Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters

Hirata, Miyuki; Tanaka, Akiyo; Hisanaga, Akira; Ishinishi, Noburu

doi:10.1016/0041-008x(90)90342-r

Cited by 50 publications

(28 citation statements)

References 22 publications

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“…In both cases, the increase in GSH is likely to be a response caused by increased exposure to toxins. On the other hand, pretreatment with GSH depletors impairs arsenic methylation in animal tissue (30)(31)(32). While a higher MMA:DMA ratio suggests modulation of the second methylation step, and the animal studies have suggested that GSH depletion mainly affects the first methylation reaction, these inconsistencies may be due to differences in arsenic methylation that exist between animals and humans.…”

Section: Discussionmentioning

confidence: 82%

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

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Section: Discussionmentioning

confidence: 82%

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

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“…Conversely, it has been reported that arsenic toxicity was potentiated after pretreatment with drugs that produced GSH depletion (12). This enhancement of arsenic-induced injury in GSH-depleted animals, may result from impaired methylation.…”

Section: Introductionmentioning

confidence: 98%

“…It has been shown that methylation renders arsenic less reactive with tissue and therefore facilitates its elimination from the body (14). Arsenic tissue accumulation has been demonstrated in blood, liver, and kidney of hamsters pretreated with BSO (12), and in liver of rats pretreated with phorone (a depletor of GSH concentrations) (13).…”

Section: Introductionmentioning

confidence: 99%

“…This enhancement of arsenic-induced injury in GSH-depleted animals, may result from impaired methylation. Pretreatment with depletors of GSH levels in hamsters (12), rat (13), and rat tissue slices (6), impaired the methylation of inorganic arsenic. It has been shown that methylation renders arsenic less reactive with tissue and therefore facilitates its elimination from the body (14).…”

Section: Introductionmentioning

confidence: 99%

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Arsenic Increased Lipid Peroxidation in Rat Tissues by a Mechanism Independent of Glutathione Levels

Ramos¹,

Carrizales²,

Yáñez³

et al. 1995

Environmental Health Perspectives

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The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSHI inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels,but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart. -Environ Health Perspect 103(Suppl 1): 85-88 (1995)

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“…Several studies have shown that HgCl2 and NaAsO2 accumulate in specific zones of the kidney cortex. HgCl2 first accumulates in the straight proximal tubule (1), while NaAsO2 initially affects the convoluted proximal tubule (2). A number of mechanisms of uptake have been postulated; however, the actual process is as yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Glutathione Effects on Toxicity and Uptake of Mercuric Chloride and Sodium Arsenite in Rabbit Renal Cortical Slices

Burton¹,

Hatlelid²,

Divine³

et al. 1995

Environmental Health Perspectives

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The mechanism of renal uptake of nephrotoxic heavy metals such as HgCI2 and NaAsO2 is not clear. The metals are known to react with endogenous sulfhydryls such as glutathione (GSH), so metal-GSH conjugates may be delivered to the kidney. To study this possibility, renal cortical slices from male New Zealand white rabbits were incubated with 104 M HgCI2 or 10-3 M NaAsO2 ± stoichiometric amounts (1-3x) of GSH; or synthetic metal-GSH conjugates [104 M Hg(SG)2 or 1 M As(SG)31. Incubations were performed at 370C in DME-F12 buffer (95/5 02/CO2) for 8 hr. Hg(SG)2 reduced slice K+/DNA content, as an indicator of viability, significantly less than HgCI2. As(SG)3 exhibited a 2-hr delay in K+/DNA content reduction compared to NaAsO2. This delay in toxicity was not correlated to changes in uptake. Arsenic and mercury accumulation, determined by protoninduced X-ray emission, were also identical between the metal salts and the metal-GSH conjugates. Exogenous GSH decreased HgCI2 cytotoxicity and was correlated to a decrease in Hg accumulation in the slice. Exogenous GSH had limited if any protective effects against cytotoxicity by NaAsO2 and a decrease in As accumulation was not observed. Complex metal-GSH interactions appear to exist and impact on the uptake and toxicity of these metals. -Environ Health Perspect 103(Suppl 1): 81-84 (1995)

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Effects of glutathione depletion on the acute nephrotoxic potential of arsenite and on arsenic metabolism in hamsters

Cited by 50 publications

References 22 publications

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Arsenic Increased Lipid Peroxidation in Rat Tissues by a Mechanism Independent of Glutathione Levels

Glutathione Effects on Toxicity and Uptake of Mercuric Chloride and Sodium Arsenite in Rabbit Renal Cortical Slices

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