Pathogenesis of non steroidal anti inflammatory drug NSAID induced renal damage

Abstract

The ability to relieve pain is one of the greatest gifts of modern medicine to human beings. There are two major types of pain killers or analgesics opioids and nonsteroidal anti-inflammatory drugs (or NSAIDs). Indomethacin-induced oxidative stress in the kidney activates several downstream events. These may include activation of nuclear factor kappa B (NF-and#954;B) and mitogen-activated protein kinase (MAPK) signaling pathways, induction of stress proteins such as heme oxygenase 1 (HO-1) and heat shock protein 70 (hsp70), induction of endoplasmic reticulum stress (ER stress) response and initiation of apoptotic events in the kidney. These events may contribute to NSAID-induced renal dysfunction. Zinc, a known antioxidant, may attenuate these drug-induced changes; such effects may account for its protective effect against indomethacin-induced renal dysfunction. The major goal of the studies described was to elucidate various biochemical events that occur in the rat kidney in response to the administration of indomethacin, so as to gain a better understanding of the mechanisms that may contribute to NSAID-induced renal dysfunction. It was also aimed to determine the possible mechanisms by which zinc attenuated indomethacin-induced renal dysfunction. The specific aims of this study therefore were: 1. To determine associations among markers of indomethacin-induced oxidative stress in the rat kidney and the effect of such stress on nuclear factor kappa B (NF-and#954;B) signaling 2. To determine the effect of indomethacin on stress proteins (heat-shock protein [hsp70]and heme oxygenase 1 [HO-1]) in the rat kidney and related signaling events 3.To determine associations among markers of indomethacin-induced oxidative stress in renal mitochondria and the effect of indomethacin on endoplasmic reticulum stress and apoptosis 4. To determine the effect of zinc pretreatment on indomethacin-induced changes in the rat kidney. newline newline newline newline newline newline newline newline newline