Ginevri F, Ghiggeri G M, Oleggini R, Barbano G, Bertelli R, Candiano G, Perfumo F, Gusmano R
Department of Nephrology, G. Gaslini Institute of Genoa, Italy.
Nephrol Dial Transplant. 1990;5 Suppl 1:63-5. doi: 10.1093/ndt/5.suppl_1.63.
Proteinuria and renal xanthine metabolising enzymes, xanthine oxidase and xanthine dehydrogenase, were evaluated in Adriamycin-treated rats fed standard (21% casein) and low-protein (6% casein) diets. In rats fed a standard diet Adriamycin was associated with increased activities in the kidney of xanthine oxidase and xanthine dehydrogenase and induced massive proteinuria. The pharmacological block of both enzymes by allopurinol and tungsten block of both enzymes by allopurinol and tungsten reduced proteinuria to one-third of the original levels. Rats fed a low-protein diet presented decreased levels of renal xanthine oxidase and xanthine dehydrogenase and were only slightly proteinuric. Finally, rats shifted from a low-protein diet to a normal one developed massive proteinuria in spite of normal or slightly decreased levels of renal xanthine oxidase and xanthine dehydrogenase. We conclude that a low-protein diet is effective in decreasing the levels of xanthine metabolising enzymes that are in part responsible for the renal damage due to Adriamycin. This is not however the unique mechanism by which the low-protein diet protects against the development of proteinuria in Adriamycin nephrosis; other factors must also be hypothesised.
在喂食标准(21%酪蛋白)和低蛋白(6%酪蛋白)饮食的阿霉素处理大鼠中,对蛋白尿以及肾脏中的黄嘌呤代谢酶(黄嘌呤氧化酶和黄嘌呤脱氢酶)进行了评估。在喂食标准饮食的大鼠中,阿霉素与肾脏中黄嘌呤氧化酶和黄嘌呤脱氢酶活性增加以及大量蛋白尿的诱导有关。别嘌呤醇对这两种酶的药理学阻断以及别嘌呤醇和钨对这两种酶的钨阻断使蛋白尿减少至原始水平的三分之一。喂食低蛋白饮食的大鼠肾脏黄嘌呤氧化酶和黄嘌呤脱氢酶水平降低,仅有轻微蛋白尿。最后,从低蛋白饮食转为正常饮食的大鼠尽管肾脏黄嘌呤氧化酶和黄嘌呤脱氢酶水平正常或略有下降,但仍出现大量蛋白尿。我们得出结论,低蛋白饮食可有效降低黄嘌呤代谢酶的水平,这些酶部分导致了阿霉素引起的肾脏损伤。然而,这并非低蛋白饮食预防阿霉素肾病中蛋白尿发生的唯一机制;还必须假设有其他因素。