Studies on retinotoxic potential of a novel antitumor antibiotic--sparsomycin--in rats.
Sparsomycin (Sm) is a potent inhibitor of protein synthesis with an anticancer potential. Two years after its discovery in 1962 a phase I clinical trial revealed serious drug-induced retinotoxicity. The mechanism of this toxicity still remains unresolved; however, its understanding is important for the reintroduction of Sm or one of its analogues in clinical practice. If Sm penetrates the retina, its toxic effect should be seen as inhibition of a protein(s) vital for the visual function. Treatment of healthy albino rats and Royal College of Surgeon (RCS) rats with subtoxic doses of Sm was unable to produce ocular toxic effects. Disruption of the blood-retina barrier with sodium iodate allowed Sm to decrease opsin content by only 27%. These results strongly indicate that Sm might become retinotoxic solely upon extreme conditions such as permeabilization of the blood-retina barrier which may happen only in some rare pathological situations.
Zylicz
Z
Z
Department of Internal Medicine, St. Radboud University Hospital, Nijmegen, The Netherlands.
De Grip
W J
WJ
Wagener
D J
DJ
Van Rennes
H
H
Van Der Kleijn
E
E
Van Den Broek
L A
LA
Ottenheijm
H C
HC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D005136:Eye Proteins / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012243:Rhodopsin / Q000378:metabolism; D017299:Rod Opsins; D013033:Sparsomycin / Q000097:blood / Q000633:toxicity*
D000903:Antibiotics, Antineoplastic; D005136:Eye Proteins; D017299:Rod Opsins; D013033:Sparsomycin; D012243:Rhodopsin