Inducible nitric oxide synthase is involved in neuronal death induced by trimethyltin in the rat hippocampus |
Sukwon Jang1, Sungyoung Choi1, Changnam Park1, Meejung Ahn2, Taekyun Shin1, Seungjoon Kim3 |
1College of Veterinary Medicine and Veterinary Medical Research Institute, Jeju National University 2Department of Anatomy, School of Medicine, Jeju National University 3College of Veterinary Medicine, Kyungpook National University |
Trimethyltin에 의한 랫드 해마의 신경세포 사멸과 iNOS의 연관성 |
장석원1, 최성영1, 박창남1, 안미정2, 신태균1, 김승준3 |
1제주대학교 수의과대학 2제주대학교 의학전문대학원 3경북대학교 수의과대학 |
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Abstract |
Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT. |
Key Words:
aminoguanidine, hippocampus, iNOS, trimethyltin |
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