Abstract:
:Oltipraz, developed as an antischistosomal agent, protects against the hepatotoxicity of many xenobiotics and is known to be an effective inhibitor of experimental carcinogenesis in rodents. In the present study, we investigated its effects on the development of lesions in LEC rats, established as a mutant strain characterized by a hereditary predisposition for hepatic damage with severe jaundice. A total of 35 male 6-week-old LEC rats were divided into 2 groups, one administered diet supplemented with oltipraz at a dose of 400 ppm, and the other fed basal diet alone. Animals in each group were sequentially sacrificed at 10, 15, and 25 weeks after commencement of the oltipraz administration. Eight animals died or became moribund in the oltipraz group during weeks 10 and 11 of the treatment, whereas only one rat in the nontreatment group died after 16 weeks. All dead or moribund animals showed severe or moderate jaundice. The treatment caused a decrease in body weight gain from 9 to 13 weeks, and an increase in relative liver weight at each sacrifice point. Serum biochemical assays performed at week 25 revealed elevated levels of serum AST, ALT, LDH, ALP, gamma-GTP, and Cu in the treated-animals. The glutathione level in the livers of oltipraz-treated animals was significantly higher than that in the control rats. Histopathologically, enlarged hepatocytes with large nuclei, focal necrosis, pigment granule-laden Kupffer cells and hypertrophy of renal tubule cells were observed in both groups, but the severity of these changes was greater in the oltipraz group. Our results thus indicate that spontaneous hepatic damage in LEC rats is enhanced by oltipraz, by a mechanism that remains to be elucidated.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Nakamura H,Nishikawa A,Furukawa F,Kasahara K,Miyauchi M,Okazaki K,Imazawa T,Uchida K,Hirose Mdoi
10.1080/019262302753559506subject
Has Abstractpub_date
2002-03-01 00:00:00pages
173-7issue
2eissn
0192-6233issn
1533-1601journal_volume
30pub_type
杂志文章abstract::We believe the development and validation of in vitro alternatives to eliminate the need to use animals in ocular irritation testing must be based on a thorough understanding of the mechanisms of ocular irritation. We have recently undertaken the task of developing such an understanding for a panel of surfactants. The...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600206
更新日期:1998-03-01 00:00:00
abstract::Microcystin-LR (MCLR) is an acute hepatotoxicant and suspected carcinogen. Previous chronic studies have individually described hepatic morphologic changes, or alterations in the cytoskeleton, cell signaling or redox pathways. The objective of this study was to characterize chronic effects of MCLR in wild-type mice ut...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230701383210
更新日期:2007-06-01 00:00:00
abstract::One application of genomics in drug safety assessment is the identification of biomarkers to predict compound toxicity before it is detected using traditional approaches, such as histopathology. However, many genomic approaches have failed to demonstrate superiority to traditional methods, have not been appropriately ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500321213
更新日期:2005-01-01 00:00:00
abstract::Progressive renal interstitial fibrosis occurs following tissue injury, resulting in chronic renal failure. In the fibrogenesis, macrophages are speculated to induce myofibroblasts producing matrix protein. The kinetics of these cells in renal fibrosis induced in rats by repeated injection of cisplatin (CDDP) (2 mg/kg...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339602400208
更新日期:1996-03-01 00:00:00
abstract::Results of early nonclinical "General Toxicology" studies are used to set a safe starting dose for first-in-human (FIH) clinical trials. In FIH trials, the research subjects are typically healthy volunteers who have little to gain but much to lose if a trial goes wrong. With that in mind, good laboratory practice regu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313506878
更新日期:2014-01-01 00:00:00
abstract::Some developmental dual-acting PPARalpha/gamma agonists, such as ragaglitazar, have shown carcinogenic effects in the rodent urinary bladder urothelium after months-years of dosing. We examined early (precancerous) changes in the bladder urothelium of rats orally dosed with ragaglitazar, using a newly developed flow c...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230500214657
更新日期:2005-01-01 00:00:00
abstract::The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which re...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339702500306
更新日期:1997-05-01 00:00:00
abstract::Phosphatidylinositol 3-kinases (PI3Ks) regulate intracellular signaling events for multiple cell surface receptors. Phosphatidylinositol 3-kinase δ, 1 of 4 class I PI3K isoforms, is primarily found in leukocytes and regulates immune cell functions. Here, we report changes in the immune and digestive systems that were ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320966238
更新日期:2020-12-01 00:00:00
abstract::In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrach...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200118
更新日期:1984-01-01 00:00:00
abstract::Changes in p53 expression, apoptosis and cell proliferation after treatment with 4-hydroxyaminoquinoline 1-oxide (4HAQO) were investigated in the rat pancreas and liver, target and nontarget organs for tumorigenesis, respectively. Male rats were given a single intravenous injection of 4HAQO at a dose of 20 mg/kg body ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230390241855
更新日期:2003-11-01 00:00:00
abstract::Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant tox...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339502300209
更新日期:1995-03-01 00:00:00
abstract::In the present study, susceptibility of CB6F1 mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and p53 gene knockout mice (p53 (+/-) mice) to urethane-induced lung carcinogenesis was compared under the same experimental conditions. Both strains were administered 500 ppm urethane in their drinking water for...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230590908231
更新日期:2005-01-01 00:00:00
