Effect of ketoacids on H2O2 induced cataract

Abstract

Cataract is one of the leading causes of visual disability often leading to blindness in the elderly population. One of the causes is oxidation of proteins present in lens, by hydrogen peroxide (H202 ). In the present study 100 goat lenses were analyzed to determine the protective efficacy of ketoacids, against the oxidative insult by H202. The ketoacids used were (pyruvate, alpha ketoglutarate and oxaloacetate), that are constantly produced endogenously. The lenses were incubated as control and experimental groups in TC-199 media for 72 hrs. H202 concentration of 10mM was used to induce cataract. The biochemical parameters measured were levels of malondialdehyde (MDA), a lipid peroxidation product and activity of glutathione peroxidase (G-Px), an enzymatic antioxidant. The results showed a significant increase in the levels of MDA and significant decrease in the activity of G-Px in the cataractous lenses as compared to control. After addition of ketoacids (pyruvate (10mM), alpha ketoglutarate (20mM) and oxaloacetate (20mM)) separately, the levels of MDA decreased significantly and the activity of G-Px increased significantly. The results suggest that the ketoacids can be very promising antioxidants for the treatment of cataract. They may also be useful in treating other disabilities related to acute and chronic oxidative stress.

Assessment of antioxidant properties of alpha-keto acids in vitro and in vivo

“…The beneficial effects of pyruvate, OA and AKG attributed to its antioxidant properties have been previously demonstrated with other model systems in vivo and vitro [6,10,[12][13][14][15][16][17][18]. The protective effects of alpha-keto acids against menadione-induced DNA injury and cytotoxicity in the human breast cancer cell line were reported among these studies [15].…”

“…During last decades, their protective role against various stressful factors accompanied by oxidative stress development was demonstrated in different models in vivo and in vitro [6,7,[10][11][12][13][14][15][16][17][18]. The detailed mechanisms of such beneficial effects of KAs are not fully established, although their antioxidant role is offered.…”

“…Similar effects were demonstrated for other keto acids such as oxaloacetate (OA) and pyruvate which are intermediates in Krebs cycle and aerobic glycolysis, respectively. In part, exogenous OA reduced iron-induced lipid peroxidation in rat brain in vitro [12], and both OA and pyruvate could moderate the level of lipid peroxidation products in H 2 O 2 -induced cataract [13]. Exogenous pyruvate was revealed to protect against oxidative damages to the eye lens in vitro [14], isolated and cellular DNA [15] and H 2 O 2 -induced cytotoxicity [16][17][18].…”

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

“…It includes diene conjugates, lipid hydroperoxides, oxy-derivatives of phospholipid fatty acids and lipid moieties of aqueous humour and lenses of senile patients [12]. Cataract may also result from accumulation of advanced glycation end product (AGE) [13], decreased of antioxidant defense [14] and increase liberation of free radicals [15].…”

Current Trends in the Pharmacotherapy of Cataracts

“…Both pyruvate and oxaloacetate serve as precursors for the synthesis of several essential and nonessential amino acids. Interestingly, pyruvate (10 mM), α-ketoglutarate(20 mM), and oxaloacetate (20 mM) decreased the level of lenticular lipid peroxidation and enhanced activity of GSH-peroxidase in H2O2 (10 mM)-induced cataract formation in cultured goat lenses [104]. Similarly, pyruvate attenuated in H2O2 (10 mM)-induced lipid peroxidation and enhanced SOD, CAT, and GSHperoxidase activity in cultured goat lenses [87].…”