Abstract
The present study was undertaken to determine oxidative/nitrosative stress in aqueous humor of alloxan-induced hyperglycemic rabbits and to investigate the effects of two oral antidiabetic drugs, pioglitazone from peroxisome proliferator-activated receptor gamma (PPARγ) agonists and repaglinide from nonsulfonylurea KATP channel blockers. Ascorbic acid (AA), glutathione (GSH), total antioxidant status (TAS), lipid peroxidation products (LPO), total nitrites (NO2), advanced oxidized protein products (AOPP), and protein carbonyl groups (PCG) were determined using respective colorimetric and ELISA methods. In our hyperglycemic animals, AA decreased by 77%, GSH by 45%, and TAS by 66% as compared to control animals. Simultaneously, LPO increased by 78%, PCG by 60%, AOPP by 84%, and NO2 by 70%. In pioglitazone-treated animals, AA and TAS increased above control values while GSH and PCG were normalized. In turn, LPO was reduced by 54%, AOPP by 84%, and NO2 by 24%, in relation to hyperglycemic rabbits. With repaglinide, AA and TAS were normalized, GSH increased by 20%, while LPO decreased by 45%. Our results show that pioglitazone and repaglinide differ significantly in their ability to ameliorate the parameters like NO2, PCG, and AOPP. In this area, the multimodal action of pioglitazone as PPARγ agonist is probably essential.
Highlights
The eye is a unique organ since it is constantly exposed to radiation, atmospheric oxygen, environmental chemicals, and physical abrasion
The rabbits were divided into six groups of 5 animals: normal control (Group C), control treated with pioglitazone (Group CP), control treated with repaglinide (Group CR), hyperglycemic (Group H), hyperglycemic treated with pioglitazone (Group HP), and hyperglycemic treated with repaglinide (Group HR)
lipid peroxidation products (LPO) was reduced by 54%, advanced oxidized protein products (AOPP) by 84% and NO2 by 24% in relation to hyperglycemic rabbits
Summary
The eye is a unique organ since it is constantly exposed to radiation, atmospheric oxygen, environmental chemicals, and physical abrasion. The eye provides a unique situation for generation of reactive oxygen species (ROS). Oxidative stress is implicated in the etiology of many ocular diseases such as glaucoma, retinal degeneration, ocular inflammation, cataracts, and diabetic complications [1,2,3]. Nitrogen reactive species (RNS) play an important role in different oxidative alterations [4, 5]. Nitric oxide (NO) is an important messenger in vascular and nervous systems or in immunological reactions including these in the eye. NO formed in excess by inducible NO synthase (iNOS) may cause serious ocular injuries [6]
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