Protective effect of reduced glutathione on acute renal injury induced by diclofenac in rats and its mechanism
10.3760/cma.j.cn114015-20220622-00553
- VernacularTitle:还原型谷胱甘肽对双氯芬酸所致大鼠急性肾损伤的防护作用及其机制研究
- Author:
Shuifang CHEN
1
;
Hui CHEN
;
Xuemei CHEN
;
Meiling LYU
;
Jiumei SHEN
;
Fengqing JI
Author Information
1. 厦门市中医院药学部，厦门 361009
- Publication Type:Journal Article
- Keywords:
Glutathione;
Diclofenac;
Acute kidney injury;
Oxidative stress;
Inflammatory response
- From:
Adverse Drug Reactions Journal
2023;25(4):223-228
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect of reduced glutathione (GSH) on diclo-fenac-induced acute kidney injury (AKI) in rats and its mechanism.Methods:Thirty-three male 8-week-old specified pathogen-free SD rats were randomly divided into control, model, and GSH groups (11 rats in each group) according to a random number table method. Diclofenac sodium solution (200 mg/kg) was intragastrically administered to rats in the model group and GSH group to establish the AKI model. Thirty minutes later, rats in the GSH group were treated with intragastric administration of GSH solution (500 mg/kg), while rats in the control and model groups were with 0.9% sodium chloride injection of equal volume. After 24 hours of administration, blood sample was collected and kidneys were isolated. Kidney function [blood urea nitrogen (BUN), serum creatinine (Scr)], kidney histopathology, and serum and kidney tissue oxidative stress indicators such as malondialdehyde (MDA), superoxide dismutase (SOD), and the inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin 6 (IL-6) were examined. The results of each examination results among rats of the 3 groups were compared.Results:The BUN and Scr in rats of the model group were significantly higher than those in the control and GSH groups[BUN: (14.34±8.47) mmol/L vs. (7.89±2.20) and (8.46±3.58) mmol/L; Scr: (34.44±6.56) μmol/L vs. (24.77±9.50) and (29.28±4.33) μmol/L, all P<0.05]. Glomerular and tubular morphological changes were observed in both model and GSH rats, but the change in rats of GSH group was less severe than that of the model group. The mean levels of MDA, TNF-α, and IL-6 in both serum and kidney tissue in rats of GSH group were significantly lower than those of the model group[MDA: (9.5±0.2) nmol/ml vs. (10.2±0.6) nmol/ml, (3.6±0.3) nmol/ml vs. (4.0±0.2) nmol/ml; TNF-α: (2.9±2.5) pg/ml vs. (5.4±3.0) pg/ml, (420.9±40.3) pg/ml vs. (470.4±31.3) pg/ml; IL-6: (92.1±34.4) pg/ml vs. (123.9±16.6) pg/ml, (7 547±604) pg/ml vs. (8 047±470) pg/ml, all P<0.05], while the activity of SOD was significantly higher than that in the model group[(102.8±2.8) U/ml vs. (99.7±4.1) U/ml, (387.0±12.7) U/ml vs. (375.9±11.7) U/ml, all P<0.05]. Conclusion:GSH has a protective effect on diclofenac-induced acute kidney injury in rats, and its possible mechanism is to inhibit oxidative stress and inflammatory reactions.
