The need for rational prescribing, that is, the selection of the most appropriate therapeutic reg... more The need for rational prescribing, that is, the selection of the most appropriate therapeutic regimen for a specific patient, is greater than ever. For example, a recent study identified physicians' poor prescribing performance as the source for over 70% of clinically significant medication errors in a tertiary-care setting. 1 This may not be surprising given that physicians are expected to incorporate vast amounts of critical information on an ever-increasing number of prescription medications, over-the-counter medications, vitamins, and herbal supplements into prescribing in real time. New data on genetically determined differences in drug action and drug metabolism become available on a daily basis. The problem is further confounded by an aging population with multiple medical problems taking multiple drugs, vitamins, and herbal preparations. Limitations imposed by formulary requirements of health insurance plans and hospital systems further complicate the matter. At the same time, public aware-From the
ROS, RNS, BRIs and ROS-RNS hybrids are produced during drug or chemical metabolism in vivo. These... more ROS, RNS, BRIs and ROS-RNS hybrids are produced during drug or chemical metabolism in vivo. These reactive species are instrumental to the culmination of cellular oxidative stress (OS). OS, once turned on, does not spare any vital intracellular macromolecule, such as glutathione, DNA, RNA, proteins, enzymes, lipids and ATP. Since concentration gradients of such components are very delicately balanced for normal cellular functioning, a gross perturbation leads to cell injury and cell death. Abundant evidence now suggests that intracellular antioxidants keep OS in check and maintain homeostasis. Our laboratory has focused on the role of OS in orchestrating various forms of cell death during drug and chemically-induced target organ toxicity and their counteraction by various natural or synthetic antioxidants in in vivo models. Despite complexity of the in vivo models, results show that metabolism of xenobiotics are invariably associated with different degrees of OS and natural antioxidants such as grape seed extract, bitter melon extract (Momordica charantia) and N-acetylcysteine (NAC) which were very effective in counteracting organ toxicities by minimizing events linked to OS (lipid peroxidation and total glutathione), and CAD-mediated DNA fragmentation. Phytoextract exposure rescued cells from toxic assaults, protected genomic integrity, and minimized apoptotic, necrotic and apocrotic (oncotic necrosis) cell deaths. Pre-exposure mode was more effective than post-exposure route. Overall scenario suggests that OS may have been the prime modulator of death and/or survival programs, whereas, antioxidants may have imparted a dual role in either erasing death signals or reviving survival signals, and a combination of antioxidants may be more beneficial than a single entity to influence a number of intracellular events operating simultaneously to neutralize chaotic toxicological consequences.
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