Australian Journal of Basic and Applied Sciences, 4(2): 127-134, 2010 ISSN 1991-8178 Corresponding Author: Ghada Ghanem El-Hossary, Pharmacology Department, Research Institute of Ophthalmology, Giza, Egypt. E-mail: gghossary@yahoo.com 127 Efficacy of Alpha-Lipoic Acid against Diabetes-Induced Deterioration of Blood Antioxidants and Diabetic Retinopathy in Experimental Animals Ghada Ghanem El-Hossary, Amany Hassan M. El-Shazly, Nadia Samy Ahmed, Amal Ahmed 1 1 2 3 El-Gohary, Fatma Gamal Metwally and Sawsan Hanafy Karam 4 4 Pharmacology, Nutrition, Physiology and Histology Departments, Research Institute of 1 2 3 4 Ophthalmology, Giza, Egypt. Abstract: The present study aimed to investigate the effect of alpha-lipoic acid (ALA) administration on diabetes-induced alterations of blood antioxidants and retinal histopathological changes. Forty albino Wistar rats of both sexes were used and divided into four groups; two groups (I and II) served as controls. In group III, diabetes was induced by a single intraperitoneal injection of alloxan 100 mg/kg. In group IV, diabetes was induced and rats received a daily oral dose of ALA 60 mg/kg/day for four months. Serum glucose, serum vitamin C and erythrocyte reduced glutathione levels were measured after 2 and 4 months. Then, animals were sacrificed and subjected to light microscopic examination of the retina. Untreated diabetic animals exhibited significant deterioration of the measured biochemical parameters in addition to marked histopathological retinal changes. Treatment with ALA improved significantly the diabetes-induced deterioration of vitamin C and glutathione in blood. In addition, the retina of these animals appeared normal with no significant deviation from the control retina suggesting its protective role against diabetic retinopathy. Key words: Alpha-lipoic acid, experimental diabetes mellitus, antioxidant, diabetic retinopathy, vitamin C, glutathione. INTRODUCTION Diabetic neuropathy represents a major health problem as it is responsible for substantial morbidity, increased mortality and impaired quality of life. Near normoglycemia is now generally accepted as the primary approach for prevention of diabetic neuropathy, but it is not achievable in a considerable number of patients (Ziegler, 2004). In the past two decades several medical treatments that exerted their effects despite hyperglycemia have been derived from the experimental pathogenic concept of diabetic neuropathy. Such compounds have been designed to improve or slow down the progression of the neuropathic process and are being evaluated in clinical trials to achieve the above benefits by many researchers (Negrisanu et al., 1999 and Bregovskii et al., 2005). Alpha-lipoic acid (ALA) and its reduced form dihydro-lipoic acid are present in all prokaryotic and eukaryotic cells. Lipoic acid was once considered a vitamin, but now it is commonly accepted that it can be synthesized de novo in human cells. It has long been known as a coenzyme of multi-enzymatic complexes catalyzing the decarboxylation of alpha keto acids. In addition, ALA is involved in the regulation of carbohydrate and lipid metabolism (Malinska and Winiarska, 2005). Moreover, ALA was found to be a potent free radical scavenger and metal chelator. It also plays an important role in the regeneration of the active form of other cellular antioxidants including vitamins C and E (Biewenga et al., 1997). Being easily absorbed from the gastrointestinal tract and able to cross the blood brain barrier without exhibiting any serious side effects along with the above mentioned features, ALA is considered a very promising drug (Malinska and Winiarska, 2005). Alpha-lipoic acid was used successfully to ameliorate diabetic polyneuropathies in clinical trials (Ziegler, 2004). Negrisanu et al. (1999) have proved its value in improving the nerve conduction velocity and clinical manifestations of diabetic peripheral neuropathy. In addition, Bregovskii et al. (2005) observed an improvement in diabetic sensory deficiency after treatment with ALA. Moreover, Tankova et al.,(2004) reported its