Effect of fasudil of on rat cardiomyocytes acutely exposed to omethoate.
- Author:
Xian-liang YAN
1
;
Wei HUANG
;
Jiang-hua CHENG
;
Hou-qing WANG
;
Tie XU
Author Information
- Publication Type:Journal Article
- MeSH: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; analogs & derivatives; pharmacology; Animals; Cells, Cultured; Dimethoate; analogs & derivatives; toxicity; Male; Myocytes, Cardiac; drug effects; metabolism; Pesticides; poisoning; Proto-Oncogene Proteins c-bcl-2; metabolism; Rats; Rats, Sprague-Dawley; bcl-2-Associated X Protein; metabolism
- From: Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(9):656-660
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of fasudil on in vitro cultured cardiomyocytes (CMs) exposed to omethoate and its possible mechanism.
METHODSCardiomyocytes were isolated from male SD rats and were then cultured in DMEM conventionally. The CMs were divided into different groups based on the doses of omethoate and fasudil in culture media. After 3, 6, 12, and 24 h of culture, the survival rate of CMs in each group was measured, the CMs in the medium-dose omethoate and medium-dose fasudil groups were subject to shortening amplitude measurement , and the content of lactate dehydrogenase (LDH) in culture media and expression of Bcl-2 and Bax in CMs were measured.
RESULTSCompared with the normal control group, each omethoate group showed significantly lower survival rate of CMs, which was negatively correlated with the dose of omethoate (P < 0.01). Compared with the normal control group, the medium-dose omethoate and medium-dose fasudil groups showed significantly decreased shortening amplitudes of CMs at all time points (P < 0.01), and the shortening amplitudes of CMs were significantly higher in the medium-dose fasudil group than in the medium-dose omethoate group after 12 h and 24 h of culture (P < 0.01). The LDH level was significantly higher in the medium-dose omethoate and medium-dose fasudil groups than in the normal control group, and the medium-dose fasudil group showed significantly lower LDH level than the medium-dose omethoate group (P < 0.01). Compared with those in the normal control group, the Bcl-2 expression in the medium-dose omethoate and medium-dose fasudil groups was decreased significantly, and the Bax expression in the medium-dose omethoate group was increased significantly (P < 0.01). Compared with the medium-dose omethoate group, the medium-dose fasudil group had significantly increased Bcl-2 expression and significantly decreased Bax expression (P < 0.01).
CONCLUSIONFasudil can inhibit the abnormal expression of apoptosis regulatory proteins (Bcl-2 and Bax) induced by omethoate, which might be one of the factors that reduce the toxic effect of omethoate on CMs.
