Reactive oxygen species induced injury

Lead-induced hyperuricemia may contribute to chronic lead nephropathy. Uric acid per se induces endothelial cell injury, renal microvascular disease, and hypertension, at least in part mediated by oxidative stress [38]. Independent of uric acid, reactive oxygen species induced by lead have been imphcated in endothelial cell injury, increased vascular reactivity, and the production of hypertension in humans and experimental animals [39]. 

Heat shock proteins (HSPs) are a family of proteins expressed in almost all organisms from prokaryotes to humans. HSPs were originally described about four decades ago as proteins that were induced in the Drosophila melanogaster in response to a heat stress and hence derive the name HSR However, research over the years has uncovered these proteins to have a multitude of functions. Primarily, all HSPs act as molecular chaperons and assist in proper folding of naive proteins. Furthermore, HSPs have important roles in cellular processes including cell survival, inflammation, immunity, ion channel repair, and others. HSPs are also induced by a variety of stressors. Reactive oxygen species, cytotoxic injury, necrosis, ultraviolet radiation, metals, and many others are some examples. 

Figure 4.2. Diagram outlining the pathogenesis of liver fibrosis. Injury to parenchymal cells (PC) results in the activation of Kupffer cells (KC) and sinusoidal endothelial cells (SEC) and the recruitment of inflammatory cells (IC). These cells release cytokines, growth factors and reactive oxygen species that induce activation and proliferation of hepatic stellate cells (HSC). HSCs gradually transform into myofibroblasts (MF), the major producers of extracellular matrix (ECM) proteins.

Sipes IG, El Sisi AE, Sim WW, et al. 1991. Reactive oxygen species in the progression of CCh -induced liver induced liver injury. In Biol Reactive Intermediates IV, Plenum Press, New York, NY 489-497. 

Concomitant expression of metallothioneins (MTs) and metalloproteinases (MMPs) occurs in skeletal muscle that has experienced an injury (Lecker et al. 2004 Warren et al. 2007). MTs are small (12-14 kDa), ubiquitous, cysteine-rich, zinc-binding proteins which are primarily produced in the liver and released into the circulation (Tapiero and Tew 2003). Upon release into the circulation these proteins play a pivotal role in cellular processes to render protection to all tissues of the body. In skeletal muscle, MTs initiate anti-inflammatory and anti-apoptotic signaling cascades, reduce reactive oxygen species (ROS)-induced cytotoxicity, protect against ROS-induced DNA degradation, and maintain zinc homeostasis... 

AP-induced toxicity and measurement of cell survival/injury were performed as described in detail elsewhere.1011 Briefly, 6-day-old cells were exposed to fresh solutions of either Ap25 35 or Ap, 42 for 24 h, in the presence or absence of different drugs. Cell survival and extent of cell death were determined using MTT and Sytox green assays, respectively. Measurement of intracellular reactive oxygen species was determined by dichlorofluorescein (DCF) fluorescence assay, as described previously.23... 

The reaction that produces NAPQI generates superoxide anions as a by-product. Interactions of NAPQI with other cellular molecules also generate reactive oxygen species, leading to oxidative stress on the hepatocyte (Zimmerman, 1999 Dahm and Jones, 1996). The role of calcium and Kupffer cell activation have been impUcated as contributing factors for acetaminophen-induced liver injury by producing reactive nitrogen species (Treinen-Moslen, 2001). 

Shi X., Ding M., Chen F., Wang L., Rojanasakul Y., Vallyathan V., and Castranova V. (2001) Reactive oxygen species and molecular mechanisms of silica-induced lung injury. J. Environ. Pathol. Toxicol. Oncol. 20(suppl. 1), 85-93. 

It has been shown that the renal bioactivation of xenobiotics such as the herbicides paraquat and diquat [10, 111, 112], and of p-lactams such as cephaloridine and cefsulodin [10, 40, 41] or the antitumor agent adriamycin [113, 114] can induce the generation of reactive oxygen species (oxidative stress) which can be involved in alterations of the structure and functions of cell membranes, cytoskeletal injury, mutagenicity, carcinogenicity, and cell necrosis [115-117]. 

Reactive oxygen species (ROS), such as superoxide anion and hydroxy radical, induce lipid peroxidation (LPO) which injuries cell membranes. 

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