Drug-Drug Interactions with Relevance to Drug Induced Mitochondrial Toxicity and Accelerated Global Chronic Diseases

Drug therapy to stabilize insulin resistance and various chronic diseases that reverse cell senescence and apoptosis has been implemented in various global populations. The need to optimize drug therapy and improve therapeutic outcomes has become of major concern with relevance to alarming reports of drug-drug interactions or drug-disease interactions with relevance to the global chronic disease epidemic. In diseases of the heart, brain and liver cell senescence is now connected to mitochondrial apoptosis with nutrition of major importance in the maintenance of mitochondrial biogenesis and the prevention of NAFLD and obesity. The search for specific genes that maintain mitochondria biogenesis has identified the anti-aging gene Sirtuin 1 (Sirt 1) as the gene involved in mitochondrial biogenesis. Sirt 1 is a NAD+ dependent class III histone deacetylase activity involved in the regulation of metabolic activity, insulin resistance and inflammatory processes and is now important to drug therapy and metabolism with relevance to prevention of drug-drug interactions. Sirt 1is involved in the deacetylation of the pregnane X receptor that is critical to drug metabolism and regulation of other transcription factors (deacetylation) are also linked to hepatic glucose, fatty acid and caffeine metabolism. Nutritional interventions are required to optimize drug therapy and improve therapeutic outcomes to reverse drug-drug interactions or drug-disease interactions in the current global chronic disease epidemic. Low calorie diets that activate Sirt 1 have become critical to prevent NAFLD, cardiovascular disease and neurodegeneration with consumption Sirt 1 activators important to maintain drug therapy and metabolism. Unhealthy diets that reduce drug metabolism increases the risk for chronic diseases with relevance to drug induced mitochondrial apoptosis in the liver, pancreas, heart and brain. In the developing world caffeine consumption should be assessed with relevance to the elevated levels of xenobiotic and LPS that may inactivate drug metabolism and accelerate drug induced mitochondrial apoptosis in these populations.