Identification of galactitol 2-phosphate and galactitol 3-phosphate in the lens of galactose-fed rats

Kappler, Francis; Su, Bangying; Szwergold, Benjamin S.; Randall, William C.; Brown, Truman R.

doi:10.1016/0026-0495(95)90069-1

Cited by 5 publications

(1 citation statement)

References 18 publications

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“…Increased oxygen radicals initiate lipid peroxidation, which, in turn, stimulate protein glycation [46,47]. Furthermore, galactitol can be metabolized to galactitol-2-phosphate and galactitol-3-phosphate [48], which could be potent protein-glycating agents like fructose-3-phosphate [49]. Therefore, increased oxidative stress and the following acceleration of glycation in galactosaemia could be involved in the intimal thickening of coronary arteries.…”

Section: Discussionmentioning

confidence: 99%

An aldose redutase inhibitor prevents the intimal thickening in coronary arteries of galactose-fed beagle dogs

et al. 1999

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Macrovascular complications such as myocardial infarction, angina pectoris and cerebrovascular accidents are the major causes of mortality in diabetic patients [1,2]. Although the maintenance of a good glycaemic control for a long period can decrease the risk of the development of diabetic microangiopathy [3], the development of diabetic macroangiopathy cannot be prevented by glycaemic control [3,4]. Therefore, it is very important to establish the pathogenesis of diabetic macroangiopathy.Various hypotheses including increased polyol pathway activity, protein kinase C (PKC) activation, increased oxidative stress and enhanced non-enzymatic glycation have been implicated in the pathogenesis of diabetic microangiopathy such as retinopathy, nephropathy and neuropathy [5,6]. Hyperglycaemia-induced metabolic alterations could also contribute to the development of diabetic macroangiopathy. Although the importance of the latter three metabolic deficits in the pathogenesis of diabetic macroangiopathy have been investigated precisely [7±12], the relation between polyol pathway hyperactivity and diabetic macroangiopathy remains unclear. Diabetologia (1999) Abstract Aims/hypothesis. Although increased polyol pathway activity has been implicated in the pathogenesis of diabetic microangiopathy, the relation with diabetic macroangiopathy remains unclear. Galactose feeding is known to stimulate the polyol pathway and to develop abnormalites similar to those in diabetic microangiopathy. Our study was conducted to investigate whether an activation of polyol pathway by long-term treatment with galactose produced morphological changes in coronary arteries of dogs and the effect of an aldose reductase inhibitor, epalrestat, was also studied. Methods. Dogs received either normal chow or chow containing 30 % galactose with or without epalrestat given orally (20 or 50 mg × kg ±1 ). After 44 months, morphometric analyses of coronary arteries were carried out and the galactitol contents in aortas were measured.Results. The ratio of areas of the intimal layer to those of the medial layer, an indicator of intimal thickening, was statistically significantly increased in galactosefed dogs compared with control dogs. Galactose-fed dogs had a remarkable accumulation of galactitol in their aortas. These morphological and biochemical deficits were reduced by treatment with epalrestat. Conclusion/interpretation. This report morphologically shows diabetes-like macrovascular abnormalities in galactosaemic animals, suggesting that polyol pathway hyperactivity is closely related to the development of diabetic macroangiopathy, which could be prevented by aldose reductase inhibition. [Diabetologia (1999

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