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      Effect of colchicine on chronic ciclosporin nephrotoxicity in Sprague-Dawley rats.

      Nephron. Physiology
      Animals, Body Weight, drug effects, Colchicine, therapeutic use, Cyclosporine, toxicity, Immunosuppressive Agents, Kidney, pathology, Kidney Cortex, Kidney Diseases, chemically induced, prevention & control, Kidney Medulla, Male, Rats, Rats, Sprague-Dawley, Time Factors

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          Abstract

          Thirty male Sprague-Dawley rats were given ciclosporin (Cs) orally, 15 mg/kg daily for 80 days. Fifteen served as positive controls, while the other 15 were given daily colchicine at a dose of 30 microg/kg in addition to Cs. Additional 15 rats were given olive oil only and served as negative controls. The animals were subjected every other week to laboratory assessment of serum creatinine, sodium, potassium, and Cs whole-blood trough levels; also urine samples were examined for creatinine, sodium, potassium, and protein concentrations. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. Comparing negative control versus Cs-treated and Cs-plus-colchicine-treated rats, there were no significant differences in serum creatinine, creatinine clearance, and serum and urine values of sodium and potassium as well as urinary protein/creatinine ratios. Yet histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner stripe of the outer medulla in all Cs-treated animals and in only 1 of the colchicine-treated group, but in none of the negative controls. Histological changes in other kidney zones in different animal groups were minor and not different. From this study, we may conclude that colchicine is of protective value against chronic Cs nephrotoxicity in Sprague-Dawley rats.

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          Colchicine in acute gout. Reassessment of risks and benefits.

          Colchicine is an effective and relatively specific treatment for acute gout and has a long, venerable history. Serious toxic reactions to colchicine could be prevented if guidelines for its use were followed strictly, but because of its relatively infrequent use and conflicting recommendations, considerable toxic effects might occur and still be undetected by passive surveillance. A review of a teaching hospital's four years' experience showed two deaths (2% incidence) due to inappropriate use. Colchicine has the smallest benefit-to-toxicity ratio of drugs that are effective for acute gout. This article gives specific recommendations for the use of colchicine in different clinical settings.
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