Effect of melatonin on PCB (Aroclor 1254) induced neuronal damage and changes in Cu/Zn superoxide dismutase and glutathione peroxidase-4 mRNA expression in cerebral cortex, cerebellum and hippocampus of adult rats.
Polychlorinated biphenyls (PCBs) are one of the environmental toxicants and neurotoxic compounds which induce the production of free radicals leading to oxidative stress. Free radicals represent a class of biologically generated species that pose a potential threat to neuronal survival. Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase-4 (GPx-4) are the key cellular antioxidant enzymes by which neurons and other cells detoxify free radicals and protect themselves from damage. Melatonin, an indoleamine plays an important role in neurodegenerative diseases as an antioxidant and neuroprotector. The aim was to carry out to investigate the effect of melatonin on PCB (Aroclor 1254) induced changes in histomorphology and Cu/Zn SOD, GPx-4 mRNA expression in selected brain regions of adult rats. Group I: rats intraperitoneally (i.p.) administered with corn oil (vehicle) for 30 days. Group II: rats injected (i.p.) with Aroclor 1254 (PCB) at 2mg/kgbw/day for 30 days. Groups III and IV: rats (i.p.) received melatonin (5 or 10mg/kgbw/day) simultaneously with PCB for 30 days. Groups V and VI: rats (i.p.) received melatonin (5 or 10mg/kgbw/day) alone for 30 days. After 30 days, rats were sacrificed and the brain regions were dissected to cerebral cortex, cerebellum and hippocampus. Activities of enzymatic antioxidants such as total SOD, Cu/Zn SOD, Mn SOD, glutathione peroxidase (GPx) were estimated. mRNA expressions of Cu/Zn SOD and GPx-4 were quantified by reverse transcriptase polymerase chain reaction (RT-PCR) method. Histological study was also observed. Specific activities of all antioxidant enzymes and mRNA expression of Cu/Zn SOD and GPx-4 were decreased in brain regions of PCB exposed animals. Neuronal damages were observed in all the brain regions. Exogenous melatonin supplementation retrieved all the parameters. These results suggest that melatonin protects PCB-induced oxidative stress and prevents neuronal damage in brain regions.
Venkataraman
Prabhu
P
Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Chennai, India.
Selvakumar
Kandaswamy
K
Krishnamoorthy
Gunasekaran
G
Muthusami
Sridhar
S
Rameshkumar
Radhakrishnan
R
Prakash
Seepan
S
Arunakaran
Jagadeesan
J
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D057075:Enzyme Assays; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D020111:Chlorodiphenyl (54% Chlorine); D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; C523860:glutathione peroxidase 4, rat; D013482:Superoxide Dismutase; D008550:Melatonin