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Melatonin Attenuates Oxidative Damage Induced by Acrylamide In Vitro and In Vivo.

Pan X, Zhu L, Lu H, Wang D, Lu Q, Yan H - Oxid Med Cell Longev (2015)

Bottom Line: Results in cells showed that reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after ACR treatment for 24 h.Using MDA generation, glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in rat cerebellum as indicators, MT alleviated ACR-induced lipid peroxidation and depressed antioxidant capacity.Our results suggest that MT effectively prevents oxidative damage induced by ACR.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; Institute for Environmental Medicine, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

ABSTRACT
Acrylamide (ACR) has been classified as a neurotoxic agent in animals and humans. Melatonin (MT) has been shown to be potentially effective in preventing oxidative stress related neurodegenerative disorders. In this study, whether MT exerted a protective effect against ACR-induced oxidative damage was investigated. Results in cells showed that reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after ACR treatment for 24 h. MT preconditioning or cotreatment with ACR reduced ROS and MDA products, whereas the inhibitory effect of MT on oxidant generation was attenuated by blocking the MT receptor. Increased DNA fragmentation caused by ACR was significantly decreased by MT coadministration. In vivo, rats at 40 mg/kg/day ACR by gavage for 12 days showed weight loss and gait abnormality, Purkinje cell nuclear condensation, and DNA damage in rat cerebellum. MT (i.p) cotreatment with ACR not only recovered weight and gait of rats, but also decreased nuclear condensation and DNA damage in rat cerebellum. Using MDA generation, glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in rat cerebellum as indicators, MT alleviated ACR-induced lipid peroxidation and depressed antioxidant capacity. Our results suggest that MT effectively prevents oxidative damage induced by ACR.

No MeSH data available.


Related in: MedlinePlus

Effects of MT on behavior toxicity of rats and morphology of different brain regions. Experimental rats were divided into four groups: control (equal volume saline) group, ACR (40 mg/kg/day) treatment group, MT (5 mg/kg/day, i.p) treatment group, and ACR + MT simultaneously treatment group. Body weight (a) and gait of rats (b) were analyzed after ACR oral administration with or without MT for 0, 3, 6, 9, and 12 days. H&E staining was used to observe morphological alterations of nerve cells, and the photographs were taken under a light microscope (scale bar: 100 μm) (c). The results are expressed as the mean ± SD (n = 8). ∗P < 0.05, ∗∗P < 0.01 versus the vehicle control group, #P < 0.05, ##P < 0.01 versus the ACR treatment group.
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fig2: Effects of MT on behavior toxicity of rats and morphology of different brain regions. Experimental rats were divided into four groups: control (equal volume saline) group, ACR (40 mg/kg/day) treatment group, MT (5 mg/kg/day, i.p) treatment group, and ACR + MT simultaneously treatment group. Body weight (a) and gait of rats (b) were analyzed after ACR oral administration with or without MT for 0, 3, 6, 9, and 12 days. H&E staining was used to observe morphological alterations of nerve cells, and the photographs were taken under a light microscope (scale bar: 100 μm) (c). The results are expressed as the mean ± SD (n = 8). ∗P < 0.05, ∗∗P < 0.01 versus the vehicle control group, #P < 0.05, ##P < 0.01 versus the ACR treatment group.

Mentions: To further confirm the protective effect of MT on behavioral toxicity induced by ACR, ACR poisoning rat models were established. Body weight (Figure 2(a)) and gait (Figure 2(b)) in rats were assessed, and morphological alterations in nerve cells in different brain regions were observed by H&E staining with a light microscope (Figure 2(c)). The body weight of rats at 40 mg/kg/day ACR significantly decreased since the third exposure day. When rats were cotreated with 5 mg/kg/day MT (i.p) and 40 mg/kg/day ACR, the originally reduced weight caused by ACR administration showed some improvement compared with the group treated with ACR only. Similarly, gait score in the ACR group also significantly increased since the third exposure day. However, gait score in the MT intervention group significantly decreased on days 6 and 9 of ACR treatment, compared with the ACR alone group. In addition, immunohistochemical results showed that unclear cellular gradation, concentrated cell nucleus, and decreased neurons were observed in the cortex of ACR exposure, which indicated that ACR caused abnormal lesions in the cortex of rats. However, the effect of ACR on cortex neurons was not lightened by the addition of MT. Meanwhile, the increased piriform bulging neurons and the decreased grain layer neurons were observed in Purkinje cells of cerebellum in the ACR treatment group. When MT was added, the piriform bulging neurons were reduced and karyopyknosis were weakened in Purkinje cells. Therefore, MT relieved dyskinesia, pathological changes, and karyopyknosis induced by ACR in the cerebellum of rats.


