Delayed effect of liver injury and metabolism of dimethylformamide after high exposures in rats
10.3760/cma.j.issn.1001-9391.2017.06.002
- VernacularTitle: 高剂量二甲基甲酰胺致大鼠肝毒性和代谢的延迟作用
- Author:
Zhijun WU
1
;
Mingyue GUAN
;
Min ZHENG
;
Man ZHANG
;
Wenjin ZHAO
;
Lijun SHAO
;
Yongchao ZHAI
;
Yuling ZHU
;
Juan CHENG
Author Information
1. The Toxicology Laboratory of National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China
- Publication Type:Journal Article
- Keywords:
Rats;
Dimethylformamide;
Hemoglobin-adduct (NMHb);
Liver;
Delayed
- From:
Chinese Journal of Industrial Hygiene and Occupational Diseases
2017;35(6):402-407
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the delayed effect of liver injury and metabolism of dimethylformamide (DMF) after high exposures in rats.
Methods:A total of 12 rats were randomly divided into four groups and 3 rats were in each group. Rats in 1d DMF+2 d delayed group were dosed for 1 day and rested for 2 days, and sacrificed at the 4th day. Rats in 3 d DMF group were dosed for 3 days and sacrificed at the 4th day. Rats in 3 d DMF+3 d delayed group were dosed for 3 days and rested for 3 days, and sacrificed at the 7th day. Rats in control group were administrated with water for 3 days, sacrificed at the 7th day. The administrated dose was 1 000 mg/kg (body weight·d) DMF by oral. The daily observation and body weight were recorded during the study period. After the experiment, the blood biochemistry, including alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , lactic dehydrogenase (LDH) , alkaline phosphatase (ALP) , total bilirubin (TBIL) etc. were detected. Liver weight, kidney weight, liver/body ratio, kidney/body ratio and pathologic examination of liver and kidney were investigated. The concentrations of hemoglobin-adduct (NMHb) were detected.
Results:During the period of 1~3 d, body weight growth rate of rats in each treated group had no significant difference with control rats. In the 4~6 th day of the period, rats in group 3 became thinner than before, and the body weight was negative growth (-4.22±3.29 g/d) and significant lower than that of control rats (10.33±3.21 g/d, F=30.07, P<0.05) . AST and LDH levels of 3 d DMF group were significant higher than control group (P<0.05) . Liver/body ratio in 3 d DMF+3 d delayed group were significant higher than control group (P<0.05) . The gross inspection showed 1 rat and 3 rats were observed liver injury in 3 d DMF group and 3 d DMF+3 d delayed group, respectively. Histopathological lesions of 1d DMF+2 d delayed group, 3 d DMF group and 3 d DMF+3 d delayed group were mainly spotty necrosis, focal necrosis and large necrosis of liver cells, respectively. Only NMHb level of control group was undetectable. NMHb levels in 3 d DMF+3 d delayed group were significantly higher than 3 d DMF group (F=135.46, P<0.05) .
Conclusion:The DMF-induced liver injury and DMF metabolism may be delayed after high DMF exposures in rats.
