Antagonistic effect of calpain inhibitor MDL 28170 on acute methylmercury neurotoxicity in rats
10.3867/j.issn.1000-3002.2010.01.008
- VernacularTitle:钙蛋白酶抑制剂Ⅲ MDL 28170对大鼠甲基汞急性神经毒性的拮抗作用
- Author:
Jian ZHANG
;
Min ZHANG
- Publication Type:Journal Article
- Keywords:
MDL 28170;
protease inhibitors;
methylmercury;
neurons;
apoptosis
- From:
Chinese Journal of Pharmacology and Toxicology
2010;24(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the antagonistic effect of calpain inhibitor Ⅲ MDL 28170 on acute methylmercury (MeHg) neurotoxicity. METHODS The rats were randomly divided into MDL 28170 (50 mg·kg~(-1),ip) control group, MeHg (10 mg·kg~(-1),ig), and MeHg (10 mg·kg~(-1),ig)+MDL 28170 (50 mg·kg~(-1), ip) group. The escape latencies were observed by Morris water maze test. The neurons of positive μ-calpain were determined by immunohistochemical method, the expression of μ-calpain was analyzed by Western blotting, apoptotic neurons were observed by TUNEL method, and microtubule-associated protein 2 (MAP2) expression was detected in neuron by immunohistochemical method. RESULTS MeHg was ig given for 3-7 d, the initial signs of behavioral changes developed in MeHg group, the escape latencies were lengthened in Morris water maze test (P<0.01). The expression and activity of μ-calpain elevated obviously in parietal cerebral neurons(P<0.01), neuronal apoptosis was markedly increased(P<0.01), and the decomposition of MAP2 was reduced in cortical neurons obviously. And the above changes were suppressed obviously by treatment of MDL 28170. CONCLUSION μ-Calpain may correlate with neuronal apoptosis induced by MeHg, MDL 28170 markedly reduces neuronal apoptosis, which might act as therapeutical method for MeHg poison.
