Immunotoxicity of ethyl-4-isothiocyanatobutanoate in male Wistar rats.
The immunotoxicity of ethyl-4-isothiocyanatobutanoate (E-4IB) using different immuno-pathological parameters and immune function assays in male Wistar rats was evaluated. The rats were administered intraperitoneally 12 times with E-4IB in three varying doses of 21, 28 and 35 mg/kg of body weight, over a period of 36 days. The doses of E-4IB were set according to the results of previous experiments by its anti-proliferative activity in vivo. High and medium doses of E-4IB exceeded the maximum tolerated dose after the 36-day treatment period. Symptoms of toxicity were displayed by a drop in body weight, spleen and thymus weight and in organ and bone marrow cellularity. Haematological changes displayed a dose-dependent decrease in the percentage of lymphocytes and dose-dependent increase in the percentage of polymorphonuclear leukocytes in peripheral blood. The white blood cell count in rats exposed to a high dose of E-4IB was suppressed. The immune system of rats administered 21 mg/kg of E-4IB (low dose) was unaffected. No changes in primary antibody response to sheep erythrocytes, in vitro proliferative response of spleen lymphocytes to mitogens and phagocytic activity of leukocytes were found in those rats. Our findings indicate that this newly developed anti-cancer drug is not immunotoxic.
Tulinska
J
J
Department of Immunotoxicology, Institute of Preventive and Clinical Medicine, Limbova 14, 833 01, Bratislava, Slovak Republic. tulinska@upkm.sk
Sovcikova
A
A
Liskova
A
A
Kubova
J
J
Horakova
K
K
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002087:Butyrates; D007109:Immunity / Q000187:drug effects*; D017879:Isothiocyanates / Q000633:toxicity*; D007962:Leukocytes / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D002087:Butyrates; D017879:Isothiocyanates; C082832:ethyl 4-isothiocyanatobutanoate