Abstract:
:The clinical uses of estrogens are associated with serious adverse effects, so the experimental toxicology of these compounds is under continuous review. Structurally different estrogens have qualitatively similar effects in animals when given in amounts way above the rodent uterotrophic dose. Toxicity still tends, however, to be related to estrogenic potency. Carnivores are more susceptible than rodents. Changes in reproductive, mammary and endocrine tissues are consistent with hyperestrogenism. Growth rate is decreased in rats and mice, but weight gains have been reported in other species. The weights of the liver, spleen, thymus and other organs are changed. Liver damage can occur. Susceptibility declines in the order cat, ferret, rat and mouse, dog. Clotting changes seen in the rat are secondary to liver damage. Moderate doses elicit anemia in rats, but lethal bone marrow depression in dogs and ferrets. Death is associated with hemorrhage. Antiestrogens modify aspects of estrogen toxicity in the rat, but not in the ferret. The predictive value of animal studies for humans has been disappointing. Interspecies variations at the hypothalamic-pituitary axis appear to have an important bearing on the differential activities of estrogens and antiestrogens across the species.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Hart JEdoi
10.1016/0163-7258(90)90087-isubject
Has Abstractpub_date
1990-01-01 00:00:00pages
203-18issue
2eissn
0163-7258issn
1879-016Xpii
0163-7258(90)90087-Ijournal_volume
47pub_type
杂志文章,评审abstract::Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2017.10.002
更新日期:2018-03-01 00:00:00
abstract::Increasing evidence of a critical role played by the bronchial epithelium in airway homeostasis is opening new therapeutic avenues. Its unique situation at the interface with the environment suggests that the subtle regulation orchestrated by the epithelium between tolerance and specific immune response might be impai...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2013.07.008
更新日期:2013-12-01 00:00:00
abstract::The cardiovascular system is highly organised in time; blood pressure (BP), heart rate (HR), peripheral resistance, pressure and the release/activity of vasodilating hormones all display pronounced circadian variations. Pathophysiological events within the cardiovascular system are also not random, as shown for instan...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.11.008
更新日期:2006-09-01 00:00:00
abstract::Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life, and health and causes huge economic losses. Increasing evidence has shown that peroxisome proliferator-activated receptors (PPARs) can regulate the progression of cardiac fibrosis. For the first time, ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107702
更新日期:2020-10-04 00:00:00
abstract::Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of development, plasticity and, recently, addiction. Decreased neurotrophic activity may be involved in ethanol-induced neurodegeneration in the adult brain and in the etiology of alcohol-related neurodevelopmental disorders. This can occur through de...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.01.003
更新日期:2008-04-01 00:00:00
abstract::Cardiovascular diseases cause more mortality and morbidity worldwide than any other diseases. Although many intracellular signaling pathways influence cardiac physiology and pathology, the mitogen-activated protein kinase (MAPK) family has garnered significant attention because of its vast implications in signaling an...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.05.013
更新日期:2014-11-01 00:00:00
abstract::Integrins are heterodimeric cell surface receptors, which principally mediate the interaction between cells and their extracellular microenvironments. Because of their pivotal roles in cancer proliferation, survival, invasion and metastasis, integrins have been recognized as promising targets for cancer treatment. As ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2013.05.007
更新日期:2013-10-01 00:00:00
abstract::Cardiovascular disease (CVD) continues to be a leading cause of death worldwide with atherosclerosis being the major underlying pathology. The interplay between lipids and immune cells is believed to be a driving force in the chronic inflammation of the arterial wall during atherogenesis. Atherosclerosis is initiated ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.08.012
更新日期:2019-01-01 00:00:00
abstract::The receptors involved in bitter taste perception (bitter taste receptors--T2Rs) constitute a family of G-protein-coupled receptors, of which around 29 subtypes have been identified in humans. T2R expression was initially thought to be confined to the oral cavity but has recently been described in a range of other tis...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.08.001
更新日期:2015-11-01 00:00:00
abstract::Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.01.007
更新日期:2018-06-01 00:00:00
abstract::The ever-growing global burden of congestive heart failure (CHF) and type 2 diabetes mellitus (T2DM) as well as their co-existence necessitate that anti-diabetic pharmacotherapy will modulate the cardiovascular risk inherent to T2DM while complying with the accompanying restrictions imposed by CHF. The thiazolidinedio...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.09.007
更新日期:2016-12-01 00:00:00
abstract::Numerous pro-inflammatory cytokines have been implicated in the pathogenesis of several cardiovascular diseases. Interleukin (IL)-33 is a new member of the IL-1 family of cytokines that promotes Th2 type immune responses by signaling through the ST2L and IL-1RAcP dimeric receptor complex. Furthermore, the biological e...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2011.02.005
更新日期:2011-08-01 00:00:00
abstract::Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed the therapeutic management of solid tumors, particularly ovarian cancer. Initially studied in BRCA deficient tumors, the Food and Drug Administration (FDA) indications have expanded to include other homologous recombination deficient tumors as well as bio...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107588
