lmprovement effect and anti-oxidative stress mechanism of rosiglitazone against cisplatin-induced nephropathy in rats
10.3867/j.issn.1000-3002.2014.04.009
- VernacularTitle:罗格列酮对顺铂所致肾损伤大鼠肾功能的改善作用及其抗氧化应激作用机制
- Author:
Ling ZHANG
;
Hua FAN
- Publication Type:Journal Article
- Keywords:
rosigIitazone;
cispIatin;
nephropathy;
oxidative stress
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(4):525-530
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTlVE To investigate the improvement effect of rosigIitazone(ROm)against cis-pIatin(DDP)-induced nephropathy in rats and its mechanim of resistance to oxidative stress. METHODS Invitro:the survivaI rate of HEK293 ceIIs was measured with mTT assay incubated with DDP 0.4 -100 μmoI·L-1 aIone or with DDP 25 μmoI·L-1 and ROm 0.01-1000 μmoI·L-1 for 48 h. Then the content of maIondiaIdehyde(mDA)and the activity of gIutathione(GSH)in HEK293 ceIIs co-incubated with DDP 25 μmoI·L-1 and ROm 100 μmoI·L-1 were assayed using chromatometry. In vivo:sixty maIe SD rats were randomIy divided into normaI controI group,modeI group(DDP 5 mg·kg-1 )and modeI+ROm 5,10 and 20 mg·kg-1 groups. The modeI of DDP-induced nephropathy was estabIished by taiI vein injection of DDP 5 mg·kg-1 ,once a week,for 3 times. After the first injection,the rats in modeI+ROm 5,10 and 20 mg·kg-1 groups were ig given ROm 5,10 and 20 mg·kg-1 ,once a week,for 8 weeks. The bIood urea nitrogen(BUN)and creatinine(Cr)were assessed with an automatic biochemicaI anaIyzer. Nitric oxide(NO)and mDA content,GSH and superoxide dismutase( SOD)activities in the kidney tissue were determined using chromatometry and histopathoIogicaI changes in renaI tissues were detected by hematoxyIin-eosin staining. RESULTS In vitro:IC50 of DDP to HEK293 ceII survivaI for 48 h was 21.0 μmoI·L-1 . Co-incubation with ROm 1-1000 μmoI·L-1 and DDP 25 μmoI·L-1 for 48 h couId signifi-cantIy increase the totaI ceII survivaI rate compared with DDP 25 μmoI·L-1 group(P﹤0.05,P﹤0.01), whiIe co-incubation with ROm 100 μmoI·L-1 and DDP 25 μmoI·L-1 for 48 h couId significantIy decrease the IeveI of mDA(P﹤0.01)and increase GSH activity(P﹤0.01),respectiveIy. In vivo:compared with normaI group,serum BUN and Cr content in modeI group were significantIy increased(P﹤0.01),renaI tissue GSH and SOD activities decreased(P﹤0.01),renaI tissue mDA content increased(P﹤0.01), and renaI tissue NO IeveI and NOS activity aIso decreased significantIy(P﹤0.05). Compared with modeI group,serum BUN content in modeI+ROm 5,10 and 20 mg·kg-1 decreased from(17.0±1.3)mmoI·L-1 to 14.0±4.1,11.2±1.8 and(6.1±1.0)mmoI·L-1(P﹤0.01),serum Cr content in modeI+ROm 10 and 20 mg·kg-1 decreased from(124.6±39.8)mmoI·L-1 to 49.0±5.2 and(47.1±2.9)mmoI·L-1(P﹤0.01), renaI tissue GSH and SOD activities in modeI+ROm 10 and 20 mg·kg-1 group increased significantIy (P﹤0.05,P ﹤ 0. 01),mDA IeveI decreased(P﹤0.05,P ﹤ 0. 01),NO IeveI and NOS activity aIso increased(P﹤0.05,P﹤0.01),and renaI pathoIogicaI tissue damage couId be improved. CONCLUSlON ROm pIays a protective roIe in rat kidney damage caused by DDP,which may be reIated to improving oxidative stress resistance of the kidney.
