Biochemical changes induced by intravitreally-injected doxorubicin in the iris-ciliary body and lens of the rabbit eye.
The aim of this study was to examine the chronic effects and mode of action of doxorubicin in ocular tissues. A dose of 10 microg (17.24 nanomoles) of doxorubicin hydrochloride in 20 microl sterile saline were intravitreally injected, under local anaesthesia, in one eye of 13 rabbits and 50 microg (86.20 nanomoles) were similarly injected in one eye of 3 rabbits. The contralateral eye received 20 microl of saline only. The dose of 50 microg induced initially mild uveal inflammation which became chronic and turned into circular iritis. Both doses of the drug induced cataract of the lens and clouding of the cornea within 2-3 months. The activity of superoxide dismutase, in iris-ciliary bodies and lenses treated with either 10 or 50 microg of the compound, was significantly lower relative to that in respective control tissues. In contrast to superoxide dismutase, catalase showed an increased activity in experimental tissues relative to control. The lysosomal hydrolases acid phosphatase, N-acetyl-B-D-glucosaminidase, aryl sulphatase and acid cathepsin, all showed significantly elevated activities in iris-ciliary body tissues one year after injection with the 50 microg doxorubicin. The reduction in superoxide dismutase activity may render ocular tissues susceptible to peroxidative attack and the increased activities of lysosomal hydrolases may contribute to chronic cell injury and inflammation.
Phylactos
A C
AC
Institute of Brain Chemistry and Human Nutrition, University of North London, UK.
Unger
W G
WG
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D003318:Corneal Opacity / Q000139:chemically induced* / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D005136:Eye Proteins / Q000378:metabolism; D005500:Follow-Up Studies; D007267:Injections; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced* / Q000378:metabolism; D014822:Vitreous Body
D000970:Antineoplastic Agents; D005136:Eye Proteins; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase