Gabapentin Attenuates Oxidative Stress and Apoptosis in the Diabetic Rat Retina

• Published in: Neurotoxicity research 2019-07, Vol.36 (1), p.81-90
• Main Authors: Ola, Mohammad Shamsul, Alhomida, Abdullah S., LaNoue, Kathryn F.
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; Animals; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cell Biology; Diabetes Mellitus, Experimental - metabolism; Diabetic Retinopathy - metabolism; Disease Models, Animal; Gabapentin - administration & dosage; Glutamic Acid - metabolism; Glutathione - metabolism; Lipid Peroxidation; Neurobiology; Neurochemistry; Neurology; Neurosciences; Original Article; Oxidative Stress - drug effects; Pharmacology/Toxicology; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Streptozocin - administration & dosage; Transaminases - antagonists & inhibitors
• ISSN: 1029-8428; 1476-3524
• DOI: 10.1007/s12640-019-00018-w

Neurodegeneration in diabetic retina has been widely considered as initiating factor that may lead to vascular damage, the classical hallmark of diabetic retinopathy. Diabetes induced altered glutamate metabolism in the retina, especially through glutamate excitotoxicity might play a major role in the neurodegeneration. Increased level of branched chain amino acids (BCAAs) measured in diabetic retina might cause an increase in the neurotoxic level of glutamate by transamination of citric acid cycle intermediates. In order to analyze the transamination of BCAAs and their influence on neurodegenerative factors, we treated streptozotocin-induced diabetic rats with gabapentin, a leucine analogue and an inhibitor of branched chain amino transferase (BCATc). Interestingly, gabapentin lowered the retinal level of BCAAs in diabetic rats. Furthermore, gabapentin treatments ameliorated the reduced antioxidant glutathione level and increased malondialdehyde (MDA), the marker of lipid peroxidation in diabetic rat retinas. In addition, gabapentin also reduced the expression of proapoptotic caspase-3, a marker of apoptosis and increased anti-apoptotic marker Bcl-2 in diabetic retinas. Thus, these results suggest that gabapentin stimulates glutamate disposal, and ameliorates apoptosis and oxidative stress in diabetic rat retina. The influence of gabapentin may be due to its capacity to increase the ratio of BCKA to BCAA which in turn would reduce glutamate excitotoxicity in diabetic retina.