TY - JOUR
T1 - Cisplatin effects on rhythmic functions of mice
T2 - Strain and tissue dependence
AU - Weigl, Yuval
AU - Peleg, Leah
AU - Dotan, Aviva
AU - Ashkenazi, Israel E.
PY - 2012/7
Y1 - 2012/7
N2 - The competence to preserve the optimal timing relationships between rhythmic variables enables adaptation of mammals to alternate environmental conditions. The capability to re-entrain depends on genetic factors and the nature of imposed time cues. In the present study, the authors examined in rodent models, following a cancer chronochemotherapy, cisplatin (CP), the rhythm patterns of locomotor activity and of a few biochemical variables (alkaline phosphatase and creatinine phosphokinase in kidney tissue and plasma, kidney urea nitrogen, and white blood cell count). Males of two inbred mice strains, BALBc and c57Bl6J, received 10 consecutive daily intraperitoneal (i.p.) injections of either saline or CP at zeitgeber time 22 (ZT22). CP administration altered the rhythms of each examined function in both strains. The type and extent of the changes varied among variables, tissuesplasma, and mouse strain. Yet, the effect of CP was not detected on all parameters, but only in ∼60 of them. In addition, in the majority of the studied parameters, BALBc and c57Bl6J mice differed in their response to CP. The temporal parameters of period and peak time were more affected by CP than were the level ones of mesor (time series mean) and amplitude of variation. This observation may indicate the involvement of independent pathways of action upon each of the rhythm parameter sets. As a result, the rhythm phenotype of each function was modified and novel timing relationships were shaped. The results show that the circadian systems of BALBc and c57Bl6J mice failed to re-entrain after cessation of CP injections (tested on the first day following the 10 d course of CP administration), pointing to a direct effect of the medication on the tissues. The findings imply that optimal chemotherapeutic protocols should be tailored individually, according to the current temporal order rather than administered at a fixed predetermined circadian time. Further studies are necessary to determine which variables and rhythmic parameters could be useful to determine the optimal timing of chronochemotherapy.
AB - The competence to preserve the optimal timing relationships between rhythmic variables enables adaptation of mammals to alternate environmental conditions. The capability to re-entrain depends on genetic factors and the nature of imposed time cues. In the present study, the authors examined in rodent models, following a cancer chronochemotherapy, cisplatin (CP), the rhythm patterns of locomotor activity and of a few biochemical variables (alkaline phosphatase and creatinine phosphokinase in kidney tissue and plasma, kidney urea nitrogen, and white blood cell count). Males of two inbred mice strains, BALBc and c57Bl6J, received 10 consecutive daily intraperitoneal (i.p.) injections of either saline or CP at zeitgeber time 22 (ZT22). CP administration altered the rhythms of each examined function in both strains. The type and extent of the changes varied among variables, tissuesplasma, and mouse strain. Yet, the effect of CP was not detected on all parameters, but only in ∼60 of them. In addition, in the majority of the studied parameters, BALBc and c57Bl6J mice differed in their response to CP. The temporal parameters of period and peak time were more affected by CP than were the level ones of mesor (time series mean) and amplitude of variation. This observation may indicate the involvement of independent pathways of action upon each of the rhythm parameter sets. As a result, the rhythm phenotype of each function was modified and novel timing relationships were shaped. The results show that the circadian systems of BALBc and c57Bl6J mice failed to re-entrain after cessation of CP injections (tested on the first day following the 10 d course of CP administration), pointing to a direct effect of the medication on the tissues. The findings imply that optimal chemotherapeutic protocols should be tailored individually, according to the current temporal order rather than administered at a fixed predetermined circadian time. Further studies are necessary to determine which variables and rhythmic parameters could be useful to determine the optimal timing of chronochemotherapy.
KW - Circadian disruption
KW - Circadian rhythm
KW - Cisplatin
KW - Genetic influences
KW - Inbred strain
KW - Mice
KW - Re-entrainment
UR - http://www.scopus.com/inward/record.url?scp=84863188356&partnerID=8YFLogxK
U2 - 10.3109/07420528.2012.685137
DO - 10.3109/07420528.2012.685137
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AN - SCOPUS:84863188356
SN - 0742-0528
VL - 29
SP - 724
EP - 735
JO - Chronobiology International
JF - Chronobiology International
IS - 6
ER -