[Experimental study of chronic renal tubular-interstitial injury induced by radix aristolochiae fangchi extract in rats].
OBJECTIVE
To observe the acute and chronic renal toxicity induced by Radix Aristolochiae Fangchi Extract (RAFE) in different doses in rats.


METHODS
The conventional method of acute toxicity was used. RAFE at the dose of 25.0 mg x kg(-1) x d(-1), 120.0 mg x kg(-1) x d(-1) and 200.0 mg x kg(-1) x d(-1) and aristolochic acid (AA, 10.0 mg x kg(-1) x d(-1)) were interruptedly administrated to rats for 13 week by gastric tube, and the sample of blood, urine and kidney were collected at 4 week, 8 week and 13 week respectively. The indexes of renal function were measured and the morphology of kidney was observed.


RESULTS
LD50 of RAFE was 36.8 g x kg(-1) (the crude drug) and the 95% confidence limit was 38.8 - 28.9 g x kg(-1). The changes of renal functions were azotemia, massive proteinuria and the increase of urinary NAGase (beta-N-acetylglucosaminidase) in the earlier period of administration with RAFE in rats. Pathological changes of renal tissue were as follows: acute renal tubular necrosis mainly in the boundary of cortex and medulla was observed in the earlier period, and with the elongation of administration, the pathological process of renal interstitial fibrosis observed in the middle and high groups of RAFE and AA group.


CONCLUSIONS
RAFE at middle and high doses administrated by interrupted gavage above 13 week can cause the injury of renal tubular functions in rats. NAGase can be used as one of observation targets in the earlier period of renal injury.
Du
Gui-You
GY
Institute of Chinese Materia Medica, China Academy of Traditional Chinese Medicine, Beijing 100700, China. duguiyou1942@Vip.Sina.com
Zhou
Su-Juan
SJ
Zhao
Yong
Y
Cu
Hai-Feng
HF
Wang
Xiu-Rong
XR
Li
Li
L
Xiao
Yong-Qing
YQ
Cao
Chun-Yun
CY
Zhang
Chun-Ying
CY
Wu
Zi-Lun
ZL
Gao
Shuang-Rong
SR
He
Rong
R
Hui
Lian-Qiang
LQ
Liu
Bao-Yan
BY
D000118:Acetylglucosaminidase / Q000652:urine*; D000818:Animals; D030022:Aristolochia / Q000737:chemistry / Q000633:toxicity*; D034341:Aristolochic Acids / Q000302:isolation & purification / Q000633:toxicity*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D005260:Female; D005355:Fibrosis / Q000139:chemically induced; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D051379:Mice; D018517:Plant Roots / Q000737:chemistry / Q000633:toxicity; D010946:Plants, Medicinal / Q000737:chemistry / Q000633:toxicity; D011507:Proteinuria / Q000139:chemically induced; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D000118:Acetylglucosaminidase