[Effects of reduced glutathione on contents of hydroxyproline and oxidation stress reaction in kidney of unilateral ureteral obstruction in rat].
OBJECTIVE
To explore therapeutic effect of glutathione (GSH) on unilateral ureteral obstruction (UUO) induced renal interstitial fibrosis and its mechanism in rat.


METHODS
Thirty-six adult healthy Wistar rats were randomly divided into 3 groups (each n=12): sham operation group, UUO group and GSH group. Rats in UUO group and GSH group underwent left unilateral ureteral ligation as described previously. Rats in sham group had their ureters manipulated but not ligated. In GSH group, GSH was injected intraperitoneally (100 mg.kg(-1).d(-1)) in different doses based on the animal's body weight, one day before UUO and then for consecutive 10 days after UUO. Meantime, same volume of physiological saline was given in sham operation and UUO groups as GSH group. Animals were sacrificed at 10 days after surgery. The pathological changes in obstructed kidney tissue were observed with hematoxylin and eosin (HE) and Masson stains. The contents of hydroxyproline (Hyp) and total anti-oxygen capability (T-AOC) were measured by chemical colorimetry method, the activity of total superoxide dismutase (T-SOD) was assayed by a modified xanthine/xanthine oxidase method, and the content of malondialdehyde (MDA) was determined by thiobarbituric acid method.


RESULTS
Ten days after UUO, swelling and atrophy in renal parenchyma of obstructed kidneys were clearly observed. Fibrous material and monocyte infiltration were increased in the interstitial space. Furthermore, thickening of interstitial space of the tubular basement membrane and widening of the interstitial space of the renal cortex were noted. Hypertrophy or atrophy of juxtaglomerular tubules were also observed. There were cellular or albumin casts in a part of tubules. Interstitial fibrosis was observed in obstructed kidneys 10 days after UUO. The data indicated that ureteral obstruction significantly increased the contents of Hyp and MDA, but decreased the content of T-AOC and T-SOD activity, as compared with sham operation group [Hyp: (0.524+/-0.132) microg/mg, T-AOC: (1.48+/-0.21) U/mg, T-SOD: (12.77+/-0.76) U/mg, MDA: (2.65+/-0.32) nmol/mg, all P<0.01]. Compared with UUO group, pathological changes were milder and the contents of Hyp [(1.598+/- 0.252) microg/mg vs. (1.027+/-0.196) microg/mg, P<0.05] and MDA [(4.58+/-0.59) nmol/mg vs. (3.26+/- 0.34) nmol/mg, P<0.05] were significantly decreased in kidney of GSH group, meanwhile the content of T-AOC was increased [(0.67+/-0.19) U/mg vs. (0.94+/-0.17) U/mg, P<0.05], but the content of T-SOD did not show any change [(9.39+/-0.87) U/mg vs. (9.41+/-0.93) U/mg, P>0.05].


CONCLUSIONS
Reduced glutathione treatment attenuates UUO-induced renal interstitial fibrosis via decreasing content of Hyp in UUO kidney and preventing oxidation stress injury.
Na
Yu
Y
Department of Nephrology, the Fourth Hospital, Jilin University, Changchun, Jilin, China.
Zhang
Xiao-xuan
XX
Zhang
Xiao-dong
XD
Yuan
Hong-ping
HP
Hu
Xiu-li
XL
Zheng
Wei
W
Li
Gen
G
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009400:Nephrosclerosis / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005978:Glutathione; D006909:Hydroxyproline