Toxicity study in rats of a tellurium based immunomodulating drug, AS-101: a potential drug for AIDS and cancer patients.
Male and female Sprague Dawley rats were injected intraperitoneally for 4 weeks with ammonium trichloro (dioxyethylene-0-0'-) tellurate, an immunomodulating drug at doses ranging from 3 to 24 mg/kg/week. Routine laboratory examinations included body weight, food consumption, clinical chemistry and hematological examinations. At termination of the experiment, all rats were sacrificed and subjected to a detailed necropsy. Few mortalities were recorded during the course of the study. Clinical signs included hind limb paresis and paraphimosis. A garlic odor pervaded the room. Body weight and food consumption were adversely affected in a dose-related manner. Effects were elicited on the hematological system; changes being noted in the platelet and leukocyte counts as well. Clinical chemistry evaluation revealed signs of hepatoxicity, especially in the female treated groups. The level of beta-globulin was increased. At necropsy organs were found to have a grayish-blue discoloration. Tellurium related histopathological changes were observed in the eyes, liver, thymus, bone marrow, heart and kidneys. An attempt has been made to compare the toxicity of this drug with other tellurium-containing compounds. A good correlation was found. Novel effects of the drug were retinopathy and replacement of bone marrow by bony or fibrous tissue. The possibility that some of the effects may have been elicited due to selenium-vitamin E deficiency has been considered.
Nyska
A
A
Life Science Research Israel, Ness Ziona.
Waner
T
T
Pirak
M
M
Albeck
M
M
Sredni
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000276:Adjuvants, Immunologic / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D004435:Eating / Q000187:drug effects; D005030:Ethylenes; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D010024:Osteoporosis / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000473:pathology; D013154:Spleen / Q000473:pathology; D013691:Tellurium / Q000633:toxicity*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D005030:Ethylenes; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; D013691:Tellurium