Effect of agroclavine on NK activity in vivo under normal and stress conditions in rats.
Agroclavine is a natural, clavine type of ergot alkaloid with D1 dopamine and a-adrenoceptor agonistic properties. We showed previously that in vitro agroclavine enhances natural killer (NK) cell activity, increases interleukin-2 and interferon-gamma production and prolongs the survival time of tumor-bearing mice. The aim of this study was 1) to test the effect of agroclavine on NK activity in vivo, and 2) to assess the potential toxicity of high doses of agroclavine on cardiac and liver functions using creatine kinase MB (CKMB) and alanine aminotransferase (ALT) as biochemical markers in normal and stressed animals. The effect of stress was studied because we examined promising anticancer properties of agroclavine and malignant diseases are supposed to be a potent stressful event for patients. In our experiments 3-month-old male rats of the Wistar-Kyoto strain were used. Agroclavine was injected intraperitoneally (0.5 mg/kg or 0.05 mg/kg) 30 min before stress (four hours' restraint and immersion in 23 degrees C water). The animals were killed 30 min after stress, blood was collected and the spleen was removed. Non-stressed animals treated with agroclavine were killed 5 h after the drug administration. The results confirmed our previous in vitro results and showed that also in vivo agroclavine increases NK cell activity under non-stress conditions. Agroclavine only slightly increased CKMB and had no influence on ALT in non-stressed animals. These promising results are limited by the fact that agroclavine (0.5 mg/kg) diminished NK cell activity and significantly increased ALT and CKMB under stress conditions.
Starec
M
M
Department of Pharmacology, Third Academy of Sciences, Prague, Czech Republic. Miroslav.Starec@LF3.cuni.cz
Fiserová
A
A
Rosina
J
J
Malek
J
J
Krsiak
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D003402:Creatine Kinase / Q000097:blood; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006331:Heart Diseases / Q000139:chemically induced / Q000175:diagnosis; D007101:Immersion; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008107:Liver Diseases / Q000175:diagnosis; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000209:etiology
D000903:Antibiotics, Antineoplastic; D004873:Ergolines; C004465:agroclavine; D000410:Alanine Transaminase; D003402:Creatine Kinase