Desferal-Mn(III) in the therapy of diquat-induced cataract in rabbit.
In rabbit lenses subjected to oxidative stress, induced by 1 mM diquat in vitro, there were 7- to 10-fold increases (p less than 0.001) in malondialdehyde, conjugated dienes, and carbonyl dienes, indicating extensive peroxidation of cellular membrane lipids, and approximately a 60% decrease in reduced glutathione. In the presence of 0.1-5 mM Desferal-Mn(III) these changes were diminished by 50-70%. In an experimental group of 12 rabbits having diquat-induced cataract, Desferal-Mn(III) (5% w/v) applied topically as a 50-microliters eye drop four times per day and a single intraperitoneal dose of 64 mg/kg body wt daily for 5 weeks (including pretreatment for 1 week) retarded the progression of lens opacities, whereas, in a control group of 6 rabbits treated with the vehicle (0.15 M NaCl) cataract progressed to an advanced grade. Treatment with Desferal-Mn(III) also significantly diminished production of O2.- and OH. in the lens, aqueous humor, and vitreous humor, and of H2O2 in the aqueous humor and vitreous humor. It also suppressed lipid peroxidation and oxidation of protein-SH of the lens and restored lenticular glutathione and ascorbate to normal levels.
Bhuyan
K C
KC
Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York 10029.
Bhuyan
D K
DK
Chiu
W
W
Malik
S
S
Fridovich
I
I
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced / Q000188:drug therapy*; D003676:Deferoxamine / Q000627:therapeutic use* / Q000031:analogs & derivatives; D004178:Diquat / Q000633:toxicity*; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007700:Kinetics; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D009924:Organ Culture Techniques; D009942:Organometallic Compounds / Q000627:therapeutic use; D011817:Rabbits
D005609:Free Radicals; D006878:Hydroxides; D008563:Membrane Lipids; D009942:Organometallic Compounds; C068338:manganese desferioxamine; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D004178:Diquat; D006861:Hydrogen Peroxide; D005978:Glutathione; D003676:Deferoxamine; D001205:Ascorbic Acid