Differential expression of the lenticular antioxidant system in laboratory animals: a determinant of species predilection to oxidative stress-induced ocular toxicity?
OBJECTIVE
Various animal species have been used to study oxidative stress-induced cataractogenesis; however, given that differences in the expression of the lens antioxidant system may influence species susceptibility to oxidative stress, we compared and contrasted a broad spectrum of components of the lens antioxidant system in dog, rat, marmoset, and rabbit.


METHODS
Lenses collected from beagle dogs, Sprague-Dawley rats, marmosets, and New Zealand white rabbits were assayed for reduced glutathione (GSH), and activities of copper-zinc and manganese superoxide dismutase (CuZn-SOD; Mn-SOD), catalase (CAT), glutathione peroxidase (GPX), gamma-Glutamylcysteine synthetase (GCS), glutathione reductase (GR), glutathione-S-transferases (GST), and glucose-6-phosphate dehydrogenase (GPDH), and Trolox equivalent antioxidant capacity (TEAC).


RESULTS
Expression of the lens antioxidant system varied considerably between species. Marmoset lens contained the highest levels of GSH, its respective biosynthetic and recycling enzymes GCS and GR, and the associated H(2 )O(2)-dismutation enzyme GPX. Activities of both SOD isoforms were also highest in marmoset lens. However, activities of the xenobiotic-conjugating enzyme GST and NADPH-generating enzyme GPDH were relatively low. In contrast, dog lens had the lowest levels of GSH, GCS, GR, and Cu-Zn SOD (1/2, 1/2 and 1/33, and 1/63 that in marmoset) but highest levels of GST and GPDH. Rabbit lens contained the highest CAT activity, at up to 3.5-fold that for marmoset and rat.


CONCLUSIONS
These results demonstrate substantial variation in lens antioxidant systems between different laboratory animal species. Given that such variation may affect relative susceptibility to oxidative stress-mediated ocular toxicity, our findings may provide useful information when choosing different animal species for lens research.
Slaughter
Mark R
MR
Safety Assessment, GlaxoSmithKline, Ware, UK. mark_slaughter@sandwich.pfizer.com
Thakkar
Hansa
H
O'Brien
Peter J
PJ
D000818:Animals; D000830:Animals, Laboratory / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D002144:Callithrix; D004285:Dogs; D005128:Eye Diseases / Q000209:etiology; D005260:Female; D014644:Genetic Variation; D007908:Lens, Crystalline / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D000975:Antioxidants