Circadian rhythms of plasma corticosterone at different times after induction of diabetes. Responses to corticoadrenal stimulation in light and dark phases

Velasco, Ángela; Huerta, Ismael; G-Granda, Teresa; Cachero, Teresa G.; Menéndez, Emma; Marín, B

doi:10.1016/0024-3205(93)90532-8

Cited by 11 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous studies have shown that blood corticosterone levels have a profound effect on the toxicity of MTX in the rat. If the endogenous production of corticosterone is suppressed by dexamethasone treatment, the toxicity of MTX is markedly increased independent of its administration time (English et al 1987;Velasco et al 1993). Our results were similar with this study.…”

Section: Discussionsupporting

confidence: 92%

“…Control and SIDM rats were assigned to two subgroups randomly (each group containing 5 -8 rats). While one of the subgroups was pre-treated with dexamethasone (100 mg/kg, IV) to inhibit endogen corticosteroids (English et al 1987;Velasco et al, 1993;Courtois et al 1999), one hour before the administration of MTX, the other group received only MTX. Polyethylene catheters (0.58 mm ID, Portex Ltd., Kent, UK) were inserted into the jugular vein of each rat for drug administration.…”

Section: Experimental Studymentioning

confidence: 99%

See 1 more Smart Citation

The role of circadian rhythm on the pharmacokinetic of methotrexate in streptozotocin-induced diabetes mellitus rats

Gümüştekin

Kalkan²,

Murat³

et al. 2005

Biological Rhythm Research

View full text Add to dashboard Cite

Chronopharmacokinetic studies have been conducted both in animals and humans. Anticancer agents are of great interest due to their narrow therapeutic range and large pharmacokinetic variability. It was reported that the pharmacokinetics of MTX showed a circadian rhythm in rats and humans. Since diabetes-induced physiological changes can affect pharmacokinetics of drugs, it was reported that MTX blood concentration in diabetic rats was higher than that of the control groups. The present study was designed to elucidate whether these diabetes-induced changes in pharmacokinetics occurred during the day and thus administered MTX at four different times in streptozotocin-induced diabetes mellitus (SIDM) rats. Blood samples were drawn at 5, 15, 30, and 60 min after IV infusion of MTX in both the SIDM and control groups. Control and SIDM Area under the concentration -time curve (AUC) values showed a significant circadian rhythm with a peak located in mid-dark phase at 14:00. Clearance values were significantly low at 14:00 in the diabetic group when compared to other periods and the control group. The MTX AUC was increased when treatment with dexamethasone was given to suppress the endogenous production of corticosterone in both control and SIDM rats. These results suggest that the extent of MTX pharmacokinetics varies with the time of day in the SIDM rats and these variations might be related to changes in corticosterone concentrations.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Experimental Studymentioning

confidence: 99%

The role of circadian rhythm on the pharmacokinetic of methotrexate in streptozotocin-induced diabetes mellitus rats

Gümüştekin

Kalkan²,

Murat³

et al. 2005

Biological Rhythm Research

View full text Add to dashboard Cite

show abstract

“…Not only the average corticosterone level but also the circadian corticosterone rhythmicity can be disturbed in the 15-day DM rat (23,43). The lack of AVP had no effect on CRH mRNA in PVN, POMC mRNA in AL, or morning corticosterone elevation in DM-induced chronic stress, which suggests that AVP does not play a crucial role in HPA axis regulation during DM-chronic stress.…”

