Abstract:
:Cyclosporine (CsA) is a universally used immunosuppressive drug which induces adverse side effects in several organs, but its impact on the heart is still controversial. Small heat shock proteins (sHSPs), such as HSP25 and alpha B-crystallin, are cytoprotective stress proteins exceptionally represented in the heart. They act as myofibrillar chaperones that help actin and desmin to maintain their optimum configuration and stability, thereby antagonizing oxidative damage. The present study examined: (1) the cardiac distribution and abundance of HSP25 and alpha B-crystallin in rats receiving CsA at a therapeutic dosage (15 mg/kg/day) for 42 days and 63 days; (2) the presence of myofibrillar proteins, such as actin, alpha-actinin and desmin following the CsA treatments; (3) the subcellular effects of prolonged CsA exposure on the cardiomyocytes by histopathology and transmission electron microscopy. After 63 days CsA intake, sHSPs translocated from a regular sarcomeric pattern to peripheral sarcolemma and intercalated discs, together with actin and desmin. In contrast, the sarcomeric alpha-actinin pattern did not change in all experimental groups. The abundance of actin and HSP25 was unchanged in every time point of treatment while after 63 days CsA, alpha B-crystallin and desmin levels significantly decreased. Furthermore CsA induced fibrosis, irregular sarcomeric alignment and damaged desmosomes. These findings indicate that following prolonged CsA exposure, the cardiac muscle network was affected. In particular, the translocation of sHSPs to intercalated discs merits special consideration as a direct compensatory mechanism to limit CsA cardiotoxicity.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Stacchiotti A,Bonomini F,Lavazza A,Rodella LF,Rezzani Rdoi
10.1016/j.tox.2009.06.007subject
Has Abstractpub_date
2009-08-21 00:00:00pages
192-8issue
3eissn
0300-483Xissn
1879-3185pii
S0300-483X(09)00306-0journal_volume
262pub_type
杂志文章相关文献
TOXICOLOGY文献大全abstract::Colicins are unusual bacterial toxins because they are directed against close relatives of the producing strain. They kill their targets in one of three distinct ways; via a ribonuclease or deoxyribonuclease activity or by forming pores in the target cell's membrane. This review deals with the steps involved in pore-f...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(94)90156-2
更新日期:1994-02-28 00:00:00
abstract::Epidemiological studies in humans and experimental work in rodents suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental toxicant, is associated with incidence of heart disease. Although TCDD toxicity depends by and large on the aryl hydrocarbon receptor (AHR), the role of the...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2016.05.006
更新日期:2016-04-29 00:00:00
abstract::To check the possible toxicity risks of the meat from swine fed with a residue producing feed additive: Carbadox, a new methodology was used. It is the "Relay Toxicity". Swine were fed with a high dose of the additive and sacrificed without any withdrawal. In such conditions meat contains a high level of residues. The...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(78)91039-9
更新日期:1978-10-01 00:00:00
abstract::Haptens are classified as low molecular chemicals with an intrinsic potential to covalently modify proteins, and many of them are strong inducers of contact hypersensitivity (CHS). CHS is T cell mediated, and hapten-specific T cells have been shown to interact with hapten-modified, MHC-associated peptides. However, th...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2004.12.015
更新日期:2005-04-15 00:00:00
abstract::Exposure of cultured rat mesangial cells to CdCl2 caused a dose- and time-dependent increase in intracellular glutathione that was significant at 0.5 microM and maximal at 1 microM Cd2+. The effect depended on glutathione synthesis and was masked by inhibiting synthesis with buthionine sulfoximine. The cells responded...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(93)90145-i
更新日期:1993-01-29 00:00:00
abstract::Butachlor is a systemic herbicide widely applied on rice, tea, wheat, beans and other crops; however, it concurrently exerts toxic effects on beneficial organisms like earthworms, aquatic invertebrates and other non-target animals including humans. Owing to the associated risk to humans, this chloroacetanilide class o...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2012.07.014
更新日期:2012-12-08 00:00:00
abstract:BACKGROUND/AIMS:Liver fibrosis has been reported to be inhibited in vivo by oleanolic and ursolic acids. However, the mechanisms of the action of those triterpenoids are poorly understood. In this study, we aimed to determine the antifibrotic potential of other triterpenes, betulin and betulinic acid, and to characteri...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2010.12.006
更新日期:2011-02-27 00:00:00
abstract::Molybdenum trioxide (MoO3) nanoparticles (NPs) embedded in polymer films have been proposed as a cheap way of producing antibacterial coatings on external surfaces. Recently, we synthesized MoO3 nanowires in a unique shape and degree of anisotropy, which enables their fast water dissolution and quick antimicrobial rea...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2020.152564
更新日期:2020-11-01 00:00:00
abstract::Male Wistar rats injected i.p. with 30 mg Fe2+/kg body weight show hepatic damage as measured by an increase in lipid peroxides which correlated with elevated serum enzymes, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH). Oral administration of spice principles, curc...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(95)03199-p
更新日期:1996-01-22 00:00:00
abstract::This article traces the evolution of risk assessment as an essential analytical tool in the federal government. In many programs and agencies, decisions cannot be made without the benefit of information from risk assessment. Although this analytical tool influences important public health and economic decisions, there...
