Protective effect of CP-25 on methotrexate-induced liver injury in rats and its molecular mechanism
10.19405/j.cnki.issn1000-1492.2023.04.026
- Author:
Zhengkun Xu
1
;
Qianlei Wang
1
;
Chun Wang
1
;
Wei Wei
1
Author Information
1. Institute of Clinical Pharmacology，Anhui Medical University，Key Laboratory of Anti-infiammatory and Immune Medicine，Ministry of Education，Anhui Collaborative Innovation Center of Anti-inflammatory and Immuno Drugs，Hefei 230032
- Publication Type:Journal Article
- Keywords:
total glucosides of paeony;
CP-25;
methotrexate;
hepatotoxicity;
apoptosis
- From:
Acta Universitatis Medicinalis Anhui
2023;58(4):676-682
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of Paeoniflorin-6 '-o-benzene sulfonate ( CP-25) on methotrexate (MTX) -induced liver injury in rats．
Methods:40 SD rats were randomly divided into normal group，model group，CP-25 treatment group，CP-25 prevention group and resveratrol prevention group．A rat model of liver injury was established by single intraperitoneal injection of MTX (20 mg / kg) ，the levels of serum alanine aminotransferase (ALT) ，aspartate aminotransferase ( AST) ，superoxide dismutase ( SOD) ，glutathione ( GSH) and malondialdehyde (MDA) were determined by ELISA，the levels of interleukin-1 β (IL-1 β) ，interleukin-6 (IL-6) ， tumor necrosis factor-α (TNF-α) ，B-lymphocyte tumor-2 (Bcl-2) ，Bcl-2-associated X (Bax) ，cytochrome C ( Cyt- C) ，cleaved cysteinyl aspartate specific proteinase8 ( cleaved-cas8 ) ，cleaved cysteinyl aspartate specific proteinase 9 (cleaved-cas9) and reduced nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) containing cysteine were assessed by Western blot.
Results:Compared with the normal group，the levels of ALT and AST in MTX-induced liver injury model rats increased (F = 70. 23，P＜0. 01 ; F = 11. 09，P＜0. 05) ，and the liver histopathology showed extensive inflammatory cell infiltration，hepatic lobular structure disorder and hepatocyte swelling. Compared with MTX model group，the levels of ALT and AST in CP-25 prevention group and treatment group were lower (F = 62. 32，86. 86，P＜0. 01 ; F = 16. 35，7. 14，P ＜0. 01 ) ，and the pathological score of liver tissue was lower (F = 18. 33，P＜0. 01 ; F = 15. 47，P＜0. 05) ．Further studies showed that compared with MTX model group， both CP-25 prevention group and treatment group could significantly down-regulate the expression of pro-apoptotic proteins Bax(F = 21. 37，P＜0. 01 ; F = 19. 35，P＜0. 05) ，Cyt-C (FCP-25 prevention group = 7. 21，P＜0. 01) ，cleavedcas8 (FCP-25 prevention group = 12. 32，P＜0. 05) and cleaved-cas9(F = 8. 41，P＜0. 01 ; F = 6. 91，P＜0. 05) ，and upregulate the expression of anti-apoptotic protein Bcl-2 (F = 13. 11，P＜0. 01 ; F = 9. 93，P＜0. 05) . At the same time，compared with MTX model group，CP-25 prevention group and treatment group decreased the levels of IL- 1 β , IL-6 and TNF-α(FCP-25 prevention group = 160. 7，46. 55，28. 89，P＜0. 01) ; FCP-25 treatment group = 127. 4，53. 70，26. 46， P ＜ 0. 01 ) ，down-regulated the levels of MDA and NOX4 ( FCP-25 prevention group = 31. 71，38. 45 ，P ＜ 0. 01 ; FCP-25 treatment group = 27. 89，31. 27，P＜0. 01) ，and up-regulated the level of GSH ( F = 39. 65，29. 04，P ＜0. 01) .
Conclusion:CP-25 has a good therapeutic and protective effect on hepatotoxicity induced by MTX，and this effect may be related to its inhibition of oxidative stress，inflammatory response，and reduction of apoptosis in liver tissue.
- Full text:2024072720064442071CP-25对甲氨蝶呤诱导大...损伤的保护作用及其分子机制_许正坤.pdf
