Year : 2015 | Volume
: 5 | Issue : 4 | Page : 117-
A research milieu calls for attention: Biological clock in health and disease
Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India
Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu
|How to cite this article:|
Subramanian P. A research milieu calls for attention: Biological clock in health and disease.Int J Nutr Pharmacol Neurol Dis 2015;5:117-117
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Subramanian P. A research milieu calls for attention: Biological clock in health and disease. Int J Nutr Pharmacol Neurol Dis [serial online] 2015 [cited 2021 Oct 26 ];5:117-117
Available from: https://www.ijnpnd.com/text.asp?2015/5/4/117/167504
Chronobiology is the branch of science that deals with the study of temporal organization of living organisms (biological rhythms) and its underlying mechanisms. Large numbers of evidences have been provided for the rhythmic, humdrum-in-time distinctions in the influences, and/or pharmacokinetics of mammals and humans. Adverse drug reactions as a function of biological rhythms have been observed. Lot of research works emphasized that disturbances in the suprachiasmatic nuclei (SCN) ("the biological clock" located in the anterior hypothalamus) function promote hypertension, cancer, diabetes, sleep disorders, and Parkinson's and Alzheimer's diseases to cite a few.
Molecular circadian clocks are crucial for the appropriate orchestration of the cell proliferation. DNA replication would be aptly suited to the dark hours when DNA cannot be rendered to the detrimental ultraviolet (UV) radiation. Wee1, an indispensable factor functioning at the G2/M transition, is also a circadian clock gene in the liver. Wee1 is expressed inphase with mPer1 in the liver and displays high amplitude and stout oscillations. Regulation of its transcription is interceded by the CLOCK/BMAL1 complexes in the 5' region of Wee1. Abnormal and uncontrolled cell proliferation was observed in mPer2 (circadian clock gene) mutant mice. It was reported that since in hospitals women nurses are exposed to light during the night hours, their melatonin rhythm is suppressed and estrogen production is elevated, thereby leading to an enhanced proliferation of the mammary gland cells and higher incidences of breast cancer. The circadian system on cell cycle and the apoptotic pathways influence tumor growth. Circadian oscillations can be used as marker rhythms for tumor growth, as rhythm deformities raise along with tumor progression. Administration of drugs at defined circadian phases has attained the most excellent antitumor activity.
Chronotherapy refers to the chronopharmacologic approaches to clinical treatment in order to enhance both efficacy and lenience of a drug by establishing the most excellent biological time for its dosing. Circadian changes in the effects of numerous drugs have been documented like sodium salicylate, halothane, prostaglandin F2α, reserpine, cyproheptadine, ethanol, insulin, chlorothiazide, oxymetholone, orciprenaline, indomethacin, lignocaine, and various synthetic corticosteroids. Further, the drugs for which daily variations in their effects were reported in clinical studies are the following: acebutolol, theophylline, atenolol, aminophylline, bevantolol, terbutaline, bisoprolol, methacholine, oxprenolol, dexamethasone, carvedilol, isoprenaline, midodrine, nifedipine, diazepam, verapamil, haloperidol, isradipine, phenylpropanolamine, caffeine, cisplatin, clomipramine, oxaliplatin, folinic acid, terbutaline, doxorubicin, timolol, busulfan, methotrexate, etc.
There is a vast amount of evidences provided at the molecular level that links the metabolic and circadian clock genes and their roles in obesity and other disorders. Despite these vast amounts of evidences, considerably low interest has been paid by young researchers in India and in other parts of Asian countries. Lacking investigations in this area will hinder our understanding of the complete nature of all the diseases. Hence, adequate importance in the research milieau of "choronobiology in health and disease" is the need of the hour.