The effects of low-doses of microcystin-leucinearginine （ MC-LR ） exposure on neurobehaviors and N-acetylaspartate （NAA） expression in the hippocampus of rats were investigated. After male Sprague-Dawley （SD） ra...The effects of low-doses of microcystin-leucinearginine （ MC-LR ） exposure on neurobehaviors and N-acetylaspartate （NAA） expression in the hippocampus of rats were investigated. After male Sprague-Dawley （SD） rats were treated intra-gastrically with different doses of MC-LR for 90 d, the locomotor activity, spatial learning and memory function were evaluated in the rats after treatment using open field tests and Morris water maze tests. The results show that MC-LR exposure can lead to impairment of the spatial learning capacity and locomotor activity in rats at the dose of 2. 00 p,g/kg. The levels of NAA in the hippocampus were measured by magnetic resonance spectroscopy （MRI）. A significant decrease of NAA/Cr ratio （ P 〈 0. 05） was observed in the hippocampous. This study indicates that intra-gastrical exposure to low-doses of MC-LR has adverse effects on neuronal behavior and NAA levels in the hippocampous.展开更多
Microcystin-LR （MC-LR） is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen （Group 2B） by the International Agency for Research on Cancer. However, the mechan...Microcystin-LR （MC-LR） is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen （Group 2B） by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human-hamster hybrid （AL） cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher （p 〈 0.01） in AL ceUs exposed to a cytotoxic concentration （1 μmol/L） of MC-LR for 30 days than in untreated control ceils, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide （NO） production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor NC-methyl-L-arginine （L-NMMA）, which suppressed MC-LR- induced mutations as well. The survival of mitochondrial DNA-depleted （pO） AL ceils was markedly decreased by MC-LR treatment compared to that in AL cells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis.展开更多
基金The National Natural Science Foundation of China(No.8107225881273123)
文摘The effects of low-doses of microcystin-leucinearginine （ MC-LR ） exposure on neurobehaviors and N-acetylaspartate （NAA） expression in the hippocampus of rats were investigated. After male Sprague-Dawley （SD） rats were treated intra-gastrically with different doses of MC-LR for 90 d, the locomotor activity, spatial learning and memory function were evaluated in the rats after treatment using open field tests and Morris water maze tests. The results show that MC-LR exposure can lead to impairment of the spatial learning capacity and locomotor activity in rats at the dose of 2. 00 p,g/kg. The levels of NAA in the hippocampus were measured by magnetic resonance spectroscopy （MRI）. A significant decrease of NAA/Cr ratio （ P 〈 0. 05） was observed in the hippocampous. This study indicates that intra-gastrical exposure to low-doses of MC-LR has adverse effects on neuronal behavior and NAA levels in the hippocampous.
基金supported by the National Basic Research Program (973) of China (No. 2014CB932002)the Chinese Academy of Sciences Strategic Priority Research Program (No. XDB14030502)the National Natural Science Foundation of China (Nos. 21177133, U1232144)
文摘Microcystin-LR （MC-LR） is the most abundant and toxic microcystin congener and has been classified as a potential human carcinogen （Group 2B） by the International Agency for Research on Cancer. However, the mechanisms underlying the genotoxic effects of MC-LR during chronic exposure are still poorly understood. In the present study, human-hamster hybrid （AL） cells were exposed to MC-LR for varying lengths of time to investigate the role of nitrogen radicals in MC-LR-induced genotoxicity. The mutagenic potential at the CD59 locus was more than 2-fold higher （p 〈 0.01） in AL ceUs exposed to a cytotoxic concentration （1 μmol/L） of MC-LR for 30 days than in untreated control ceils, which was consistent with the formation of micronucleus. MC-LR caused a dose-dependent increase in nitric oxide （NO） production in treated cells. Moreover, this was blocked by concurrent treatment with the NO synthase inhibitor NC-methyl-L-arginine （L-NMMA）, which suppressed MC-LR- induced mutations as well. The survival of mitochondrial DNA-depleted （pO） AL ceils was markedly decreased by MC-LR treatment compared to that in AL cells, while the CD59 mutant fraction was unaltered. These results provided clear evidence that the genotoxicity associated with chronic MC-LR exposure in mammalian cells was mediated by NO and might be considered as a basis for the development of therapeutics that prevent carcinogenesis.
