Abstract
Methylmercury (MeHg) is a strong soft electrophile chemical form ubiquitously found in environment and it can exhibit highly toxic effects in multiple organs. Previously, we observed that diphenyl diselenide [(PhSe) 2] reduced the deposition and toxicity of MeHg in brain, liver and kidney of mice. The present study was designed to investigate the possible interaction of (PhSe)2 with MeHg-induced mitochondrial dysfunction in rat liver slices in vitro. The liver slices were treated with MeHg (25 μM) and/or (PhSe)2 (0.5, 1, and 5 μM) for 30 min at 37 °C, then mitochondria were isolated from these slices, and the reactive oxygen species (ROS) formation, oxygen consumption, membrane potential (ΔΨm), mitochondrial metabolic function, nonprotein and total thiol content, and Glutathione peroxidase (GPx) activity were assessed. MeHg decreased the mitochondrial function by increasing ROS production, impairing oxygen consumption, and collapsing the ΔΨm. (PhSe)2 protected against the MeHg-induced ROS generation and prevented the decrease in the respiratory rate and in the mitochondrial metabolic function [measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction]. (PhSe)2 (0.5 μM) blunted the MeHg-induced ΔΨm collapse; however at 5 μM, (PhSe)2 alone decreased ΔΨm, yet partially protected the mitochondria from MeHg-induced depolarization. MeHg and (PhSe)2 (0.5 μM) alone or in combination had no effect on nonprotein and total thiol levels and on the GPx activity in mitochondria isolated from liver slices. The protection afforded by (PhSe)2 against the MeHg-induced mitochondrial dysfunction can be associated with (PhSe)2 metabolism to a selenol intermediate, forming inert complex(es) with MeHg, thus effectively decreasing its toxicity. Furthermore, the selenol intermediate of (PhSe)2 (selenophenol) may have direct antioxidant properties against peroxides induced by MeHg. In conclusion, the results demonstrate that low (PhSe)2 concentrations effectively prevent the MeHg-induced mitochondrial dysfunction in vitro.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 10437-10443 |
| Number of pages | 7 |
| Journal | Tetrahedron |
| Volume | 68 |
| Issue number | 51 |
| DOIs | |
| State | Published - Dec 23 2012 |
| Externally published | Yes |
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Keywords
- Methylmercury
- Mitochondrial dysfunction
- Mitochondrial permeability transition pore
- ROS production
- Seleno-organic compounds
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry
Cite this
Diphenyl diselenide prevents methylmercury-induced mitochondrial dysfunction in rat liver slices. / Dalla Corte, Cristiane L.; Soares, Félix A A; Aschner, Michael; Rocha, João B T.
In: Tetrahedron, Vol. 68, No. 51, 23.12.2012, p. 10437-10443.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Diphenyl diselenide prevents methylmercury-induced mitochondrial dysfunction in rat liver slices
AU - Dalla Corte, Cristiane L.
AU - Soares, Félix A A
AU - Aschner, Michael
AU - Rocha, João B T
PY - 2012/12/23
Y1 - 2012/12/23
N2 - Methylmercury (MeHg) is a strong soft electrophile chemical form ubiquitously found in environment and it can exhibit highly toxic effects in multiple organs. Previously, we observed that diphenyl diselenide [(PhSe) 2] reduced the deposition and toxicity of MeHg in brain, liver and kidney of mice. The present study was designed to investigate the possible interaction of (PhSe)2 with MeHg-induced mitochondrial dysfunction in rat liver slices in vitro. The liver slices were treated with MeHg (25 μM) and/or (PhSe)2 (0.5, 1, and 5 μM) for 30 min at 37 °C, then mitochondria were isolated from these slices, and the reactive oxygen species (ROS) formation, oxygen consumption, membrane potential (ΔΨm), mitochondrial metabolic function, nonprotein and total thiol content, and Glutathione peroxidase (GPx) activity were assessed. MeHg decreased the mitochondrial function by increasing ROS production, impairing oxygen consumption, and collapsing the ΔΨm. (PhSe)2 protected against the MeHg-induced ROS generation and prevented the decrease in the respiratory rate and in the mitochondrial metabolic function [measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction]. (PhSe)2 (0.5 μM) blunted the MeHg-induced ΔΨm collapse; however at 5 μM, (PhSe)2 alone decreased ΔΨm, yet partially protected the mitochondria from MeHg-induced depolarization. MeHg and (PhSe)2 (0.5 μM) alone or in combination had no effect on nonprotein and total thiol levels and on the GPx activity in mitochondria isolated from liver slices. The protection afforded by (PhSe)2 against the MeHg-induced mitochondrial dysfunction can be associated with (PhSe)2 metabolism to a selenol intermediate, forming inert complex(es) with MeHg, thus effectively decreasing its toxicity. Furthermore, the selenol intermediate of (PhSe)2 (selenophenol) may have direct antioxidant properties against peroxides induced by MeHg. In conclusion, the results demonstrate that low (PhSe)2 concentrations effectively prevent the MeHg-induced mitochondrial dysfunction in vitro.
AB - Methylmercury (MeHg) is a strong soft electrophile chemical form ubiquitously found in environment and it can exhibit highly toxic effects in multiple organs. Previously, we observed that diphenyl diselenide [(PhSe) 2] reduced the deposition and toxicity of MeHg in brain, liver and kidney of mice. The present study was designed to investigate the possible interaction of (PhSe)2 with MeHg-induced mitochondrial dysfunction in rat liver slices in vitro. The liver slices were treated with MeHg (25 μM) and/or (PhSe)2 (0.5, 1, and 5 μM) for 30 min at 37 °C, then mitochondria were isolated from these slices, and the reactive oxygen species (ROS) formation, oxygen consumption, membrane potential (ΔΨm), mitochondrial metabolic function, nonprotein and total thiol content, and Glutathione peroxidase (GPx) activity were assessed. MeHg decreased the mitochondrial function by increasing ROS production, impairing oxygen consumption, and collapsing the ΔΨm. (PhSe)2 protected against the MeHg-induced ROS generation and prevented the decrease in the respiratory rate and in the mitochondrial metabolic function [measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction]. (PhSe)2 (0.5 μM) blunted the MeHg-induced ΔΨm collapse; however at 5 μM, (PhSe)2 alone decreased ΔΨm, yet partially protected the mitochondria from MeHg-induced depolarization. MeHg and (PhSe)2 (0.5 μM) alone or in combination had no effect on nonprotein and total thiol levels and on the GPx activity in mitochondria isolated from liver slices. The protection afforded by (PhSe)2 against the MeHg-induced mitochondrial dysfunction can be associated with (PhSe)2 metabolism to a selenol intermediate, forming inert complex(es) with MeHg, thus effectively decreasing its toxicity. Furthermore, the selenol intermediate of (PhSe)2 (selenophenol) may have direct antioxidant properties against peroxides induced by MeHg. In conclusion, the results demonstrate that low (PhSe)2 concentrations effectively prevent the MeHg-induced mitochondrial dysfunction in vitro.
KW - Methylmercury
KW - Mitochondrial dysfunction
KW - Mitochondrial permeability transition pore
KW - ROS production
KW - Seleno-organic compounds
UR - http://www.scopus.com/inward/record.url?scp=84983721892&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983721892&partnerID=8YFLogxK
U2 - 10.1016/j.tet.2012.09.025
DO - 10.1016/j.tet.2012.09.025
M3 - Article
AN - SCOPUS:84983721892
VL - 68
SP - 10437
EP - 10443
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 51
ER -