Oxidative stress renal toxicity

Iqbal, M. and Athar, M., Attenuation of iron-nitrilotriacetate (Fe-nta)-mediated renal oxidative stress, toxicity and hyperproliferative response by the prophylactic treatment of rats with garlic oil, Food Chem. Toxicol., 36, 485M95, 1998. 

Kumar, O., Sugendran, K., Vijayaraghavan, R. (2003). Oxidative stress associated hepatic and renal toxicity induced by ricin in mice. Toxicon 41 333-8. 

The data indicate that zinc-induced metallothionein binds mercury in the renal cortex and shifts the distribution of mercury from its site of toxicity at the epithelial cells of the proximal tubules. Thus, the renal content of mercury is increased, yet less is available to cause toxicity. In contrast, the renal toxicity of mercuric chloride is exacerbated in zinc-deficient animals (Fukino et al. 1992). In the zinc-deficient state, less mercury accumulates in the kidneys, but the toxicity is greater. The mechanism of the protection appears to involve more than simply a redistribution of renal mercury, because in the absence of mercury exposure, zinc deficiency increases renal oxidative stress (increased lipid peroxidation, decreased reduced ascorbate). When mercury exposure occurs, the oxidative stress is compounded (increased lipid peroxidation and decreased glutathione and glutathione peroxidase). Thus, zinc appears to affect the biochemical protective mechanisms in the kidneys as well. 

Wilmes A, Crean D, Aydin S, Pfaller W, Jennings P, Leonard MO (2011) Identification and dissection of the Nrf2 mediated oxidative stress pathway in human renal proximal tubule toxicity. Toxicol In Vitro 25(3) 613-622. doi 10.1016/j.tiv.2010.12.009... 

The potential protective effect of 2-mercaptoethane sulfonate, which reduces oxidative stress by increasing free thiols in the kidney, on renal toxicity and carcinogenicity induced by ochratoxin A has been examined in a long-term rat study. 2-Mercaptoethane sulfonate significantly reduced karyomegaly but did not reduce the incidence of renal tumours (Pfohl-Leszkowicz Manderville, 2007). 

Mercury toxicity is related to the induction of oxidative stress, as revealed by the decrease in antioxidant enzymes as glutathione S-transferase (Reddy et al. 1981). Examining interactions of purified Mn-superoxide dismutase (1 fM) with HgCl2 indicated that mercury ions suppressed Mn-superoxide dismutase activity by reduction of the native form (Shimojo et al. 2002). Due to the minimal hepatic accumulation of inorganic mercury after the subcutaneous application of HgCl2 (0.25-3 mg/kg) to mice the hepatic Mn-superoxide dismutase might be unaffected while the renal enzyme due to a 34-75 times higher accumulation of mercury in the kidney was decreased in a dose-dependent manner. 

I. Mechanism of toxicity. Arsine is a potent hemolytic agent. Recent investigations suggest that hemolysis occurs en arsine interacts with heme to fomi a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Note Arsenite and other oxidized fomis of arsenic do not cause hemolysis. Deposition of massive amounts of hemoglobin in the renal tubule can cause acute renal injury. Massive hemolysis also decreases systemic oxygen delivery and creates hypoxic stress, and arsine and/or its reaction products exert direct cytotoxic effects on multiple organs. 

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