenzyme NADH in cytoprotection against antineoplastic agent-induced apoptotic damage. The apoptotic damage of antineoplastic agents in vitro, the ?mitochondria regulation mechanism of coenzyme NADH in cytoprotection and the mecahanism of NADH against Adriamycin-induced cardiotoxicity were observed. New chemotherapeutic strategy was provided to develop the latest cytoprotector in chemotherapy, establish new usage of coenzyme NADH, solve the difficult problem in chemotherapy-how to lessen and avoid the chemotherapy-induced toxicity of normal tissues and cells as far as possible. Methods 1. MTT colorimetric assay was applied to detect cytotoxicity of DDP in human L02 ?hepatocyte line, proliferation activity of cells and cytotoxicity of DDP influenced by NADH. Apoptosis rate of cells was examined by flow cytometry. Apoptotic alteration. was observed with TIJNEL dyeing by fluorescence microscope. Ultrastructure of hepatocyte was observed by transmission and scanning electron nlicroscope. The inhibition of coenzyrne NADH in apoptosis induced by DDP was understood.