Pharmacologic Modulation of Reduced Glutathione Circadian Rhythms with Buthionine Sulfoximine: Relationship with Cisplatin Toxicity in Mice

Li, Xiaomei; Metzger, Gérard; Filipski, Elisabeth; Boughattas, Naceur A.; Lemaigre, G; Hecquet, B; Filipski, Jan; Lévi, Françis

doi:10.1006/taap.1996.8088

Cited by 49 publications

(37 citation statements)

References 26 publications

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“…However, despite the suppression of the circadian pattern in rest-activity, markedly altered yet persistent 24-h changes were documented for plasma corticosterone, circulating leukocyte count, and liver GSH in the SCN-lesioned mice in our study. Moreover, in these animals, DPD transcription in liver and cell cycle phase distribution in bone marrow remained rhythmic along the 24-h time scale, with temporal patterns similar to those found in sham-operated mice or reported in healthy controls (4,19,28,40,46). The rhythms were statistically validated with both ANOVA and cosinor analysis.…”

Section: Discussionsupporting

confidence: 77%

“…We selected cell cycle phase distribution in bone marrow and dihydropyrimidine dehydrogenase (DPD) mRNA expression in liver as determinants of 5-fluorouracil tolerability (17,40,45,51) and reduced glutathione (GSH) in liver as a determinant of platinum complex tolerability (4,6,7,28).…”

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confidence: 99%

“…In the current study, we examined the effects of SCN ablation on rhythms in cellular detoxication processes and cell cycle-related events known as critical determinants for the dosing time dependency of anticancer drugs tolerability (5,19,26,28,35,40,46,51). We selected cell cycle phase distribution in bone marrow and dihydropyrimidine dehydrogenase (DPD) mRNA expression in liver as determinants of 5-fluorouracil tolerability (17,40,45,51) and reduced glutathione (GSH) in liver as a determinant of platinum complex tolerability (4,6,7,28).…”

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confidence: 99%

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Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Filipski

King²,

Etienne³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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. Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice. Am J Physiol Regul Integr Comp Physiol 287: R844 -R851, 2004. First published June 24, 2004 10.1152/ajpregu. 00085.2004.-Rest-activity or cortisol rhythms can be altered in cancer patients, a condition that may impair the benefits from a timed delivery of anticancer treatments. In rodents, the circadian pattern in rest-activity is suppressed by the destruction of the suprachiasmatic nuclei (SCN) in the hypothalamus. We sought whether such ablation would result in a similar alteration of cellular rhythms known to be relevant for anticancer drug chronopharmacology. The SCN of 77 B6D2F1 mice synchronized with 12 h of light and 12 h of darkness were destroyed by electrocoagulation [SCN(Ϫ)], while 34 animals were sham operated. Activity and body temperature were recorded by telemetry. Blood and organs were sampled at one of six circadian times for determinations of serum corticosterone concentration, blood leukocyte count, reduced glutathione (GSH), and dihydropyrimidine dehydrogenase (DPD) mRNA expression in liver and cell cycle phase distribution of bone marrow cells. Sham-operated mice displayed significant 24-h rhythms in rest-activity and body temperature, whereas such rhythms were found in none and in 15% of the SCN(Ϫ) mice, respectively. SCN lesions markedly altered the rhythmic patterns in serum corticosterone and liver GSH, which became nonsinusoidal. Liver DPD mRNA expression and bone marrow cell cycle phase distribution displayed similar 24-h sinusoidal patterns in shamoperated and SCN(Ϫ) mice. These results support the existence of another light-dark entrainable pacemaker that can coordinate cellular functions in peripheral organs. They suggest that the delivery of anticancer treatments at an optimal time of day may still be beneficial, despite suppressed rest-activity or cortisol rhythms. circadian coordination; cancer chronotherapeutics; cortisol; cell cycle; dihydropyrimidine dehydrogenase APPROXIMATELY 25% of cancer patients displayed profound alterations of rest-activity pattern and cortisol rhythm independently of tumor stage or general condition (32-34). Poorer tumor response and shorter survival were reported in these patients compared with those with near normal circadian function (36,43). Such altered circadian function could also impair the therapeutic benefit that can result from chronotherapeutics, i.e., the delivery of anticancer treatments at selected times of day (12,23,26,27).This treatment optimization method is based on the regulation of cellular metabolism and proliferation by a molecular clock. This clock consists of interconnected molecular loops involving up to 12 specific clock genes. It has been uncovered in most mammalian tissues (21,35,41,42) and rhythmically regulates the transcription of 5-10% of the genome (14,21,41,42). Indeed, sustained rhythms in transcription or other cellular functions have been demonstrated in cultured mammalian cells, giving rise to the con...