journal_title:Toxicology
pub_type: 历史文章,杂志文章,评审
doi:10.1016/0300-483x(95)03035-e
更新日期:1995-09-01 00:00:00
abstract::The ligand-activated nuclear receptor AhR (aryl hydrocarbon receptor) mediates the response of hepatocytes to various exogenous compounds. AhR is classically activated by planar, aromatic hydrocarbons, but also by other, structurally rather unrelated compounds. Recent data show that the canonical Wnt/β-catenin signali...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2014.08.010
更新日期:2014-11-05 00:00:00
abstract::Endocrine disruptors (EDs) are exogenous substances or xenoestrogens natural or synthetic, capable of interacting with different systems and altering their normal hormonal regulation, being the reproductive system one of the most affected. EDs produce their effects not only by acting on nuclear steroid receptors, but ...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/j.tox.2013.05.014
更新日期:2013-09-06 00:00:00
abstract::The spectrum of the anti-apoptotic potential of heparin is currently under scrutiny in various tissues and under various pathological situations. In this study, the role of a low-molecular-weight heparin derivative (LMWH), certoparin in adriamycin-induced oxidative DNA damage has been evaluated in the cardiac and rena...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2005.09.009
更新日期:2006-01-16 00:00:00
abstract::The effects of di-(2-ethylhexyl)adipate (DEHA) have been compared in female F344 rats and female B6C3F1 mice fed diets containing 0-4.0% DEHA and 0-2.5% DEHA, respectively, for periods of 1, 4 and 13 weeks. In both the rat and mouse treatment with DEHA at all time points produced a dose-dependent increase in relative ...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)00125-x
更新日期:1997-12-05 00:00:00
abstract::We have previously shown that young guinea pigs repeatedly exposed to sidestream cigarette smoke (SS) develop decreased airway reactivity of the C-fiber system without changing reactivity to one of its neurotransmitters, substance P (SP). This study was designed to determine whether the decreased reactivity was due to...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(96)03403-8
更新日期:1996-09-02 00:00:00
abstract::The mechanism of delta-aminolevulinate dehydratase (delta-ALA-D) inhibition by phenyl selenoacetylene in vitro was investigated in this study. Phenyl selenoacetylene (40-400 microM) inhibition of delta-aminolevulinate dehydratase from rat liver (low speed supernatant fraction, S1 fraction) was partially prevented by i...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.08.001
更新日期:2005-01-31 00:00:00
abstract::The rodent Hershberger assay has been used predominantly by the pharmaceutical industry to evaluate androgenic and antiandrogenic chemicals for potential therapeutic use. However, this assay has not yet been formally validated and standardized for use in toxicology testing. There are many variations in the protocol us...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00361-4
更新日期:2001-05-11 00:00:00
abstract::Cultures of the human cell line NHIK 3025 were exposed over an 18-month period to 0.5 mumol/1 potassium dichromate (K2Cr2O7) containing 1 mumol/1 hexavalent chromium. The chronically exposed cells increased their tolerance to K2Cr2O7 in comparison to control populations. The doubling time of the chronically exposed ce...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(81)90083-4
更新日期:1981-01-01 00:00:00
abstract::The usefulness of cDNA-directed expression of human hepatic P450s in yeast for the in vitro study of drug metabolism is emphasized. The major advantages of yeast expression are: (i) relatively high yields of heterologous P450 (approximately 5-10 nmol/l of culture medium) can be obtained; (ii) the expressed P450s are d...
