ABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between renal tubular cells transdifferentiation and chronic renal interstitial fibrosis induced by Fangchi Extract in rat.</p><p><b>METHOD</b>The chronic renal interstitial fibrosis rat model was made by giving Radix Aristolochiae Fangchi extract (RAFE) and aristolichic acid (AA) respectively to rats through infusing stomach about 22 weeks discontinuously. Through immunnal histochemistry methods, investigating the expression of symbol proteins: Cytokine( CK) , alpha-Smooth muscle actin ( alpha-SMA) and Vimentin, and also the important fibrosis inducing factor-Transforming growth factor-beta (TGF-beta1 )on renal tubular cells.</p><p><b>RESULT</b>In RAFE and AA Groups, the expression of CK on renal tubular cells is declined comparing with the Control Group, and the enhanced expression of alpha-SMA and Vimentin can be observed on tubular cells. The expression of TGF-beta1 on renal tubular cells stronglhy increased, too.</p><p><b>CONCLUSION</b>Part of the renal tubular cells was transdifferentiated into myofibroblasts. Renal tubular cells may participate the occurance of chronic renal interstitial fibrosis, TGF-beta1 may accelerate the transdifferentiation of tubular cells.</p>
Subject(s)
Animals , Female , Male , Rats , Actins , Metabolism , Aristolochia , Chemistry , Aristolochic Acids , Toxicity , Cell Transdifferentiation , Cytokines , Metabolism , Drugs, Chinese Herbal , Toxicity , Epithelial Cells , Metabolism , Pathology , Fibrosis , Kidney Diseases , Metabolism , Kidney Tubules , Metabolism , Pathology , Plant Extracts , Therapeutic Uses , Plant Roots , Chemistry , Plants, Medicinal , Chemistry , Random Allocation , Rats, Sprague-Dawley , Transforming Growth Factor beta1 , Metabolism , Vimentin , MetabolismABSTRACT
<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>
Subject(s)
Animals , Female , Male , Mice , Rats , Acetylglucosaminidase , Urine , Aristolochia , Chemistry , Toxicity , Aristolochic Acids , Toxicity , Blood Urea Nitrogen , Body Weight , Dose-Response Relationship, Drug , Drugs, Chinese Herbal , Toxicity , Fibrosis , Kidney Tubules , Pathology , Plant Roots , Chemistry , Toxicity , Plants, Medicinal , Chemistry , Toxicity , Proteinuria , Random Allocation , Rats, Sprague-DawleyABSTRACT
Higenamine (HG) is a potent cardioactive benzylisoquinoline alkaloid isolated from Aconiti tuber which has long been used as a cardiotonic in traditional Chinese medicine. HG exerts various effects on the cardio-circulatory system inotropic and chronotropic in isolated rat atria. It also relaxes isolated rat aorta. It inhibits epinephrine, ADP or collagen-induced platelet aggregation in platelet rich plasma. HG inhibits LPS-induced nitrate accumulation and the expression of iNOS mRNA in RAW 264.7 cells. HG lowers blood pressure in rats and increases the recovery rates in acute thrombosis model of mice, and lower the weight of thrombus formed in the arterio-venous shunt model of rats. Higenamine also has ameliorative effects in the LPS-induced DIC model.