Melatonin Attenuates Oxidative Damage Induced by Acrylamide In Vitro and In Vivo.

Pan X, Zhu L, Lu H, Wang D, Lu Q, Yan H - Oxid Med Cell Longev (2015)

Effects of MT on behavior toxicity of rats and morphology of different brain regions. Experimental rats were divided into four groups: control (equal volume saline) group, ACR (40 mg/kg/day) treatment group, MT (5 mg/kg/day, i.p) treatment group, and ACR + MT simultaneously treatment group. Body weight (a) and gait of rats (b) were analyzed after ACR oral administration with or without MT for 0, 3, 6, 9, and 12 days. H&E staining was used to observe morphological alterations of nerve cells, and the photographs were taken under a light microscope (scale bar: 100 μm) (c). The results are expressed as the mean ± SD (n = 8). ∗P < 0.05, ∗∗P < 0.01 versus the vehicle control group, #P < 0.05, ##P < 0.01 versus the ACR treatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491391&req=5

fig2: Effects of MT on behavior toxicity of rats and morphology of different brain regions. Experimental rats were divided into four groups: control (equal volume saline) group, ACR (40 mg/kg/day) treatment group, MT (5 mg/kg/day, i.p) treatment group, and ACR + MT simultaneously treatment group. Body weight (a) and gait of rats (b) were analyzed after ACR oral administration with or without MT for 0, 3, 6, 9, and 12 days. H&E staining was used to observe morphological alterations of nerve cells, and the photographs were taken under a light microscope (scale bar: 100 μm) (c). The results are expressed as the mean ± SD (n = 8). ∗P < 0.05, ∗∗P < 0.01 versus the vehicle control group, #P < 0.05, ##P < 0.01 versus the ACR treatment group.
Mentions: To further confirm the protective effect of MT on behavioral toxicity induced by ACR, ACR poisoning rat models were established. Body weight (Figure 2(a)) and gait (Figure 2(b)) in rats were assessed, and morphological alterations in nerve cells in different brain regions were observed by H&E staining with a light microscope (Figure 2(c)). The body weight of rats at 40 mg/kg/day ACR significantly decreased since the third exposure day. When rats were cotreated with 5 mg/kg/day MT (i.p) and 40 mg/kg/day ACR, the originally reduced weight caused by ACR administration showed some improvement compared with the group treated with ACR only. Similarly, gait score in the ACR group also significantly increased since the third exposure day. However, gait score in the MT intervention group significantly decreased on days 6 and 9 of ACR treatment, compared with the ACR alone group. In addition, immunohistochemical results showed that unclear cellular gradation, concentrated cell nucleus, and decreased neurons were observed in the cortex of ACR exposure, which indicated that ACR caused abnormal lesions in the cortex of rats. However, the effect of ACR on cortex neurons was not lightened by the addition of MT. Meanwhile, the increased piriform bulging neurons and the decreased grain layer neurons were observed in Purkinje cells of cerebellum in the ACR treatment group. When MT was added, the piriform bulging neurons were reduced and karyopyknosis were weakened in Purkinje cells. Therefore, MT relieved dyskinesia, pathological changes, and karyopyknosis induced by ACR in the cerebellum of rats.

Bottom Line: Results in cells showed that reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after ACR treatment for 24 h.Using MDA generation, glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in rat cerebellum as indicators, MT alleviated ACR-induced lipid peroxidation and depressed antioxidant capacity.Our results suggest that MT effectively prevents oxidative damage induced by ACR.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Toxicology, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; Institute for Environmental Medicine, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

ABSTRACT
Acrylamide (ACR) has been classified as a neurotoxic agent in animals and humans. Melatonin (MT) has been shown to be potentially effective in preventing oxidative stress related neurodegenerative disorders. In this study, whether MT exerted a protective effect against ACR-induced oxidative damage was investigated. Results in cells showed that reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after ACR treatment for 24 h. MT preconditioning or cotreatment with ACR reduced ROS and MDA products, whereas the inhibitory effect of MT on oxidant generation was attenuated by blocking the MT receptor. Increased DNA fragmentation caused by ACR was significantly decreased by MT coadministration. In vivo, rats at 40 mg/kg/day ACR by gavage for 12 days showed weight loss and gait abnormality, Purkinje cell nuclear condensation, and DNA damage in rat cerebellum. MT (i.p) cotreatment with ACR not only recovered weight and gait of rats, but also decreased nuclear condensation and DNA damage in rat cerebellum. Using MDA generation, glutathione (GSH) level, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities in rat cerebellum as indicators, MT alleviated ACR-induced lipid peroxidation and depressed antioxidant capacity. Our results suggest that MT effectively prevents oxidative damage induced by ACR.

No MeSH data available.


Related in: MedlinePlus