ABSTRACT
<p><b>OBJECTIVE</b>Following the former report, we continue to observe the chronic renal tubular-interstitial injury induced by Radix Aristolochiae Fangchi Extract(RAFE) in rats in order to understand whether RAFE in different doses causes the renal tubular-interstitial injury or not.</p><p><b>METHOD</b>RAFE at the dose of 25.0 mg x kg(-1) x d(-1), 120.0 mg 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) d(-1)) was interruptedly administrated by gastric tube for 22 w and 4 w durg withdrawal. Blood, urine and kidney were taken out respectively in 17 w, 22 w and 26 w to measure the indexes of renal function. The morphology of kidney was observed, and Masson staining of kidney were made respectively to compare RAFE groups with AA group.</p><p><b>RESULT</b>Pathological changes of renal tissue forms were as follows: All RAFE groups and AA group could develop the pathological process of renal tubular injury-chronic renal interstitial fibrosis. The pathologic changes of RAFE were similar with AA.</p><p><b>CONCLUSION</b>RAFE at all doses administrated interruptedly by gastric tube above 13 w caused chronic renal tubulo-interstitium fibrosis. The renal injury in functions and tissue forms in rats were similar with AA closely. The results showed that AA was the main toxic composition of RAFE.</p>
Subject(s)
Animals , Female , Male , Rats , Aristolochia , Chemistry , Toxicity , Aristolochic Acids , Toxicity , Blood Urea Nitrogen , Body Weight , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Toxicity , Fibrosis , Blood , Pathology , Kidney Tubules , Pathology , Nephritis, Interstitial , Blood , Pathology , Plant Roots , Chemistry , Toxicity , Plants, Medicinal , Chemistry , Toxicity , Proteinuria , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To observe the acute and chronic renal toxicity induced by Radix Aristolochiae Fangchi Extract (RAFE) in different doses in rats.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>