journal_title:Toxicology
pub_type: 杂志文章,评审
doi:10.1016/0300-483x(93)90058-z
更新日期:1993-10-05 00:00:00
abstract::Dioxins, including the most toxic congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), exert diverse biological effects in humans and animals. Host resistance, especially to virus infections, is considered one of the most sensitive targets of TCDD-toxicity, while a recent study showed that the vulnerability to TCDD o...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(01)00535-2
更新日期:2002-01-15 00:00:00
abstract::To investigate the toxic effect of terephthalic acid (TPA) on testicular functions of rats, male Sprague-Dawley rats were orally administered TPA in diet at the levels 0 (control), 0.2, 1 and 5% for 90 days. Testicular functions were assessed by histopathology, testicular sperm head counts, daily sperm production, spe...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2004.03.024
更新日期:2004-09-01 00:00:00
abstract::We have examined the effect of pretreatment with a potent protein kinase C (PKC) inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine (H-7), against metabolic alterations induced by sodium cyanide (NaCN), 4.2 mg/kg, in brain of anesthetized male micropigs (6-10 kg). Brain high energy phosphates were analyzed usin...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(95)03078-t
更新日期:1995-06-26 00:00:00
abstract::Since predictive differentiation of photoallergenic from phototoxic reactions, induced by low molecular weight compounds, represents a current problem, we tried to improve the differentiation between the two reactions by using a modified protocol of the local lymph node assay (LLNA). Briefly, groups of female BALB/c m...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/s0300-483x(97)00156-x
更新日期:1998-02-06 00:00:00
abstract::Evidence from epidemiological studies indicates that acute exposure to airborne pollutants is associated with an increased risk of morbidity and mortality attributed to cardiovascular diseases. The present study investigated the effects of combustion-derived ultrafine particles (diesel exhaust particles) as well as en...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2008.08.018
更新日期:2008-11-20 00:00:00
abstract::It is reported that gambogic acid (GA), the main active compound of gamboge which is a dry resin extracted from Garcinia hanburyi tree, has potent antitumor activity both in vivo and in vitro. Activation of mitochondrial apoptotic pathway in cancer cells is one effective therapy for cancer treatment. In the present st...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.03.010
更新日期:2009-06-16 00:00:00
abstract::The ubiquitous presence of nanoparticles (NPs) together with increasing evidence linking them to negative health effects points towards the need to develop the understanding of mechanisms by which they exert toxic effects. This study was designed to investigate the role of surface area and oxidative stress in the cell...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2009.04.001
更新日期:2009-06-16 00:00:00
abstract::It is accepted practice in presenting organ weight data to express the results relative to the animal's body weight. The data presented suggest that in rats no benefits are obtained from this method either in reducing the variability of the data or in removing bias due to different body weights. By using simulated dat...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(76)90050-0
更新日期:1976-03-01 00:00:00
abstract::Mechanisms responsible for resistance to Cd-induced testicular necrosis in inbred mice were investigated using strains resistant (A/J) or susceptible (129/J) to Cd-induced testicular damage. Cadmium accumulation was measured in testes of both strains 15 min, 30 min, 1 h, 2 h, 6 h, 12 h and 24 h after intravenous injec...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(84)90126-4
更新日期:1984-03-01 00:00:00
abstract::The urinary metabolites from repeated oral doses of 3.7 mg o-phenyl phenol (OPP) to mature and immature dogs and cats were studied. At both age levels, dogs excreted significantly more OPP as sulfate and glucuronide than did cats. Puppies produced 4 times the level of glucuronides than mature dogs. No such age differe...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/0300-483x(80)90016-5
更新日期:1980-01-01 00:00:00
abstract::In the clinical setting, antidotes are generally administered after the occurrence of a drug overdose. Therefore, the most pertinent evaluation of any new agent should model human exposure. This study tested whether acetaminophen (APAP) hepatotoxicity was reversed when S-adenosyl-L-methionine (SAMe) was administered a...
journal_title:Toxicology
pub_type: 杂志文章
doi:10.1016/j.tox.2007.10.027
更新日期:2008-02-03 00:00:00