Edmands S D, Hughs K S, Lee S Y, Meyer S D, Saari E, Yancey P H
Biology Department, Whitman College, Walla Walla, Washington, USA.
Kidney Int. 1995 Aug;48(2):344-53. doi: 10.1038/ki.1995.302.
Sorbitol plus myo-inositol, betaine and glycerophosphorylcholine (GPC) are cellular osmolytes in the mammalian renal medulla. Galactosemia and hyperglycemia can cause excessive levels of galactitol or sorbitol in several organs via aldose reductase (AR) catalysis. AR inhibitors can reduce these polyols. To examine osmolyte responses to polyol perturbations, male Wistar rats were fed normal diet, the AR inhibitor sorbinil (at 40 mg/kg/d), 25% galactose, or a combination, for 10, 21 and 42 days. All animals at 21 days had higher apparent renal AR activity than at 10 or 42 days, possibly providing resistance to sorbinil. Sorbinil feeding alone tended to increase urinary, plasma and renal urea levels. It reduced AR activity and sorbitol contents in renal inner medulla, though less so at 21 days; other renal osmolytes, especially betaine, were elevated. Galactose feeding caused little change in renal AR activity, and resulted in high galactose and galactitol contents in renal medulla, urine, blood and lens (and higher renal Na+ contents at 10 days). Renal sorbitol, inositol and GPC decreased, while betaine contents trended higher at all times. Sorbinilgalactose feeding reduced renal AR activities and galactitol contents (again less so at 21 days), urine, blood and lens galactitol, and further reduced renal sorbitol contents. At 10 and 21 days it tended to raise renal betaine more, and restore inositol (but not GPC) contents to control levels. At 42 days it reduced renal and urinary Na+ and galactose, and decreased renal betaine to control levels. Under most conditions, total renal (non-urea) organic osmolyte contents (presumed to be mostly intracellular) and Na+ plus galactose contents (presumed mostly extracellular) changed together such that cell volumes may have been maintained. The exception was 10 days on galactose, where total osmolytes appeared too low. In galactose-fed animals, urine/plasma ratios suggest some renal galactitol efflux, and cellular galactitol probably helps maintain osmotic balance rather than cause swelling.
山梨醇与肌醇、甜菜碱和甘油磷酰胆碱（GPC）是哺乳动物肾髓质中的细胞渗透溶质。半乳糖血症和高血糖症可通过醛糖还原酶（AR）催化在多个器官中导致半乳糖醇或山梨醇水平过高。AR抑制剂可减少这些多元醇。为了研究渗透溶质对多元醇紊乱的反应，将雄性Wistar大鼠分别喂食正常饮食、AR抑制剂索比尼尔（40毫克/千克/天）、25%半乳糖或它们的组合，持续10天、21天和42天。所有21天的动物肾AR活性均高于10天或42天的动物，这可能是对索比尼尔产生了抗性。单独喂食索比尼尔往往会增加尿液、血浆和肾脏中的尿素水平。它降低了肾内髓质的AR活性和山梨醇含量，尽管在21天时降低程度较小；其他肾脏渗透溶质，尤其是甜菜碱，含量升高。喂食半乳糖对肾脏AR活性影响不大，但导致肾髓质、尿液、血液和晶状体中的半乳糖和半乳糖醇含量升高（10天时肾脏Na+含量也更高）。肾脏中的山梨醇、肌醇和GPC减少，而甜菜碱含量在所有时间均呈上升趋势。索比尼尔-半乳糖联合喂食降低了肾脏AR活性和半乳糖醇含量（同样在21天时降低程度较小）、尿液、血液和晶状体中的半乳糖醇，并进一步降低了肾脏山梨醇含量。在10天和21天时，它往往会使肾脏甜菜碱升高更多，并使肌醇（但不是GPC）含量恢复到对照水平。在42天时，它降低了肾脏和尿液中的Na+和半乳糖，并使肾脏甜菜碱降至对照水平。在大多数情况下，肾脏（非尿素）总有机渗透溶质含量（推测大多为细胞内）和Na+加半乳糖含量（推测大多为细胞外）共同变化，从而可能维持细胞体积。例外情况是喂食半乳糖10天时，总渗透溶质似乎过低。在喂食半乳糖的动物中，尿/血浆比值表明肾脏有一些半乳糖醇外流，细胞内的半乳糖醇可能有助于维持渗透平衡而非导致肿胀。
