Formation of micronucleated erythrocytes in mouse bone-marrow under conditions of hypothermia is not associated with stimulation of erythropoiesis.
Conditions of marked and long-lasting hypothermia have been shown to increase the formation of micronucleated polychromatic erythrocyte (MNPCE) in mouse bone-marrow. Stimulation of erythropoiesis as a consequence of anoxic conditions associated with decreased body temperature has been suggested as a possible mechanism for hypothermia-induced micronucleus formation. We examined whether chemically induced hypothermic conditions that produced increased MNPCE formation were associated with stimulation of erythropoiesis by measuring erythropoietin (EPO) concentrations in blood. Marked and long-lasting hypothermia was induced in male mice by oral administration of the antipsychotic compounds E-5842 (200 mg/kg) or chlorpromazine (100 mg/kg). Maximum decreases from the basal temperature, achieved 8 h after treatment, were 14.8 and 12.8 degrees C, respectively. A statistically significant increase in bone-marrow MNPCE frequency was observed 48 h after administration of E-5842 (p<0.01) or chlorpromazine (p<0.05). Mice made anaemic by retro-orbital bleeding (0.5 ml), which acted as positive control for stimulation of erythropoiesis, showed no relevant variation in mean rectal temperature and a slight non-statistically significant increase in MNPCE frequency after 48 h. Blood samples for determination of EPO levels were obtained 4 (bleed-control animals only), 8, 16 and 24 h after treatment. In spite of the induced hypothermia, no significant variation in EPO blood levels was observed after administration of E-5842 or chlorpromazine. Bleed-induced anaemic mice showed a clear increase in EPO blood levels at all sampled time points, differences from baseline values being statistically significant (p<0.001) at the 8-h samplings and beyond. These results indicate that induction of MNPCE secondary to chemically induced hypothermia is not mediated by stimulation of erythropoiesis.
Guzmán
Antonio
A
Toxicology Department, ESTEVE, Mare de Déu de Montserrat 221, 08041 Barcelona, Spain. aguzman@esteve.es
García
Concepción
C
Marín
Ana-Paz
AP
Tortajada
Araceli
A
Ruiz
María Teresa
MT
Fernández de Henestrosa
Antonio R
AR
Marcos
Ricard
R
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D002746:Chlorpromazine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000097:blood; D007035:Hypothermia / Q000139:chemically induced*; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D011725:Pyridines / Q000494:pharmacology*; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; C117757:E 5842; D011725:Pyridines; D014230:Triazoles; D004921:Erythropoietin; D002746:Chlorpromazine