Cataractogenic effects in rats following chronic administration of SDZ ICT 322, a selective 5-HT3 antagonist.
SDZ ICT 322, an indole-3-carboxylic acid scopine ester developed for the treatment of delayed gastric emptying, was administered in feed to four groups of 14 male and 14 female Wistar rats at daily doses of 0, 5, 25 or 125 mg/kg/day for 26 weeks. Clinical and periodic ophthalmic examinations, hematology, clinical biochemistry, and urinalysis were performed. Eyes were examined for histopathologic and electronmicroscopic alterations as well as for reduced glutathione (GSH) and oxidized glutathione (GSSG) levels. Skin effects with hair loss, hyperemia, and desquamation were found in the majority of the high-dose rats. At study termination, bilateral posterior lens opacities had developed in 26 of the 28 high-dose rats. Histopathologically, grossly irregular and fragmented lens fibres were observed. Severe vacuolization of the lens epithelium was seen electronmicroscopically. The GSH/GSSG ratio was statistically significantly reduced in lenses of mid- and high-dose animals. Since decreased GSH/GSSG ratio is an established indicator for increased oxygen radical generation, these data suggest a possible role of oxidative stress in cataracts induced by SDZ ICT 322.
Längle
U W
UW
Sandoz Pharma Ltd., Toxicology, Basel, Switzerland.
Wolf
A
A
Kammüller
M E
ME
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002386:Cataract / Q000139:chemically induced*; D005123:Eye / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism; D019803:Glutathione Disulfide; D007211:Indoles / Q000633:toxicity*; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000633:toxicity; D012702:Serotonin Antagonists; D012867:Skin / Q000187:drug effects; D013997:Time Factors
D007211:Indoles; D017382:Reactive Oxygen Species; D012702:Serotonin Antagonists; C084870:SDZ ICT 322; D005978:Glutathione; D019803:Glutathione Disulfide