Section: Discussionmentioning

confidence: 83%

Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats

Zelena¹,

Filaretova²,

Mergl³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Zelena, Dóra, Ludmila Filaretova, Zsuzsa Mergl, István Barna, Zsuzsanna E. Tóth, and Gábor B. Makara. Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats. Am J Physiol Endocrinol Metab 290: E243-E250, 2006. First published September 6, 2005 doi:10.1152/ajpendo.00118.2005.-Diabetes mellitus (DM), as chronic stress activates the hypothalamopituitary-adrenocortical axis. We examined whether arginine vasopressin (AVP) and the hypothalamic paraventricular nucleus (PVN) participate in DM-induced chronic stress symptoms. AVP-deficient Brattleboro or PVN-lesioned Wistar rats were used with heterozygous or sham-operated controls. The rats were studied 2 wk after a single injection of streptozotocin. The appearance of DM (enhanced water consumption and blood glucose elevation) and the chronic stress-like somatic changes (body weight decrease, thymus involution, adrenal gland hypertrophy) were not influenced by the lack of AVP. By contrast, PVN lesion significantly attenuated DM-induced thymus involution and adrenal gland hypertrophy as well as the increase in water consumption. The corticotropin-releasing hormone mRNA in PVN was diminished by DM and elevated by the lack of AVP without interaction. DM elevated the proopiomelanocortin (POMC) mRNA in the anterior lobe of the pituitary. The lack of AVP had no effect, whereas lesioning the PVN significantly diminished the elevation. The elevated basal corticosterone plasma levels detectable in DM were influenced neither by the lack of AVP nor by lesioning the PVN. Thus the lack of AVP had no influence on DM-induced chronic stress symptoms, but lesioning the PVN attenuated part of them. However, the lack of elevation in POMC mRNA after PVN lesion, together with the maintained corticosterone elevation, suggests that direct adrenal gland activation occurs in untreated DM. chronic stress; Brattleboro rats; corticosterone; proopiomelanocortin; corticotropin-releasing hormone; diabetes mellitus; hypothalamopituitary-adrenocortical axis DIABETES MELLITUS (DM) is an endocrine disorder that is quite common in developed countries (17). Inadequate insulin secretion and insulin resistance with inadequate compensatory insulin release are the main reasons for DM development. The use of toxic agents that destroy ␤-cells in the pancreas and lead to insulin deficiency, such as streptozotocin (STZ), produces a model of DM in animals (36). The most frequent symptoms of DM are blood glucose level elevation, polyuria, polydipsia, and weight loss. However, the long-term disorder can cause many other complications, including cardiovascular, cerebrovascular, or renal ones.Long-term DM as a chronic stress may also induce a dysfunction of the hypothalamo-pituitary-adrenocortical (HPA) axis. A tight connection between HPA axis activity and blood glucose regulation is well known (9, 12). The HPA axis is responsible for the production of glucocorticoids, which are important adaptive hormones. Glucocorticoid hormones participate...

show abstract

“…It is reported that pharmacokinetic changes of drugs in diabetic rats and patients (Gwilt et al 1991;Park et al 1996;Kim et al 1998) may result from physiological changes such as gastrointestinal tract disorders, decrease in the protein binding of drugs (Nadai et al 1990;Park et al 1996), and increase in rat liver cytochrome P-450 levels (O'Connor & Feely 1987;Gwilt et al 1991). Diurnal variations in the concentrations of cortisol and glucose may also affect pharmacokinetics of drugs (English et al 1987;Velasco et al 1993;Radziuk & Pye 2002). Methotrexate (MTX) is an antifolate agent used in the treatment of malignencies including leukaemia, non-Hodgkin's lymphoma and solid tumours (Ferrazzini et al 1991;Koren et al 1992;Zhao et al 1998Zhao et al , 1999Zhao et al , 2000Rots et al 1999).…”

Section: Introductionmentioning

confidence: 93%

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

Gümüştekin

Murad

Gidener

2007

Biological Rhythm Research

View full text Add to dashboard Cite

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.

show abstract

Circadian rhythms of plasma corticosterone at different times after induction of diabetes. Responses to corticoadrenal stimulation in light and dark phases

Cited by 11 publications

References 22 publications

The role of circadian rhythm on the pharmacokinetic of methotrexate in streptozotocin-induced diabetes mellitus rats

The role of circadian rhythm on the pharmacokinetic of methotrexate in streptozotocin-induced diabetes mellitus rats

Hypothalamic paraventricular nucleus, but not vasopressin, participates in chronic hyperactivity of the HPA axis in diabetic rats

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

Contact Info

Product

Resources

About