abstract::Cardiac troponin (cTn) is a sensitive and specific biomarker for assessing cardiac damage and should be utilized in drug safety assessment. Lactate dehydrogenase and creatine kinase isoenzyme analyses have historically been used in pre-clinical toxicity testing to assess cardiac injury, but since these assays are less...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310382438
更新日期:2010-12-01 00:00:00
abstract::Most available data on the involvement of p53 in rodent carcinogenesis are based on results of the end point of chemically or virally induced carcinogenesis, i.e., tumors. To investigate the role of altered p53 expression in early stages of rodent hepatocarcinogenesis in a systematic way, we treated male Wistar rats f...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600507
更新日期:1998-09-01 00:00:00
abstract::Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to deter...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623312464122
更新日期:2013-01-01 00:00:00
abstract::More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623307310946
更新日期:2008-01-01 00:00:00
abstract::The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623316642527
更新日期:2016-08-01 00:00:00
abstract::A review of the data obtained from various studies on carcinogenicity of vinyl chloride (VC) in rodents, particularly on the effect of dose, age, duration of exposure and potential reversibility of lesions, revealed that vinyl chloride-induced carcinogenicity in rodents was dose and time related; no recovery occurred ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338301100210
更新日期:1983-01-01 00:00:00
abstract::A compendium of carcinogenesis bioassay results organized by target organ is presented for 738 chemicals that are carcinogenic in chronic-exposure, long-term bioassays in at least 1 species. This compendium is based primarily on experiments in rats or mice; results in hamsters, monkeys, and dogs are also reported. The...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/019262301753385979
更新日期:2001-11-01 00:00:00
abstract::Livers of male Sprague-Dawley rats were evaluated for foci and nodules 90 days and 16 months after one or two oral doses of 1,2-dibromoethane (DBE). Rats (190 g) were given the following oral treatments. Controls received corn oil (2.5 ml/kg) at 0 and 24 hr. DBE X 1 received corn oil at 0 hr and 75 mg DBE/kg at 24 hr....
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338401200402
更新日期:1984-01-01 00:00:00
abstract::Mouse renal cell tumors (RCTs) were induced in male CBA mice by 5 subcutaneous injections of 8 mg 1,2-dimethylhydrazine (DMH)/kg body weight once a week. After a lag period of 2 yr kidneys were removed, and serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glycogen con...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339402200407
更新日期:1994-07-01 00:00:00
abstract::The development process of myelination varies between region and species. Fully myelinated fibers are required if mammalian neural circuits are to function normally. Histology samples at staggered time points throughout the study were examined at days 4, 5, 7, 8, 10, 14, 17, 24, 37, and 44. We suggest that the develop...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313503518
更新日期:2014-07-01 00:00:00
abstract::Weber, K. (2017). Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats. J Toxicol Pathol45, 64-75. (Original DOI: 10.1177/0192623316672075) In the January 2017 issue of Toxicologic Pathology, a number of in text Table citations were incorrectly labeled. The following are the sentences ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,已发布勘误
doi:10.1177/0192623317702643
更新日期:2017-04-01 00:00:00
abstract::Substantial progress in understanding nongenotoxic or secondary mechanisms of tumorigenesis has been made over the past decade. However, the methods used in regulated studies for assessment of carcinogenic potential in chemicals in development have not evolved significantly. Based on the experience of over 30 yr of te...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262339602400610
更新日期:1996-11-01 00:00:00
abstract::This overview briefly summarizes the cellular pathobiology of experimental atherosclerosis and is then followed by a consideration of how 3 major risk factors interact with the hypothesized pathogenetic process. First, since hemodynamics and blood flow influence the localization of atherosclerotic plaques, possible me...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract::To investigate pathogenesis of post-bile duct (BD) injury fibrosis, interlobular BD epithelial injury was induced in male F344 rats by a single IP injection of α-naphthylisothiocyanate (75 mg/kg body weight) and rats were observed for 12 days. On days 1 to 2, cholangiocytes were injured and desquamated. On days 3 to 5...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623311413790
更新日期:2011-08-01 00:00:00
abstract::Laser scanning cytometry (LSC) is a powerful tool for qualitative and quantitative analysis of tissue sections in preclinical drug development. LSC combines the strengths of flow cytometry with tissue architecture retention. This technology has been used predominantly with immunofluorescent techniques on cell culture ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623307312704
更新日期:2008-01-01 00:00:00
abstract::A total of 75 BALB/cStCrlfC3H/Nctr male weanling mice were administered either 0 or 250 ppm of 4 ethylsulfonylnaphthalene-1-sulfonamide (ENS) in the diet for periods up to 14 days to evaluate the early morphological changes of the transitional epithelium of the urinary bladder with scanning (SEM) and transmission (TEM...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400302
更新日期:1986-01-01 00:00:00
abstract::Standard histology trimming practices for toxicity studies in dogs include preparation of a section of the papillary muscle associated with the left ventricular free wall-the anteriolateral or anterior muscle. In contrast, the posteromedial or posterior papillary muscle, associated with the interventricular septum, is...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320963020
更新日期:2020-10-01 00:00:00
abstract::Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3F1 mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89.1%), mononuclear cell leukemia (5...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339802600318
更新日期:1998-05-01 00:00:00