Author/Editor		Prosenc-Zmrzljak, Uršula; Rozman, Damjana
Title		Circadian regulation of the hepatic endobiotic and xenobitoic detoxification pathways: the time matters
Type		članek
Source		Chem Res Toxicol
Vol. and No.		Letnik 25, št. 4
Publication year		2012
Volume		str. 811-24
Language		eng
Abstract		Metabolic processes have to be regulated tightly to prevent waste of energy and to ensure sufficient detoxification. Most anabolic processes operate in a timely manner when energy intake is the highest, while catabolism takes place in energy spending periods. Endobiotic and xenobiotic metabolism are therefore under circadian control. Circadian regulation is mediated through the suprachiasmatic nucleus (SCN), a master autonomous oscillator of the brain. Although many peripheral organs have their own oscillators, the SCN is important in orchestrating and entraining organs according to the environmental light cues. However, light is not the only signal for entrainment of internal clocks. For endobiotic and xenobitoic detoxification pathways, the food composition and intake regime are equally important. The rhythm of the liver as an organ where the major metabolic pathways intersect depends on SCN signals, signals from endocrine tissues, and, importantly, the type and time of feeding or xenobiotics ingestion. Several enzymes are involved in detoxification processes. Phase I is composed mainly of cytochromes P450, which are regulated by nuclear receptors. Phase II enzymes modify the phase I metabolites, while phase III includes membrane transporters responsible for the elimination of modified xenobiotics. Phases I-III of drug metabolism are under strong circadian regulation, starting with the drug-sensing nuclear receptors and ending with drug transporters. Disturbed circadian regualtion (jet-lag, shift work, and dysfunction of core clock genes) leads to changed periods of activity, sleep disorders, disturbed glucose homeostasis, breast or colon cancer, and metabolic syndrome. As many xenobiotics influence the circadian rhythm of the liver, bad drug administration timing can worsen the above listed effects. (Abs. trunc. at 2000 ch.)
Descriptors		CIRCADIAN RHYTHM LIVER METABOLIC DETOXICATION, DRUG NAD NADP BLOOD GLUCOSE CHOLESTEROL FATTY ACIDS FOOD, FORTIFIED CHRONOTHERAPY