Protective role of glutathione reductase in paraquat induced neurotoxicity
Само за регистроване кориснике
2012
Аутори
Đukić, MirjanaJovanović, Marina
Ninković, Milica
Stevanović, Ivana
Ilić, Katarina
Ćurčić, Marijana
Vekić, Jelena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Paraquat (PQ), a widely used herbicide is a well-known free radical producing agent. The mechanistic pathways of PQ neurotoxicity were examined by assessing oxidative/nitrosative stress markers. Focus was on the role of glutathione (GSH) cycle and to examine whether the pre-treatment with enzyme glutathione reductase (GR) could protect the vulnerable brain regions (VBRs) against harmful oxidative effect of PQ. The study was conducted on Wistar rats, randomly divided in five groups: intact-control group, (n = 8) and four experimental groups (n = 24). All tested compounds were administered intrastriatally (i.s.) in one single dose. The following parameters of oxidative status were measured in the striatum, hippocampus and cortex, at 30 min, 24 h and 7 days post treatment: superoxide anion radical (O-2(center dot-)), nitrate (NO3-). malondialdehyde (MDA), superoxide dismutase (SOD), total GSH (tGSH) and its oxidized, disulfide form (GSSG) and glutathione peroxidase (GPx). Results obtained... from the intact and the sham operated groups were not statistically different, confirming that invasive i.s. route of administration would not influence the reliability of results. Also, similar pattern of changes were observed between ipsi- and contra- lateral side of examined VBRs, indicating rapid spatial spreading of oxidative stress. Mortality of the animals (10%), within 24 h, along with symptoms of Parkinsonism, after awakening from anesthesia for 2-3 h, were observed in the PQ group, only. Increased levels of O2(center dot-), NO3- and MDA, increased ratio of GSSG/GSH and considerably high activity of GPx were measured at 30 min after the treatment. Cytotoxic effect of PQ was documented by drastic drop of all measured parameters and extremely high peak of the ratio GSSG/GSH at 24th hrs after the PQ i.s. injection. In the GR + PQ group, markedly low activity of GPx and low content of NO3- (in striatum and cortex) were measured during whole experiment, while increase value was observed only for O-2(center dot-), at 7th days. We concluded that oxidative/nitrosative stress and excitotoxicity are the most important events since the early stage of PQ induced neurotoxicity. Based on the ratio GSSG/GSH, the oxidation of GSH to GSSG is probably dominant way of GHS depletion and main reason for reduced antioxidative defense against PQ harmful oxidative effect. The GR pre-treatment resulted in the absence of Parkinson's disease-like symptoms and mortality of the rats. Additionally, oxidative/nitrosative stress did not developed, as well as almost diminished metabolism of the VBRs at 24th hours (as has been documented in the PQgroup) did not occurred in the GR + PQ suggesting a neuroprotective role for the GR in PQ induced neurotoxicity.
Кључне речи:
Paraquat / Neurotoxicity / Glutathione / Glutathione reductaseИзвор:
Chemico-Biological Interactions, 2012, 199, 2, 74-86Издавач:
- Elsevier Ireland Ltd, Clare
Финансирање / пројекти:
DOI: 10.1016/j.cbi.2012.05.008
ISSN: 0009-2797
PubMed: 22721943
WoS: 000309331700003
Scopus: 2-s2.0-84864039375
Институција/група
PharmacyTY - JOUR AU - Đukić, Mirjana AU - Jovanović, Marina AU - Ninković, Milica AU - Stevanović, Ivana AU - Ilić, Katarina AU - Ćurčić, Marijana AU - Vekić, Jelena PY - 2012 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1653 AB - Paraquat (PQ), a widely used herbicide is a well-known free radical producing agent. The mechanistic pathways of PQ neurotoxicity were examined by assessing oxidative/nitrosative stress markers. Focus was on the role of glutathione (GSH) cycle and to examine whether the pre-treatment with enzyme glutathione reductase (GR) could protect the vulnerable brain regions (VBRs) against harmful oxidative effect of PQ. The study was conducted on Wistar rats, randomly divided in five groups: intact-control group, (n = 8) and four experimental groups (n = 24). All tested compounds were administered intrastriatally (i.s.) in one single dose. The following parameters of oxidative status were measured in the striatum, hippocampus and cortex, at 30 min, 24 h and 7 days post treatment: superoxide anion radical (O-2(center dot-)), nitrate (NO3-). malondialdehyde (MDA), superoxide dismutase (SOD), total GSH (tGSH) and its oxidized, disulfide form (GSSG) and glutathione peroxidase (GPx). Results obtained from the intact and the sham operated groups were not statistically different, confirming that invasive i.s. route of administration would not influence the reliability of results. Also, similar pattern of changes were observed between ipsi- and contra- lateral side of examined VBRs, indicating rapid spatial spreading of oxidative stress. Mortality of the animals (10%), within 24 h, along with symptoms of Parkinsonism, after awakening from anesthesia for 2-3 h, were observed in the PQ group, only. Increased levels of O2(center dot-), NO3- and MDA, increased ratio of GSSG/GSH and considerably high activity of GPx were measured at 30 min after the treatment. Cytotoxic effect of PQ was documented by