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Vitamin E mitigates the decremental effect of paraquat on Substantia Nigra neurons
Author(s) -
Fahim Mohamed Abdelmonem,
Nemmar Abderrahim,
Shehab Safa,
Dhanasekaran Subramanian,
Yasin Javed,
Shafiullah Mohamed,
Hasan Mohamed
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.742.1
Subject(s) - substantia nigra , pars compacta , tyrosine hydroxylase , dopaminergic , dopamine , endocrinology , medicine , paraquat , vitamin c , chemistry , biochemistry
Background Paraquat (PAR) is a toxic chemical that is widely used as an herbicide in developing countries and has been described as a major suicide agent. Patients with acute PQ poisoning show damage to the lungs, liver, and kidneys, and some also show symptoms of central nervous system toxicity. The hypothesis tested here is that PAR decreased dopamine producing neurons which may be attributed to oxidative stress and therefore the possible effect of vitamin E as an antioxidants to mitigate such loss would be explored. Methodology Forty adult male Wistar rats were divided into 4 groups. Animals received daily intraperitoneal injections for 3 weeks as follows; Group 1 received PAR (10 mg/kg), Group 2 served as controls and received saline, Group 3 received vitamin E (100mg/kg) and Group 4 received PAR (10mg/kg) and vitamin E (100mg/kg). Dopamine concentrations in the ventral mesencephalon were measured by high performance liquid chromatography and the number of dopaminergic neurons in substantia nigra pars compacta was estimated by tyrosine hydroxylase immunohistochemistry. Principal Findings The number of tyrosine hydroxylase positive neurons was significantly less in the substantia nigra pars compacta and nigral dopamine level was significantly reduced in PQ treated animals (20.4±3.4 pg/mg) when compared with control animals (55.0±2.4 pg/mg wet tissue). Daily treatment of PQ for three weeks induces selective dopaminergic neuronal loss in the substantia niagra (32.6±2.1 compared with control animals 47.5±4.2 and vitamin E treated animals 46.0±3.3). PAR caused a significant increase in superoxide dismutase (SOD) and catalase (CAT) levels in brain tissue, indicating that PAR could inititate adaptive responses that counterbalance the potatially damaging activity of oxygen radicals induced by PAR exposure. Adininistration of vitamin E in combination with PAR alleviated most of these adverse effects induced by PAR. SOD and CAT activities were increased in a comparable way in both PAR and vitamin E plus PAR groups. Conclusions It can be concluded that dopaminergic neurons in substantia niagra is compromised in rats exposed to PAR and that the abnormalities are ameliorated by vitamin E treatment.