Kern H L, Bellhorn R W, Peterson C M
J Pharmacol Exp Ther. 1977 Jan;200(1):10-6.
Ocular lesions secondary to sodium cyanate administration in the beagle are described. Fifteen dogs were given sodium cyanate at doses of 30 to 170 mg/kg/day, 5 days per week. Fourteen developed cataracts which were generally posterior and subcapsular. Five animals developed corneal lesions. Control beagles and cyanate-treated rats and monkeys did not develop lesions. The one drug-treated beagle without ocular lesions received a maximum dose of 30 mg/kg/day of sodium cyanate for 19 months and achieved a mean carbamylatin of 0.39 residue of cyanate per mol of hemoglobin. Animals developing cataracts received a maximum dose of 119+/-23 mg/kg/day for 28+/-10 months and achieved a mean carbamylation of 0.69+/-0.13 residue/mol. Animals developing corneal lesions received a maximum dose of 113+/-22 mg/kg/day for 36+/-7 months and achieved a mean carbamylation of 0.78+/-0.09 residue/mol. Younger animals appeared more susceptible to the cataractogenic effects of the drug than older ones. Lens intracellular sodium was increased by 100% in the cataractous lenses while potassium was significantly decreased in the lenses with the greatest opacity. Extracellular space was increased in the cataractous lenses by 61%. Reduced glutathione levels were decreased by 34% and lactate leakage into the medium was increased by 12%. Rubidium-86 uptake was increased by 26% in the cataractous lenses, probably reflecting an inadequate compensatory response to increased passive fluxes of cations resulting from a structural or enzymatic lesion.
描述了比格犬因服用氰酸钠而继发的眼部病变。15只犬每周5天,以30至170毫克/千克/天的剂量服用氰酸钠。14只犬出现白内障,通常为后囊下白内障。5只动物出现角膜病变。对照比格犬以及经氰酸盐处理的大鼠和猴子未出现病变。一只接受药物治疗但无眼部病变的比格犬,以30毫克/千克/天的最大剂量服用氰酸钠19个月,每摩尔血红蛋白的氰酸盐氨甲酰化平均残留量为0.39。出现白内障的动物,以119±23毫克/千克/天的最大剂量服用28±10个月,每摩尔的氨甲酰化平均残留量为0.69±0.13。出现角膜病变的动物,以113±22毫克/千克/天的最大剂量服用36±7个月,每摩尔的氨甲酰化平均残留量为0.78±0.09。年幼动物似乎比年长动物对该药物的致白内障作用更敏感。白内障晶状体中的晶状体细胞内钠增加了100%,而在不透明度最高的晶状体中钾显著减少。白内障晶状体的细胞外间隙增加了61%。还原型谷胱甘肽水平降低了34%,乳酸向培养基中的渗漏增加了12%。白内障晶状体中铷-86的摄取增加了26%,这可能反映了对因结构或酶损伤导致的阳离子被动通量增加的代偿反应不足。