drastic drop of all measured parameters and extremely high peak of the ratio GSSG/GSH at 24th hrs after the PQ i.s. injection. In the GR + PQ group, markedly low activity of GPx and low content of NO3- (in striatum and cortex) were measured during whole experiment, while increase value was observed only for O-2(center dot-), at 7th days. We concluded that oxidative/nitrosative stress and excitotoxicity are the most important events since the early stage of PQ induced neurotoxicity. Based on the ratio GSSG/GSH, the oxidation of GSH to GSSG is probably dominant way of GHS depletion and main reason for reduced antioxidative defense against PQ harmful oxidative effect. The GR pre-treatment resulted in the absence of Parkinson's disease-like symptoms and mortality of the rats. Additionally, oxidative/nitrosative stress did not developed, as well as almost diminished metabolism of the VBRs at 24th hours (as has been documented in the PQgroup) did not occurred in the GR + PQ suggesting a neuroprotective role for the GR in PQ induced neurotoxicity. PB - Elsevier Ireland Ltd, Clare T2 - Chemico-Biological Interactions T1 - Protective role of glutathione reductase in paraquat induced neurotoxicity VL - 199 IS - 2 SP - 74 EP - 86 DO - 10.1016/j.cbi.2012.05.008 ER -
@article{ author = "Đukić, Mirjana and Jovanović, Marina and Ninković, Milica and Stevanović, Ivana and Ilić, Katarina and Ćurčić, Marijana and Vekić, Jelena", year = "2012", abstract = "Paraquat (PQ), a widely used herbicide is a well-known free radical producing agent. The mechanistic pathways of PQ neurotoxicity were examined by assessing oxidative/nitrosative stress markers. Focus was on the role of glutathione (GSH) cycle and to examine whether the pre-treatment with enzyme glutathione reductase (GR) could protect the vulnerable brain regions (VBRs) against harmful oxidative effect of PQ. The study was conducted on Wistar rats, randomly divided in five groups: intact-control group, (n = 8) and four experimental groups (n = 24). All tested compounds were administered intrastriatally (i.s.) in one single dose. The following parameters of oxidative status were measured in the striatum, hippocampus and cortex, at 30 min, 24 h and 7 days post treatment: superoxide anion radical (O-2(center dot-)), nitrate (NO3-). malondialdehyde (MDA), superoxide dismutase (SOD), total GSH (tGSH) and its oxidized, disulfide form (GSSG) and glutathione peroxidase (GPx). Results obtained from the intact and the sham operated groups were not statistically different, confirming that invasive i.s. route of administration would not influence the reliability of results. Also, similar pattern of changes were observed between ipsi- and contra- lateral side of examined VBRs, indicating rapid spatial spreading of oxidative stress. Mortality of the animals (10%), within 24 h, along with symptoms of Parkinsonism, after awakening from anesthesia for 2-3 h, were observed in the PQ group, only. Increased levels of O2(center dot-), NO3- and MDA, increased ratio of GSSG/GSH and considerably high activity of GPx were measured at 30 min after the treatment. Cytotoxic effect of PQ was documented by drastic drop of all measured parameters and extremely high peak of the ratio GSSG/GSH at 24th hrs after the PQ i.s. injection. In the GR + PQ group, markedly low activity of GPx and low content of NO3- (in striatum and cortex) were measured during whole experiment, while increase value was observed only for O-2(center dot-), at 7th days. We concluded that oxidative/nitrosative stress and excitotoxicity are the most important events since the early stage of PQ induced neurotoxicity. Based on the ratio GSSG/GSH, the oxidation of GSH to GSSG is probably dominant way of GHS depletion and main reason for reduced antioxidative defense against PQ harmful oxidative effect. The GR pre-treatment resulted in the absence of Parkinson's disease-like symptoms and mortality of the rats. Additionally, oxidative/nitrosative stress did not developed, as well as almost diminished metabolism of the VBRs at 24th hours (as has been documented in the PQgroup) did not occurred in the GR + PQ suggesting a neuroprotective role for the GR in PQ induced neurotoxicity.", publisher = "Elsevier Ireland Ltd, Clare", journal = "Chemico-Biological Interactions", title = "Protective role of glutathione reductase in paraquat induced neurotoxicity", volume = "199", number = "2", pages = "74-86", doi = "10.1016/j.cbi.2012.05.008" }
Đukić, M., Jovanović, M., Ninković, M., Stevanović, I., Ilić, K., Ćurčić, M.,& Vekić, J.. (2012). Protective role of glutathione reductase in paraquat induced neurotoxicity. in Chemico-Biological Interactions Elsevier Ireland Ltd, Clare., 199(2), 74-86. https://doi.org/10.1016/j.cbi.2012.05.008
Đukić M, Jovanović M, Ninković M, Stevanović I, Ilić K, Ćurčić M, Vekić J. Protective role of glutathione reductase in paraquat induced neurotoxicity. in Chemico-Biological Interactions. 2012;199(2):74-86. doi:10.1016/j.cbi.2012.05.008 .
Đukić, Mirjana, Jovanović, Marina, Ninković, Milica, Stevanović, Ivana, Ilić, Katarina, Ćurčić, Marijana, Vekić, Jelena, "Protective role of glutathione reductase in paraquat induced neurotoxicity" in Chemico-Biological Interactions, 199, no. 2 (2012):74-86, https://doi.org/10.1016/j.cbi.2012.05.008 . .