Abstract:
:Hepatic microsomal enzymes play an important role in thyroid hormone homeostasis. Glucuronidation of thyroxine is the rate limiting step in the biliary excretion of thyroxine in the rat; the monodeiodinases are important in the conversion of T4 to T3 and reverse T3 and subsequent deiodinations. Phenobarbital is known to affect thyroid function in rats due to an alteration of hormone disposition. We have further characterized these effects and have demonstrated that phenobarbital increases the biliary excretion of thyroxine glucuronide primarily as a result of an induction of hepatic thyroxine glucuronyltransferase. Studies on the mode of action for phenobarbital promotion of thyroid follicular neoplasia were conducted using an initiation-promotion model established by Hiasa et al (35). In this model, we demonstrated that supplemental administration of thyroxine blocked the promoting effect of phenobarbital and furthermore, using various dosages of thyroxine, we observed that the tumor promoting effect of phenobarbital was directly proportional to the level of plasma TSH. The results of these studies support the hypothesis that the tumor promoting effect of phenobarbital in the thyroid gland is mediated via increased secretion of pituitary TSH as a compensatory response to the known effects of phenobarbital on peripheral thyroid hormone disposition. Since a number of microsomal enzyme inducing agents have increased the incidence of thyroid follicular neoplasia in rat carcinogenicity studies, thyroid function should be assessed and a secondary mechanism of hormone imbalance should be considered in the interpretation of the significance of these findings in rodents.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
McClain RMdoi
10.1177/019262338901700206subject
Has Abstractpub_date
1989-01-01 00:00:00pages
294-306issue
2eissn
0192-6233issn
1533-1601journal_volume
17pub_type
杂志文章,评审abstract::The cochlea is one of the more common targets for toxic effects, yet current toxicologic screening in animals does not routinely evaluate the cochlea as a potential target organ. Although histopathologic sections are routinely taken from the eye and the optic nerve and tract and most studies include at least 1 section...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262330002800117
更新日期:2000-01-01 00:00:00
abstract::Nephrotoxic renal injury, and especially drug nephrotoxicity is now a common cause of acute renal failure. The most common patterns of renal injury produced by nephrotoxins, tubular damage, and interstitial nephritis, are discussed here. Toxic agents which are primarily tubular toxins include certain antibiotics, cisp...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338601400106
更新日期:1986-01-01 00:00:00
abstract::Specific regions in the rodent larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. There are interspecies differences among laboratory rodents in the microscopic anat...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100604
更新日期:1993-11-01 00:00:00
abstract::Although arsenic exposure causes liver disease and/or hepatoma, little is known about molecular mechanisms of arsenic-induced liver toxicity or carcinogenesis. We investigated the effects of arsenic on expression of cancer-related genes in a rat liver following subchronic exposure to sodium arsenate (1, 10, 100 ppm in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230490261348
更新日期:2004-01-01 00:00:00
abstract::A spontaneous multicystic peritoneal mesothelioma was detected in a 108-wk-old male Fischer-344/DuCrj rat. Grossly, a tumor containing numerous, semi-transparent, variously sized, thin-walled cysts was found on the splenic serosal surface. Microscopically, each cyst was surrounded by variable amounts of loose connecti...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100111
更新日期:1993-01-01 00:00:00
abstract::Histopathologic examination of the testis from juvenile rats is often necessary to characterize the safety of new drugs for pediatric use and is a required end point in male pubertal development and thyroid function assays. To aid in evaluation and interpretation of the immature testis, the characteristic histologic f...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314547279
更新日期:2015-04-01 00:00:00
abstract::In a 13-week feeding toxicity study of grape skin extract (GSE) performed previously, 5.0% GSE showed diffuse hypertrophy and basophilia in rat parotid glands. To clarify whether the change in the parotid glands was an adverse effect of GSE, 6-week-old male F344 rats were fed a diet containing 5.0% GSE or were adminis...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623313512429
更新日期:2014-08-01 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::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::A delay in the exposure of initiated rats to orotic acid (OA) beyond a specific time frame results in a progressive loss of promotional effect in liver carcinogenesis. The current study was designed to ascertain whether the loss of promotional effect could be counteracted by pre-exposing the initiated animals to other...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500212
更新日期:1987-01-01 00:00:00
abstract::Hepatocyte suspensions prepared from inbred male Wistar-Kyoto rats were transplanted to the livers of syngeneic recipients by injection into the portal venous system immediately after partial hepatectomy. Donor cells were labelled with 51Cr in vitro before transplantation. Animals were sacrificed 1 hr, 10 hr, 48 hr, o...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338701500110
更新日期:1987-01-01 00:00:00
abstract::Existing liver perfusion models are largely limited by high degrees of ischemic and reperfusion injury and the lack of standardization. To establish a highly standardized perfusion model and minimize reperfusion injury, a porcine liver perfusion model was developed using an artificial heart pump (Buecherl Artificial H...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230590958164
更新日期:2005-01-01 00:00:00
