Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats

Acta Pharmacol Sin. 2000 Dec;21(12):1129-35.

Abstract

Aim: To investigate the long-term functional and morphological changes of the kidney induced by acute intoxication of Aristolochia manshuriensis Kom in rats.

Methods: Experimental model of acute renal injury was established in the Sprague-Dawley rats with oral administration of decoctions of Chinese herb, Aristolochia manshuriensis Kom, at dosages of 50 g.kg-1.d-1 and 30 g.kg-1.d-1 for 7 consecutive days, and 20 g.kg-1.d-1 for 15 consecutive days. Renal function was assayed at months 0 (right after treatment), 1, 3, and 6 of the experiment. Renal histological examination was also performed.

Results: 1) At month 0, the renal functional changes of acute renal injury included azotemia, low molecular weight proteinuria, glycosuria, hypoosmotic urine, and NAG enzymuria. Histopathological changes showed acute tubular necrosis, predominantly at the corticomedullary junction. 2) At months 1 and 3, the renal function of rats of the experiment was gradually restored and histopathologic examination suggested that the tubular lesions gradually recovered. In HE sections, basophilic deposits were observed in the tubular cytoplasm. And interstitial infiltration of inflammatory cells was not prominent. 3) At months 6, renal preneoplastic lesions, renal tumors, and extrarenal tumors occurred in rats. The occurrence of renal preneoplastic lesions at dosages of 50 g.kg-1.d-1, 30 g.kg-1.d-1, and 20 g.kg-1.d-1 were 100.0% at all three doses, renal tumors 42.8%, 25.0%, and 0%, respectively, extrarenal tumors 14.4%, 12.5%, and 12.5%, respectively, and systemic tumors 57.2%, 37.5%, and 12.5%, respectively. The occurrence of basophilic deposits, renal preneoplastic lesions, renal tumors, and extrarenal tumors in normal control group was nil.

Conclusions: 1) Administration of large dosage of Aristolochia manshuriensis Kom induces acute renal failure in rats. 2) The long-term renal function and histopathologic changes of acute renal injury induced by Aristolochia manshuriensis Komrecover spontaneously. 3) Aristolochia manshuriensis Kom has been proved to be oncogenic for the first time.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / pathology
  • Animals
  • Aristolochia / toxicity*
  • Drugs, Chinese Herbal / toxicity*
  • Female
  • Kidney / pathology*
  • Kidney Neoplasms / chemically induced*
  • Kidney Neoplasms / pathology
  • Mesenchymoma / chemically induced
  • Mesenchymoma / pathology
  • Plants, Medicinal / toxicity*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Wilms Tumor / chemically induced
  • Wilms Tumor / pathology

Substances

  • Drugs, Chinese Herbal