Protection in the late stages of paracetamol-induced liver cell injury with fructose, cyslosporin A and trifluoperazine.


:A fixed combination of the three components, fructose, cyclosporin A and trifluoperazine (FCAT), was found to protect in the late stage of paracetamol-induced liver cell injury both in vivo and in an in vivo/in vitro system. Rats pre-induced with phenobarbitone were given a paracetamol dose of 1 g/kg i.p. The combination of FCAT was given orally 3 h or 3 and 8 h after paracetamol and was able to afford protection as seen by measurements of plasma alanine transaminase (ALT) levels at 24 h. In the in vivo/in vitro system, rats pre-induced with phenobarbitone were dosed with paracetamol 1 g/kg i.p. to initiate injury and liver slices were then taken 3, 4 and 5 h later. The liver slices were then incubated for up to 18 h with the protective agents (FCAT) and the progression of injury followed. Injury was assessed by lactate dehydrogenase (LDH) leakage into the medium and potassium content of the slices. FCAT significantly reduced the injury even as assessed after 5 h in vivo initiation and 18 h progression in vitro. Mitochondrial membrane potential was also maintained in the FCAT-treated liver slices from paracetamol-treated rats as seen by the ability to maintain a gradient of triphenyl methyl phosphonium (TPMP+) between the cell and external medium. All three compounds are required for protection, indicating that more than one event is critical to the survival of the cell and each target point needs to be protected for effective long-term cell survival. The in vivo/in vitro system has been found to give a better comparability to the in vivo situation than injury models that take 6 h or less.






Beales D,McLean AE




Has Abstract


1996-03-18 00:00:00














  • An assessment of antigenic potential of beta-lactam antibiotics, low molecular weight drugs, using guinea pig models.

    abstract::Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test method...


    pub_type: 杂志文章


    authors: Hattori H,Yamaguchi F,Wagai N,Kato M,Nomura M

    更新日期:1997-11-21 00:00:00

  • Cephaloridine nephrotoxicity in aging male Fischer-344 rats.

    abstract::Age-related differences in susceptibility to cephaloridine nephrotoxicity were evaluated in male Fischer-344 rats. Rats, 2.5, 4, 10-12 and 27-29 months old, were administered a single intraperitoneal dose of cephaloridine and renal function evaluated 24 h later. Susceptibility to cephaloridine-induced nephrotoxicity w...


    pub_type: 杂志文章


    authors: Goldstein RS,Pasino DA,Hook JB

    更新日期:1986-01-01 00:00:00

  • Allergenicity evaluation of p-chloro-m-cresol and p-chloro-m-xylenol by non-radioactive murine local lymph-node assay and multiple-dose guinea pig maximization test.

    abstract::p-Chloro-m-cresol (PCMC) and p-chloro-m-xylenol (PCMX) are known to cause allergic contact dermatitis. For risk assessment of skin sensitizers, information on dose-response profiles in the induction and elicitation phases and cross-reactivity with analogous chemicals are important. In the non-radioactive local lymph-n...


    pub_type: 杂志文章


    authors: Yamano T,Shimizu M,Noda T

    更新日期:2003-08-28 00:00:00

  • Hepatic and renal Bcrp transporter expression in mice treated with perfluorooctanoic acid.

    abstract::The breast cancer resistance protein (Bcrp) is an efflux transporter that participates in the biliary and renal excretion of drugs and environmental chemicals. Recent evidence suggests that pharmacological activation of the peroxisome proliferator activated receptor alpha (PPARα) can up-regulate the hepatic expression...


    pub_type: 杂志文章


    authors: Eldasher LM,Wen X,Little MS,Bircsak KM,Yacovino LL,Aleksunes LM

    更新日期:2013-04-05 00:00:00

  • Toxicity of the novel animal-derived anticancer agent, VRCTC-310: acute and subchronic studies in beagle dogs.

    abstract::Acute and subchronic toxicities of VRCTC-310, a combination product of crotoxin (CT) and cardiotoxin (CD), which has shown antitumor activity in vivo, have been studied in Beagle dogs. Single i.m. doses of 0.25, 0.5 and 1.0 mg/kg resulted in dose-dependent local muscular toxicity consisting of myofiber atrophy, inters...


    pub_type: 杂志文章


    authors: DeTolla LJ,Stump KC,Russell R,Viskatis LJ,Vidal JG,Newman RA,Etcheverry MA

    更新日期:1995-05-05 00:00:00

  • Long-term toxicity and reproduction studies with metaldehyde in rats.

    abstract::Rats received 0, 200, 1000 and 5000 ppm metaldehyde in the diet for 2 years. Reproduction studies over three generations using the same dietary levels were carried out. In the third litter of each generation attention was paid to possible embryotoxic or teratogenic effects. The parameters studied included growth, food...


