Lead Reduces the Nephrotoxicity of Mercuric Chloride

Ewald, K.A.; Calabrese, E.J.

doi:10.1006/eesa.2000.2017

Cited by 8 publications

(1 citation statement)

References 26 publications

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“…These possibilities were ruled out by Tandon et al (1980), who showed that pretreatment with sodium chromate, p-aminophenol, sodium maleate, and uranyl acetate (nephrotoxic agents that do not induce metallothionein) also afforded protection from HgCl 2 -induced nephrotoxicity. Pretreatment by lead nitrate has also been shown to reduce the nephrotoxic effects of HgCl 2 in female mice (Ewald and Calabrese, 2001). In all of these studies, only renal injury was measured, and none of the studies investigated if animals receiving an ordinarily lethal dose of nephrotoxicant (HgCl 2 ) could survive if pretreated with glycerol, cadmium, low dose of HgCl 2 , or lead nitrate.…”

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confidence: 99%

Role of Tissue Repair in Survival from S-(1,2-Dichlorovinyl)-L-Cysteine-Induced Acute Renal Tubular Necrosis in the Mouse

Vaidya

Shankar²,

Lock³

et al. 2003

Toxicological Sciences

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S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), a model nephrotoxicant in mice, causes acute tubular necrosis and death at high doses. Our earlier studies revealed that renal tissue repair was critical for survival in mice with DCVC nephrotoxicity. The objective of this study was to investigate if increasing renal tissue repair could protect mice from the lethal outcome of DCVC. Male Swiss Webster (SW) mice were administered a low dose of DCVC (15 mg/kg, ip) 72 h before injection of a normally lethal dose of DCVC (75 mg/kg, ip); this resulted in 100% protection against the lethal effect of DCVC. Because DCVC caused approximately two fold decrease in cytosolic and mitochondrial beta-lyase activity, the possibility that DCVC protection may be caused by decreased bioactivation was examined. Mercuric chloride (HgCl2, 6 mg/kg), a nephrotoxicant with no effect on beta-lyase activity, was administered 96 h before a lethal dose of DCVC. This also resulted in 100% protection from the lethal effect of DCVC. In both studies total glutathione was unchanged at any time after the lethal dose of DCVC was administered, obviating the role of glutathione in protection. In both cases the augmented and sustained tissue repair induced by priming dose and documented by 3H-thymidine pulse labeling and immunocytochemistry for proliferating cell nuclear antigen resulted in 100% survival in spite of the extensive renal injury. These findings suggest that stimulation of renal tubular repair by the priming dose, through augmented cell division, and the resistance of new cells to mechanisms of progression of injury, underlies auto- and heteroprotection against DCVC. The molecular mechanisms may have potential application in pharmacotherapeutic intervention for treatment of acute renal failure.

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