Repairing effects of reduced glutathione and polyene phosphatidyl choline on liver injury evoked by cyclophosphamide in mice
10.3760/cma.j.issn.1008-5734.2014.06.006
- VernacularTitle:还原型谷胱甘肽与多烯磷脂酰胆碱对环磷酰胺诱导小鼠肝损伤的修复作用
- Author:
Xiangju SUN
1
;
Yubo WU
1
;
Aihua JIANG
1
;
Na XU
1
;
Jing LIANG
1
;
Yumeng WU
1
Author Information
1. 150010,哈尔滨医科大学附属第四医院药剂科
- Publication Type:Journal Article
- Keywords:
Cyclophosphamide;
Glutathione;
Phosphatidylcholines;
Drug-induced liver injury
- From:
Adverse Drug Reactions Journal
2014;(6):345-349
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze and compare the prothetic effects of reduced glutathione and polyene phosphatidyl choline on liver injury evoked by cyclophosphamide in mice. Methods Forty Kunming mice were divided into the liver injury model group,the reduced glutathione group,the polyene phosphatidyl choline group,and the control group by simple random sampling. Each group comprised 10 mice. The mice in the fornamed 3 groups received intraperitoneal injection of cyclophosphamide(100 mg ·kg-1 ·d-1 )to evoke the liver injury on day 1 to 4 of the experiment and 0. 9% sodium chloride solution 0. 2 ml,reduced glutathione 180 mg· kg-1 · d-1 ,and polyene phosphatidyl choline 90 mg·kg-1 ·d-1 were given respectively in the 3 groups on day 5 to 14 of the experiment. The mice in the control group received intraperitoneal injection of same volume of 0. 9% sodium chloride solution on day 1 to 14 of experiment. The body weight of mice in the 4 groups were measured on the first day before intraperitoneal injection of cyclophosphamide and the fifteenth day of the experiment. The mice in the 4 groups were executed on the fifteenth day of the experiment. The blood samples were taken from eye pit before the mice were killed and the serum total bilirubin and glutathione levels were measured. Their liver tissue were taken and weighed, and the liver coefficient were calculated. The liver tissue were taken and the activities of alanine aminotransferase( ALT),aspartate aminotransferase( AST),superoxide dismutase( SOD),catalase (CAT)and the level of malonaldehyde( MDA)in the liver tissue were measured. The morphological changes in the liver tissue in the 4 groups were observed. Results On day 15 of experi-ment,the body weights in mice in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group were lower significantly than those in the control group(P < 0. 01 or P < 0. 05). The body weights in mice in the reduced glutathione group were higher than those in the liver injury model group(P <0. 05). The liver coefficient in mice in the liver injury model group(5. 74% ± 0. 11% )was higher than that in the control group(4. 68% ± 0. 37% )and the reduced glutathione group(4. 81% ± 0. 19% )(all P <0. 01). The liver coefficient in mice in the polyene phosphatidyl choline group(5. 25% ± 0. 35% )was higher than that in the control group(P < 0. 05). The levels of serum total bilirubin in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group[(129. 8 ± 1. 9), (110. 9 ±1. 3),and(125. 7 ±2. 6)μmol/ L]were higher than those in the control group[(100. 8 ± 3. 0)μmol/ L](all P < 0. 01). The level of serum total bilirubin in mice in the reduced glutathione group was lower than that in the liver injury model group(P < 0. 01). The levels of serum glutathione in mice in the liver injury model group and the polyene phosphatidyl choline group[(50. 5 ± 1. 9)and(55. 9 ± 2. 4)g/ L] were lower than those in the control group and the reduced glutathione group[(73. 8 ± 4. 3)and(71. 3 ± 3. 7)g/ L](all P < 0. 01). The activities of AST,ALT,SOD,and CAT in the liver tissue in mice in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group were lower than those in the control group[(144. 5 ± 7. 9),(223. 1 ± 15. 1),(173. 9 ± 5. 3)U/ mg vs.(332. 6 ± 7. 3)U/ mg],[(50. 5 ± 4. 0),(108. 0 ± 8. 0),(62. 3 ± 2. 0)U/ mg vs.(139. 6 ± 7. 0)U/ mg],[(99. 0 ± 9. 7),(165. 0 ± 114. 6),(115. 6 ± 7. 3)U/ mg vs. (207. 6 ± 8. 3)U/ mg],[(35. 4 ± 1. 0),(39. 3 ± 1. 1),(36. 3 ± 1. 2)U/ mg vs.(42. 5 ± 2. 3)U/ mg](all P < 0. 01). The MDA levels in the liver injury model group,the reduced glutathione group,and the polyene phosphatidyl choline group were higher than those in the control group[(23. 4 ± 2. 6),(16. 3 ± 1. 5),(20. 2 ± 1. 9)nmol/ mg vs.(10. 2 ± 2. 2)nmol/mg](all P < 0. 01). But the levels of above-mentioned four enzymes in the reduced glutathione group were higher than those in the polyene phosphatidyl choline group and the liver injury model group(P < 0. 01 or P< 0. 05),the levels of MDA were lower than those in the polyene phosphatidyl choline and the liver injury model groups(all P < 0. 05). There were many necrotic foci and inflammatory corpuscles in hepatic tissue in mice in the liver injury model group,the structure of hepatocyte was inordinate. The structure of most hepatocytes in the reduced glutathione group was normal,only few necrotic foci were seen. Part of the hepatocytes in the polyene phosphatidyl choline group showed gap increase,swelling,and a few necrotic foci. Conclusions Reduced glutathione has significant repairing effects on liver injury in mice evoked by cyclophosphamide. Polyene phosphatidyl choline can only increase the ALT activity in the model of liver injury evoked by cyclophosphamide in mice.
