Abstract：
:Cyclosporin (Cs), a cyclic nonpolar undecapeptide of fungal origin, has potent immunosuppressive and antiparasitic activities, and renal and hepatic toxicities, the mechanisms of which are not worked out. Many nephrotoxins and hepatotoxins are predictably more or less harmful, depending upon the circadian stage at which they are administered. In order to find treatment schedules that might damage the animal least, the toxicity of 20 mg kg-1 day-1 of Cs given intraperitoneally was studied at six different circadian stages in adult male Lewis rats. Cs toxicity was gauged by body temperature decline, body weight loss, and survival time. Rectal temperatures over a 24-hr span during the 2 days prior to the first death revealed that rats treated during darkness were 1.6 +/- 0.3 degree C cooler than vehicle-treated controls, whereas rats treated during the light span were only 0.4 +/- 0.2 degree C cooler than controls (p less than 0.01). Rats treated in darkness lost twice as much weight compared to those treated in light (20 +/- 2 versus 10 +/- 2%, p less than 0.01). Rats receiving daily Cs in the dark span lived an average of 28 +/- 5 days compared with 44 +/- 4 days for animals getting Cs during the light span (p less than 0.05). Three separate nonspecific measures of drug toxicity confirmed that there was substantial circadian stage dependence to Cs toxicity. The safest time for the drug in rats was 2 to 10 hr after lighting onset, a time when rats are usually beginning their diurnal rest and/or sleep span.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Magnus G,Cavallini M,Halberg F,Cornelissen G,Sutherland DE,Najarian JA,Hrushesky WJdoi
10.1016/0041-008x(85)90279-0subject
Has Abstractpub_date
1985-01-01 00:00:00pages
181-5issue
1eissn
0041-008Xissn
1096-0333pii
0041-008X(85)90279-0journal_volume
77pub_type
杂志文章abstract：:Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been implicated in various skin diseases. We formulated the hypothesis that a high-fat diet may influence the UV-induced inflammatory responses in the skin. C57BL/6 mice were fed a high-fat diet or control diet and exposed to UVB radiation (120...
journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/0041-008x(83)90351-4
更新日期：1983-03-30 00:00:00
abstract：INTRODUCTION:Noncirrhotic portal fibrosis has been reported to occur in humans due to prolonged intake of arsenic contaminated water. Further, oxystress and hepatic fibrosis have been demonstrated by us in chronic arsenic induced hepatic damage in murine model. Cytokines like tumor necrosis factor alpha (TNF-alpha) and...
journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
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更新日期：1985-01-01 00:00:00
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/j.taap.2019.01.016
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/j.taap.2012.04.030
更新日期：2012-07-15 00:00:00
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/0041-008x(92)90296-5
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(91)90330-h
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journal_title：Toxicology and applied pharmacology
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doi：10.1016/j.taap.2003.10.009
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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journal_title：Toxicology and applied pharmacology
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更新日期：1987-04-01 00:00:00
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journal_title：Toxicology and applied pharmacology
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abstract：BACKGROUND AND PURPOSE:Tiotropium bromide (TB) is a long acting muscarinic receptor antagonist used to manage chronic obstructive pulmonary disease (COPD). Recent meta-analyses suggest an increased risk of cardiovascular events with TB. Ca2+/calmodulin dependent kinase II (CaMKII) and L-type Ca2+ channels regulate Ca2+...
journal_title：Toxicology and applied pharmacology
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更新日期：2019-12-01 00:00:00
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journal_title：Toxicology and applied pharmacology
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更新日期：2014-10-15 00:00:00
abstract：:Molecule-targeted therapies like those against the epidermal growth factor receptor (EGFR) are becoming widely used in the oncology clinic. With improvements in treatment efficacy, many cancers are being treated as chronic diseases, with patients having prolonged exposure to several therapies that were previously only...
journal_title：Toxicology and applied pharmacology
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更新日期：2008-05-01 00:00:00
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journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1006/taap.1994.1101
更新日期：1994-05-01 00:00:00
abstract：:gamma-Hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to be a seizure-inducing agent in mammals. gamma-HCH and two non-convulsant isomers of HCH (alpha and delta) were compared as to their CNS-related pharmacological and biochemical effects. gamma-HCH was a potent se...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(88)90034-8
更新日期：1988-03-30 00:00:00
abstract：:Tolerance to several toxic effects of Cd, including lethality, has been shown following pretreatment with Cd. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity. Rats were challenged with Cd (2.0, 3.0, 4.0, or 5.0 mg/kg, iv) 24 hr after pretreatment with saline (2 ml/kg, sc) o...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/0041-008x(84)90283-7
更新日期：1984-07-01 00:00:00
abstract：:The skin cancer enhancing effect of chromium (in male mice) and nickel in UVR-irradiated female Skh1 mice was investigated. The dietary vitamin E and selenomethionine were tested for prevention of chromium-enhanced skin carcinogenesis. The mice were exposed to UVR (1.0 kJ/m(2) 3 x weekly) for 26 weeks either alone, or...
journal_title：Toxicology and applied pharmacology
pub_type： 杂志文章
doi：10.1016/j.taap.2007.03.030
更新日期：2007-06-15 00:00:00
