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. 2013:2013:983821.
doi: 10.1155/2013/983821. Epub 2013 Dec 29.

Effects of diphenyl diselenide on methylmercury toxicity in rats

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Effects of diphenyl diselenide on methylmercury toxicity in rats

Cristiane L Dalla Corte et al. Biomed Res Int. 2013.

Abstract

This study investigates the efficacy of diphenyl diselenide [(PhSe)2] in attenuating methylmercury- (MeHg-)induced toxicity in rats. Adult rats were treated with MeHg [5 mg/kg/day, intragastrically (i.g.)] and/ or (PhSe)2 [1 mg/kg/day, intraperitoneally (i.p.)] for 21 days. Body weight gain and motor deficits were evaluated prior to treatment, on treatment days 11 and 21. In addition, hepatic and cerebral mitochondrial function (reactive oxygen species (ROS) formation, total and nonprotein thiol levels, membrane potential (ΔΨm), metabolic function, and swelling), hepatic, cerebral, and muscular mercury levels, and hepatic, cerebral, and renal thioredoxin reductase (TrxR) activity were evaluated. MeHg caused hepatic and cerebral mitochondrial dysfunction and inhibited TrxR activity in liver (38,9%), brain (64,3%), and kidney (73,8%). Cotreatment with (PhSe)2 protected hepatic and cerebral mitochondrial thiols from depletion by MeHg but failed to completely reverse MeHg's effect on hepatic and cerebral mitochondrial dysfunction or hepatic, cerebral, and renal inhibition of TrxR activity. Additionally, the cotreatment with (PhSe)2 increased Hg accumulation in the liver (50,5%) and brain (49,4%) and increased the MeHg-induced motor deficits and body-weight loss. In conclusion, these results indicate that (PhSe)2 can increase Hg body burden as well as the neurotoxic effects induced by MeHg exposure in rats.

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Figures

Figure 1
Figure 1
Effect of MeHg and/or (PhSe)2 on the body weight gain in adult rats. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test.
Figure 2
Figure 2
Hg content in liver (a), brain (b), and muscle (c) of rats exposed to MeHg and/or (PhSe)2. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test. (#) represents P < 0.05 as compared to MeHg by Mann-Whitney test.
Figure 3
Figure 3
Rotarod and open field tests in rats exposed to MeHg and/or (PhSe)2. The number of falls (a) and latency for the first fall (b) ambulation (crossing) (a) and rearing (b) were recorded. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Kruskal-Wallis test followed by multiple comparison test. (#) represents P < 0.05 as compared to (PhSe)2 by Kruskal-Wallis test followed by multiple comparison test.
Figure 4
Figure 4
MTT reduction in liver (a) and brain (b) mitochondria of rats exposed to MeHg and/or (PhSe)2. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test.
Figure 5
Figure 5
Total and nonprotein thiol content in liver (a), (c) and brain (b), (d) mitochondria of rats exposed to MeHg and/or (PhSe)2. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test.
Figure 6
Figure 6
Mitochondrial swelling in liver (a) and brain (b) of rats exposed to MeHg and/or (PhSe)2. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test.
Figure 7
Figure 7
ROS production (H2-DCFH oxidation) in liver (a) and brain (b) mitochondria of rats exposed to MeHg and/or (PhSe)2. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test.
Figure 8
Figure 8
Mitochondrial depolarization in liver (a), (c) and brain (b), (d) of rats exposed to MeHg and/or (PhSe)2. Figures (a) and (b) show mitochondrial membrane potential (AFU). Figures (c) and (d) show mitochondrial ΔΨm. ΔΨm1 = delta of fluorescence before (time 0) and after addition of mitochondria (time 150 seconds) and ΔΨm2 = delta of fluorescence before (time 150 seconds) and after addition of 2,4 DNP (time 300 seconds). Data are expressed as mean ± S.D., n = 4.
Figure 9
Figure 9
TrxR activity in liver (a), kidney (b), and brain (c) of rats exposed to MeHg and/or (PhSe)2. Data are expressed as mean ± S.D., n = 4. (∗) represents P < 0.05 as compared to controls by Mann-Whitney test. (#) represents P < 0.05 as compared to controls by Mann-Whitney test.

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