{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T07:49:20Z","timestamp":1717746560167},"reference-count":53,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The protective effect of melatonin against phenobarbital-induced oxidative stress in the rat liver was measured based on lipid peroxidation levels (malondialedyde and 4-hydroxyalkenals). Cellular proliferation, DNA synthesis and cell cycle duration were quantitated by the incorporation of 3H-thymidine, detected by autoradiography, into newly synthesized DNA. Two experiments were carried out in this study, each on four equal-sized groups of male rats (control, melatonin [10 mg\/kg], phenobabital [20 mg\/kg] and phenobarbital plus melatonin). Experiment I was designed to study the proliferative activity and rate of DNA synthesis, and measure the levels of lipid peroxidation, while experiment II was for cell cycle time determination. Relative to the controls, the phenobarbital-treated rats showed a significant increase (P &lt; 0.01) in the lipid peroxidation levels (30.7%), labelling index (69.4%) and rate of DNA synthesis (37.8%), and a decrease in the cell cycle time. Administering melatonin to the phenobarbital-treated rats significantly reduced (P &lt; 0.01) the lipid peroxidation levels (23.5%), labelling index (38.2%) and rate of DNA synthesis (29.0%), and increased the cell cycle time. These results seem to indicate that the stimulatory effect of phenobarbital on the oxidized lipids, proliferative activity, kinetics of DNA synthesis and cell cycle time alteration in the liver may be one of the mechanisms by which the non-genotoxic mitogen induces its carcinogenic action. Furthermore, melatonin displayed powerful protection against the toxic effect of phenobarbital.<\/jats:p>","DOI":"10.2478\/s11658-007-0005-2","type":"journal-article","created":{"date-parts":[[2007,2,12]],"date-time":"2007-02-12T08:02:05Z","timestamp":1171267325000},"source":"Crossref","is-referenced-by-count":4,"title":["An autoradiographic study of cellular proliferaton, DNA synthesis and cell cycle variability in the rat liver caused by phenobarbital-induced oxidative stress: The protective role of melatonin"],"prefix":"10.2478","volume":"12","author":[{"given":"Gamal","family":"El-Sokkary","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","reference":[{"key":"ref81","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/0378-4274(95)03550-8","article-title":"Role of active cell death apoptosis in multi - stage carcinogenesis Toxicol http dx doi org","volume":"9","author":"Schulte","year":"1995","journal-title":"Lett"},{"key":"ref281","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.tox.2005.05.003","article-title":"Melatonin protects against lead - induced hepatic and renal toxicity in male rats http dx doi org","volume":"29","author":"El","year":"2005","journal-title":"Toxicology"},{"key":"ref371","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1093\/carcin\/23.2.341","article-title":"Formation of - hydroxydeoxyguanosine and cell - cycle arrest in the rat liver via generation of oxidative stress by phenobarbital : association with expression profiles of p cyclin and http dx doi org","volume":"38","author":"Kinoshita","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref361","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/0304-3835(93)90074-J","article-title":"Effect of regeneration and hyperplasia on levels of DNA base oxidation in rat liver http dx doi org","volume":"37","author":"Murkofsky","year":"1993","journal-title":"Cancer Lett"},{"key":"ref431","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1093\/carcin\/19.7.1173","article-title":"Attenuation of checkpoint function by the non - genotoxic carcinogen Phenobarbital http dx doi org","volume":"44","author":"Gonzales","year":"1998","journal-title":"Carcinogenesis"},{"key":"ref481","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/0092-8674(92)90586-2","article-title":"Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells http dx doi org","volume":"49","author":"Hartwell","year":"1992","journal-title":"Cell"},{"key":"ref511","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1034\/j.1600-079x.2002.10820.x","article-title":"A multifactorial approach employing melatonin to accelerate resynchronization of sleep - wake cycle after a timezone westerly transmeridian flight in elite soccer athletes http dx doi org","volume":"52","author":"Cardinali","year":"2002","journal-title":"Pineal Res"},{"key":"ref101","first-page":"415","article-title":"Liver carcinogenesis is not a predicted outcome of chemically induced hepatocyte proliferation Toxicol Indust","volume":"11","author":"Melnick","year":"1993","journal-title":"Health"},{"key":"ref271","first-page":"215","article-title":"Melatonin supplementation restores cellular proliferation and DNA synthesis in the splenic and thymic lymphocytes of old rats Neuroendocrinol","volume":"28","author":"El","year":"2003","journal-title":"Lett"},{"key":"ref341","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1093\/carcin\/15.9.1917","article-title":"Modulation of phenobarbitone induced loss of gap junctional intercellular communication in hepatocyte couplets http dx doi org","volume":"35","author":"Guppy","year":"1994","journal-title":"Carcinogenesis"},{"key":"ref411","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/0041-008X(90)90196-2","article-title":"Induction of urinary bladder of the rat Toxicol http dx doi org","volume":"42","author":"Debiec","year":"1990","journal-title":"Appl Pharmacol"},{"key":"ref251","first-page":"461","article-title":"Melatonin protects against oxidative stress induced by the kidney arcinogen KBrO Neuroendocrinol","volume":"26","author":"El","year":"2000","journal-title":"Lett"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/0147-6513(78)90014-3","article-title":"Is Phenobarbital carcinogenic ? 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