Modelling cortical cataractogenesis 22: is in vitro reduction of damage in model diabetic rat cataract by taurine due to its antioxidant activity?
The protective effect of taurine in model in vitro diabetic cataract and the mechanism of this effect were investigated in isolated rat lenses. Isolated rat lenses were incubated in medium 199 in elevated glucose (55.6 m m) with taurine (5 m m). Taurine concentrations in the lenses were determined by amino acid analysis. Accumulative leakage of the intracellular enzyme lactate dehydrogenase (LDH) was used to estimate damage to the lens, as previously reported. In the clear lenses, prior to vacuole formation, after 1 or 2 days of incubation, the taurine and amino acids in lenses decreased progressively in concentration. In lenses incubated with 5 m m taurine, the level of taurine was increased towards that of control lenses. In taurine-treated lenses LDH leakage was significantly decreased, and lens clarity was maintained, similarly to that found previously for vitamin C and lipoic acid. To test whether taurine has similar antioxidant activity, we tested its ability to decrease luminol luminescence generated by (1) superoxide from hypoxanthine/xanthine oxidase and (2) peroxide from diluted glucose/glucose oxidase. For either superoxide or peroxide, the luminescence was decreased to zero, as a function of increasing taurine concentration, at 30 m m, approximately the physiological concentration of taurine in the lens. Spin trapping confirmed that taurine scavenged superoxide. This is consistent with a role for taurine as an important antioxidant protecting the lens against oxidative insults. Amino acids also had antioxidant activity in this assay, and as a group, when all activities were summed, their loss also contributed significantly to the antioxidant loss. Taken in conjunction with Wolff and Crabbe's observation of increased free radical generation by glucose auto-oxidation in diabetes, this suggests a push-pull mechanism for increased oxidative stress in diabetic cataract, involving both increased free radicals and decreased radical scavenging antioxidants.
Kilic
F
F
Department of Biochemistry, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Bhardwaj
R
R
Caulfeild
J
J
Trevithick
J R
JR
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002386:Cataract / Q000209:etiology / Q000378:metabolism*; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*
D000596:Amino Acids; D000975:Antioxidants; D013481:Superoxides; D013654:Taurine; D007770:L-Lactate Dehydrogenase; D005947:Glucose