更新日期:2020-09-01 00:00:00
abstract::Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is m...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2010.04.004
更新日期:2010-09-01 00:00:00
abstract::Progress in methods of investigating endothelial function in humans has led to the demonstration that endothelial dysfunction is an early process involved in the pathophysiology of cardiovascular diseases, and represents a new independent therapeutic target that may help to improve patient health. The administration o...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2011.03.015
更新日期:2011-07-01 00:00:00
abstract::As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were w...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2020.107658
更新日期:2020-12-01 00:00:00
abstract::It is now generally accepted that protein phosphorylation-dephosphorylation has a role in the regulation of essentially all cellular functions. Thus, it is of interest that this process is involved in signal transduction. Nonetheless, the extent to which protein phosphorylation participates in signaling is truly remar...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(98)00056-4
更新日期:1999-05-01 00:00:00
abstract::Pokeweed antiviral protein (PAP) is a ribosome-inactivating protein (RIP) that inactivates ribosomes by the removal of a single adenine from ribosomal RNA. The studies summarized in our review concern the nature and application of this novel therapeutic agent. We describe how researchers continue to elucidate the stru...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(92)90053-3
更新日期:1992-01-01 00:00:00
abstract::Decades of research have established that the biological functions of thyrotropin-releasing hormone (TRH) extend far beyond its role as a regulator of the hypothalamic-pituitary-thyroid axis. Gary et al. [Gary, K.A., Sevarino, K.A., Yarbrough, G.G., Prange, A.J. Jr., Winokur, A. (2003). The thyrotropin-releasing hormo...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.09.004
更新日期:2009-01-01 00:00:00
abstract::Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate (S1P), play many important roles in cellular activities. Ceramide and sphingosine inhibit cell proliferation and induce cell apoptosis while S1P has the opposite effect. Maintaining a metabolic balance of sphingolipids is essential for...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.10.011
更新日期:2019-03-01 00:00:00
abstract::Necrosis of skeletal muscle is produced by two types of snake venom components: single chain peptides consisting of 42-44 amino acid residues and phospholipases A2 representing either single chain proteins or existing as complexes of several enzyme subunits or combined with other nonenzymatic proteins. Vacuolation, ly...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(90)90081-c
更新日期:1990-01-01 00:00:00
abstract::Since the first description of their opioid properties three decades ago, dynorphins have increasingly been thought to play a regulatory role in numerous functional pathways of the brain. Dynorphins are members of the opioid peptide family and preferentially bind to kappa opioid receptors. In line with their localizat...
journal_title:Pharmacology & therapeutics
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.pharmthera.2009.05.006
更新日期:2009-09-01 00:00:00
abstract::Organic anion transporters (OATs), which belong to the superfamily SLC22A, are key determinants in the absorption, distribution, and excretion of a diverse array of environmental toxins, and clinically important drugs, and, therefore, are critical for the survival of mammalian species. Alteration in the function of th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2009.08.002
更新日期:2010-01-01 00:00:00
abstract::Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed....
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2015.01.001
更新日期:2015-05-01 00:00:00
abstract::beta(2)-adrenoceptor agonists are the mainstay for the acute symptomatic treatment of asthma and provide effective bronchoprotection to a wide range of bronchoconstrictor agents. However, over the past 4 decades there has been a continuing debate concerning whether regular chronic treatment with these drugs may be doi...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.04.009
更新日期:2007-09-01 00:00:00
abstract::S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or animals normally results in an accumulation ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(97)00089-2
更新日期:1998-02-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with a high mortality rate. Genetic and biochemical studies have shown that RAS signaling mediated by KRAS plays a pivotal role in disease initiation, progression and drug resistance. RAS signaling affects several cellular processes in PDAC, includ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.09.003
更新日期:2016-12-01 00:00:00
abstract::A variety of drug transporters expressed in the body control the fate of drugs by affecting absorption, distribution, and elimination processes. In the small intestine, transporters mediate the influx and efflux of endogenous or exogenous substances. In clinical pharmacotherapy, ATP-dependent efflux transporters (ATP-...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.06.005
更新日期:2006-01-01 00:00:00
abstract::Microsomal P450-mediated monooxygenase activity supported by NADPH requires an interaction between flavoprotein NADPH-cytochrome P450 reductase and cytochrome P450. These proteins have been identified as the simplest system (with the inclusion of a phospholipid (PL) component) that possesses monooxygenase function; ho...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0163-7258(03)00031-7
更新日期:2003-05-01 00:00:00
abstract::Primaquine is the only antimalarial drug available to clinicians for the treatment of relapsing forms of malaria. Primaquine development and usage dates back to the 1940s and has been administered to millions of individuals to treat and eliminate malaria infections. Primaquine therapy is not without disadvantages, how...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2016.03.011
更新日期:2016-05-01 00:00:00