abstract::Blood platelets play a fundamental role in hemostasis and thrombosis. The physiological role of platelets is to preserve the integrity of the cardiovascular system such that upon injury platelets are activated and serve to interrupt a potentially deleterious situation (i.e., hemorrhage). However, platelets are also in...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100210
更新日期:1993-01-01 00:00:00
abstract::The handling-induced dark neuron is a histological artifact observed in brain samples handled before fixation with aldehydes. To explore associations between dark neurons and immunohistochemical alterations in mouse brains, we examined protein products encoded by Cav3 (neuronal perikarya/neurites), Rbbp4 (neuronal nuc...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623319896263
更新日期:2020-04-01 00:00:00
abstract::Macrophages appearing in lesions are polarized toward M1 (for inflammation) and M2 (for anti-inflammation/fibrosis) types. We analyzed immunophenotypes of macrophages appearing in myocardial lesion in rats injected once with isoproterenol (10 mg/kg body weight). Inflammation following myocardial necrosis on day 1 was ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320982526
更新日期:2021-01-05 00:00:00
abstract::The usefulness of isolated adult cardiac myocytes, both in suspension and in culture, as a model system for measuring cardiotoxicity is evaluated. It has been suggested that isolated adult myocytes should preferably be cultured for such experimentation, as this restores the cells to a physiological preference for fatt...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::Glucokinase activators (GKAs) are being developed for the treatment of type 2 diabetes. The toxicity of 4 GKAs (PF-04279405, PF-04651887, piragliatin, and PF-04937319) was assessed in mice, rats, dogs, and/or monkeys. GKAs were administered for 2 to 8 weeks. Standard endpoints, glucose, and insulin were assessed. All ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314526006
更新日期:2014-06-01 00:00:00
abstract::We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine t...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/0192623314532036
更新日期:2015-02-01 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 Syrian hamster embryo (SHE) cell-transformation assay represents a short-term in vitro assay capable of predicting rodent carcinogenicity of chemicals with a high degree of concordance (LeBoeuf et al [1996]. Mutat Res 356: 85-127). The SHE assay models the earliest identifiable stage in carcinogenicity, morphologi...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262301753178546
更新日期:2001-01-01 00:00:00
abstract::The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623314559103
更新日期:2015-06-01 00:00:00
abstract::Recently, considerable attention has been focused on certain environmental contaminants--"endocrine disruptors"--of industrial origin that may mimic the action of sex hormones. Natural compounds and their effects on other types of hormonal activity (eg, on adrenal or thyroid function) have for some reason not provoked...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1177/019262330002800311
更新日期:2000-05-01 00:00:00
abstract::Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microsc...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/01926230600932455
更新日期:2006-01-01 00:00:00
abstract::The toxicities of 2'-fluorouridine (2'-FU) and 2'-fluorocytidine-HCl (2'-FC) were separately evaluated in 2 species, male Fischer 344 (F334) rats and woodchucks. Particular attention was focused on the ability of these nucleosides to induce toxicities similar to those induced by the antiviral drug fialuridine (FIAU). ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339902700601
更新日期:1999-11-01 00:00:00
abstract::Toxic injury occurs in the liver more often than any other organ. This can be attributed to the fact that virtually all ingested substances that are absorbed are first presented to the liver and that the liver is responsible for the metabolism and elimination of many substances. Drug-induced liver injury has become a ...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230590522428
更新日期:2005-01-01 00:00:00
abstract::Two-year toxicity studies were conducted on the widely used herbal products, goldenseal and milk thistle, in male and female F344/N rats and B6C3F1 mice. With goldenseal root powder, the primary finding was an increase in liver tumors in rats and mice, and with milk thistle extract, a decrease in spontaneous backgroun...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623310394211
更新日期:2011-02-01 00:00:00
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 char...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1080/019262302753559506
更新日期:2002-03-01 00:00:00
abstract::Transgenic mouse strains offer the prospect of significant benefits in the in vivo assessment of carcinogenic potential. The European Regulatory Authorities have been supportive of their inclusion as one of the second-test options in the International Conference on Harmonization of Technical Requirements for the Regis...
journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
doi:10.1080/01926230252824879
更新日期:2002-01-01 00:00:00
abstract::A comparative study of histochemical detection of eosinophils in fixed murine tissue is lacking. Five histochemical methods previously reported for eosinophil detection were quantitatively and qualitatively compared in an established murine RSV vaccine-enhanced inflammation model. Nonspecific neutrophil staining was e...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623308329342
更新日期:2009-02-01 00:00:00
abstract::Sensitive kidney safety assessment is important for successful drug development in both preclinical and clinical stages. The Food and Drug Administration recently qualified a composite measure of 6 urine creatinine-normalized biomarkers, such as clusterin, cystatin C, kidney injury molecule 1 (KIM-1), N-acetyl-β-d-glu...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623320964391
更新日期:2020-12-01 00:00:00