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Section: Discussionsupporting

confidence: 77%

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confidence: 99%

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confidence: 99%

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Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Filipski

King²,

Etienne³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Similar circadian patterns have been shown for the chronopharmacology of anticancer drugs across different rodent species or strains . Mechanisms include rhythms in reduced glutathione content in liver and other organs and host tolerability for platinum complexes in rats and mice (Bélanger et al, 1988;Li et al, 1997) and rhythms in BCL-2 expression in bone marrow and host tolerability for docetaxel in B6D2F 1 and C3H/He mice (Tampellini et al, 1998;Granda et al, 2001Granda et al, , 2005. A similar circadian pattern in the anticancer efficacy of the same drug has also been shown in different experimental tumour models .…”

Section: Discussionmentioning

confidence: 84%

Preclinical relevance of dosing time for the therapeutic index of gemcitabine–cisplatin

Tanaka

Sun

et al. 2005

Br J Cancer

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The relevance of gemcitabine timing for chronotherapeutic optimisation was investigated. Healthy mice received multiple doses of gemcitabine (120, 160 or 200 mg kg À1 injection (inj) À1 ) at one of six circadian times (3, 7, 11, 15, 19 or 23 h after light onset -HALO) on days 1, 4, 7 and 10 or a single dose of gemcitabine (400 mg kg À1 ) at 11 or 23 HALO7cisplatin (5 mg kg À1 at 1 min, 4 or 8 h later). Mice bearing Glasgow osteosarcoma received multiple doses of gemcitabine (200 mg kg À1 inj À1 ) at 11 or 23 HALO7cisplatin (5 mg kg À1 inj À1 at 1 min or 4 h later) on days of 10, 13, 16 and 19 following tumour inoculation. A circadian rhythm in body weight loss was statistically validated, with 1030 HALO corresponding to the least toxic time (95% CL, 0800 to 1300). Gemcitabine dosing produced least body weight loss and least neutropenia after injection at 11 vs 23 HALO, whether the drug was given alone or with cisplatin (P ¼ 0.001). Gemcitabine -cisplatin tolerability was improved by dosing gemcitabine at 11 HALO and CDDP at 15 HALO (Po0.001). The administration of this schedule to tumour-bearing mice increased median survival three-fold as compared to treatments where both drugs were given simultaneously at 11 or 23 HALO (P ¼ 0.02). The optimal schedule would correspond to the delivery of gemcitabine upon awakening and cisplatin near mid-activity in cancer patients.

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“…The explanation of the mechanisms by which chronotherapeutics works seem to involve both chronopharmacokinetic and chronopharmacodynamic components. For instance, oxaliplatin PK has been shown to have circadian rhythmicity [35,169], and this may be related to circadian rhythms in circulating or cellular compounds, mainly reduced glutathione, binding this molecule [174,175]. More generally, circadian rhythms in the activity of different drug processing enzymes, such as dihydropyrimidine dehydrogenase (DPD) for 5-fluorouracil [19], have been found, explaining circadian effects in terms of chronopharmacokinetics.…”

Section: Chronotherapeutics: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Modelling Physiological and Pharmacological Control on Cell Proliferation to Optimise Cancer Treatments

Clairambault

2009

Math. Model. Nat. Phenom.

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Abstract. This review aims at presenting a synoptic, if not exhaustive, point of view on some of the problems encountered by biologists and physicians who deal with natural cell proliferation and disruptions of its physiological control in cancer disease. It also aims at suggesting how mathematicians are naturally challenged by these questions and how they might help, not only biologists to deal theoretically with biological complexity, but also physicians to optimise therapeutics, on which last point the focus will be set here. To this purpose, mathematical modelling should represent proliferating cell population dynamics with natural built-in control targets (which implies modelling the cell division cycle), together with the distribution of drugs in the organism and their molecular actions on different targets at the cell level on proliferation, i.e., molecular pharmacokinetics-pharmacodynamics of antiproliferative drugs. This should make possible optimal control of drug delivery with constraints to be determined according to the main pharmacological issues encountered in the clinic: unwanted toxic side-effects, occurrence of drug resistance. Mathematical modelling should also take into account physiological determinants of cell and tissue proliferation, such as intervention of the immune system, circadian control on cell cycle checkpoint proteins, and activity of intracellular drug processing enzymes together with individual variations in the activities of these proteins (genetic polymorphism). Taking these points into account will add to the rich scenery of normal or disrupted cell and tissue regulations, and their corrections by drugs, a natural environmental, whole body physiological, frame. It is necessary indeed to consider such a framework if one wants to eventually be actually helpful to clinicians who routinely treat by combinations of drugs living Humans with their complex whole body regulations, often dependent on genotypic variations, and not isolated cells or tissues.Key words: cell proliferation, population dynamics, physiologically structured partial differential equations, pharmacological control, pharmacokinetics-pharmacodynamics, physiological modelling, cancer treatments, therapeutic optimisation, individualised medicine AMS subject classification: 92-02, 92B05 Biological common knowledge on cancerThis section shortly presents the general scenery of cancer evolution and features that must be included in models designed to describe and control it, bearing in mind a more descriptive (physicist's) than a therapeutic (physician's) point of view, only to reverse this perspective in the following sections, in which will be stressed the interest of modelling from the point of view of control, at least if one wants to design models for therapeutic applications. This biological section will be only a short sketch, if one considers that on this subject many books have already been written, e.g. [24,78,96,97,223]. Cancer: a challenging public health problemCardiovascular diseases and cancer are by fa...

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Pharmacologic Modulation of Reduced Glutathione Circadian Rhythms with Buthionine Sulfoximine: Relationship with Cisplatin Toxicity in Mice

Cited by 49 publications

References 26 publications

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Preclinical relevance of dosing time for the therapeutic index of gemcitabine–cisplatin

Modelling Physiological and Pharmacological Control on Cell Proliferation to Optimise Cancer Treatments

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