Circadian variation in methotrexate toxicity in streptozotocin-induced diabetes mellitus rats

Gumustekin M., Murad N., Gidener S.

BIOLOGICAL RHYTHM RESEARCH, cilt.38, sa.1, ss.33-41, 2007 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 1
  • Basım Tarihi: 2007
  • Doi Numarası: 10.1080/09291010600832123
  • Dergi Adı: BIOLOGICAL RHYTHM RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.33-41
  • Anahtar Kelimeler: circadian rhythm, phase shift, diabetes mellitus, methotrexate, toxicity, rat, ENDOGENOUS GLUCOSE-PRODUCTION, DIURNAL-VARIATION, PLATELET SURVIVAL, PHARMACOKINETICS, TRANSPORT, DISPOSITION, CHRONOPHARMACOKINETICS, RESISTANCE, CHILDREN, VOLUME
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

The effects of diabetes mellitus and circadian rhythm on pharmacokinetics or pharmacodynamics of drugs have been previously separately reviewed. In our previous study, a circadian rhythm has been described in the pharmacokinetics of MTX in streptozotocin-induced diabetes mellitus (SIDM) rats. The aim of the present study was to investigate the effects of circadian rhythm on the toxicity of MTX in SIDM rats. The hematologic parameters and serum folic acid levels were measured in control and SIDM groups before and after MTX administration to evaluate its toxicity. We observed that circadian rhythm in basal peripheral WBC counts disappeared after MTX administration in the first hour and were phase shifted on the fifth day. Circadian variations were not observed in the other blood cells. One hour after MTX administration, folic acid levels were high in both groups. However, a circadian rhythm was present only in the diabetic group. The alteration in the rhythm of WBC counts in diabetic rats may originate not only from the effect of MTX but also physiological alterations due to diabetes and/or the varying cell cycle entry rates in the hematopoetic stem cells.