{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:06:41Z","timestamp":1777914401774,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[1989,4,1]],"date-time":"1989-04-01T00:00:00Z","timestamp":607392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[1989,4]]},"abstract":"\n CCl\n 4<\/jats:sub>\n is a hepatotoxic haloalkane, capable of producing hepatocellular fatty degeneration and centrilobular necrosis. Previous reports indicate induction of liver regeneration after 36-48 hr of CCl\n 4<\/jats:sub>\n treatment, which is considered as a secondary effect. The present investigation was undertaken to evaluate the primary effects of CCl\n 4<\/jats:sub>\n on hepatic DNA synthesis and to correlate liver regeneration with CCl\n 4<\/jats:sub>\n toxicity. These studies were conducted in normal and actively regenerating livers using male Sprague-Dawley rats undergoing sham operation (SH), or partial (70%) hepatectomy (PH). Incorporation of\n 3<\/jats:sup>\n H-thymidine (\n 3<\/jats:sup>\n H-T) in hepatocellular nuclear DNA and autoradiographic analyses of liver sections served as indices for hepatocellular regeneration. Initial experiments established that peak regeneration occurs at 2 days post-PH (PH\n 2<\/jats:sub>\n ) and liver regeneration phases out by 7 days post-PH (PH\n 7<\/jats:sub>\n ). SH and PH rats were challenged with a single ip dose of either corn oil vehicle or CCl\n 4<\/jats:sub>\n at either 0.1 ml\/kg (to represent subtoxic dose) or 2.5 ml\/kg (to represent toxic dose). The low dose of CCl\n 4<\/jats:sub>\n was not toxic and did not alter\n 3<\/jats:sup>\n H-T incorporation and percentage labelled cells at 6 or 24 hours after administration to SH, PH\n 2<\/jats:sub>\n or PH\n 7<\/jats:sub>\n groups, indicating that there was no interference with PH-stimulated hepatocellular regeneration. The high dose of CCl\n 4<\/jats:sub>\n was significantly hepatotoxic and lethal in SH rats, while in PH\n 2<\/jats:sub>\n rats both hepatotoxic and lethal effects were significantly decreased.\n 3<\/jats:sup>\n H-T incorporation as well as percentage labelled cells, highly stimulated by PH, were significantly decreased by high dose of CCl\n 4<\/jats:sub>\n . However, hepatocellular regeneration in PH\n 2<\/jats:sub>\n rats treated with high dose of CCl\n 4<\/jats:sub>\n was still significantly higher than SH or PH, groups by virtue of the stronger stimulatory effect of PH. In PH\n 7<\/jats:sub>\n rats, where hepatocellular regeneration had returned to the SH level, the hepatotoxic and lethal effects of the large dose of CCl\n 4<\/jats:sub>\n were also restored. These findings show that the progressive phase of a single high dose of CCl\n 4<\/jats:sub>\n injury which normally culminates in hepatotoxic and lethal effects is significantly mitigated by previously stimulated hepatocellular regeneration. High dose of CCl\n 4<\/jats:sub>\n suppresses hepatocellular regeneration at early time points after administration in contrast to the smaller subtoxic dose of CCl\n 4<\/jats:sub>\n . By virtue of the much stronger stimulatory effect, PH results in the protection against the hepatotoxic and lethal effects of CCl\n 4<\/jats:sub>\n despite the obtunding effects of the high dose on hepatocellular regeneration.\n <\/jats:p>","DOI":"10.1177\/019262338901700304","type":"journal-article","created":{"date-parts":[[2017,1,7]],"date-time":"2017-01-07T02:46:17Z","timestamp":1483757177000},"page":"494-505","source":"Crossref","is-referenced-by-count":68,"title":["Protection of Hepatotoxic and Lethal Effects of CCl by Partial Hepatectomy"],"prefix":"10.1177","volume":"17","author":[{"given":"Prasada Rao S.","family":"Kodavanti","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urmila M.","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Young","sequence":"additional","affiliation":[{"name":"Postdoctoral trainee supported by Training Program in Toxicology NIEHS, ES-07045."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward F.","family":"Meydrech","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi 39216."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harihara M.","family":"Mehendale","sequence":"additional","affiliation":[{"name":"To whom all correspondence should be addressed. Recipient of the 1988 Burroughs Wellcome Toxicology Scholar Award."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[1989,4,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(83)90084-7"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01990017"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00334621"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1016\/0272-0590(86)90260-5"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196709282771306"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.1042\/bj0620315"},{"key":"atypb7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0022-3565(25)26171-7","volume":"134","author":"Butler TC","year":"1961","journal-title":"J. Pharmacol. Exp. 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