    pub_type: 杂志文章


    authors: Verschuuren HG,Kroes R,Den Tonkelaar EM,Berkvens JM,Helleman PW,Van Esch GJ

    更新日期:1975-01-01 00:00:00

  • Mutagenic potential of cis-dichlorodiammine platinum II in rodents.

    abstract::The ability of cis-dichlorodiammine platinum II to cause chromosomal aberrations in rats and dominant lethality in mice was studied. Five daily intraperitoneal doses ranging from 0.25 to 2.00 mg/kg/day failed to result in the observance of dominant lethal mutations in mice. Intraperitoneal doses of 0.13 and 0.52 mg/kg...


    pub_type: 杂志文章


    authors: Levine BS,Preache MM,Pergament E

    更新日期:1980-01-01 00:00:00

  • Fusarenon-X induced apoptosis in HL-60 cells depends on caspase activation and cytochrome c release.

    abstract::Fusarenon-X (FX), a trichothecene mycotoxin, is well known to be cytotoxic to mammalian cells. Our previous study revealed that FX induced apoptosis in mouse thymocytes both in vivo and in vitro. We investigated the mode of apoptosis induced by FX using HL-60 cell culture. When FX at a final concentration of 0.5 micro...


    pub_type: 杂志文章


    authors: Miura K,Aminova L,Murayama Y

    更新日期:2002-03-20 00:00:00

  • Long-term arsenite exposure induces testicular toxicity by redox imbalance, G2/M cell arrest and apoptosis in mice.

    abstract::Inorganic arsenic (iAs), a ubiquitous element and a natural drinking water contaminant, has been found to impair male reproductive function. However, the effect of long-term exposure to arsenic on testis damage and its underlying mechanisms still require further evaluation. In the study, male C57BL/6 mice (4 weeks) we...


    pub_type: 杂志文章


    authors: Zeng Q,Yi H,Huang L,An Q,Wang H

    更新日期:2019-01-01 00:00:00

  • The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis.

    abstract::Although several specific micronutrient deficiencies are associated with disease progression and increased mortality risk in HIV/AIDS, and even a simple multivitamin/mineral supplement can prolong survival, this is typically viewed merely as nutritional support of the immune system, and only necessary if there are def...


    pub_type: 杂志文章


    authors: Taylor EW

    更新日期:2010-11-28 00:00:00

  • Exploration of small RNA biomarkers for testicular injury in the serum exosomes of rats.

    abstract::Testicular injury is often observed in drug development. Serum hormones are usually used as noninvasive biomarkers for testicular injury; however, their sensitivities are low. Therefore, it is difficult to monitor testicular injury in drug development. In recent years, molecules in body fluid exosomes have attracted a...


    pub_type: 杂志文章


    authors: Kawata R,Kagawa T,Koya Y,Kajiyama H,Oda S,Yokoi T

    更新日期:2020-07-01 00:00:00

  • Molecular pathological analysis on the mechanism of liver carcinogenesis in dicyclanil-treated mice.

    abstract::To investigate the mechanism of hepatocarcinogenesis due to dicyclanil (DC), an insect growth regulator for sheep, histopathological and molecular biological analyses were performed in the liver of male ICR mice fed on a diet containing 1500 ppm of DC for 2 weeks (Experiment I; Exp. I). In gene expression analyses usi...


    pub_type: 杂志文章


    authors: Moto M,Okamura M,Muto T,Kashida Y,Machida N,Mistumori K

    更新日期:2005-02-28 00:00:00

  • Inorganic tin -- a new selective inducer of the murine coumarin 7-hydroxylase (CYP2A5).

    abstract::The coumarin 7-hydroxylase of mice (Coh, CYP2A5) is known to be highly selectively inducible by both a set of heavy metals such as cobalt, indium and cerium and a variety of organic nitrogen-containing heteroaromatic compounds such as 3-amino-1,2,4-triazole, pyrazine and pyrazole. The investigations presented reveal t...


    pub_type: 杂志文章


    authors: Emde B,Tegtmeier M,Hahnemann B,Legrum W

    更新日期:1996-04-15 00:00:00

  • Effect of viability of actinomycete spores on their ability to stimulate production of nitric oxide and reactive oxygen species in RAW264.7 macrophages.

    abstract::Spores of actinomycetes, mesophilic gram-positive bacteria, isolated from moldy houses, induced the expression of inducible NO-synthase (iNOS) with a subsequent NO-production in RAW264.7 macrophages. No differences were detected between production of nitric oxide (NO) by alive or irradiated spores of different strains...


    pub_type: 杂志文章


    authors: Hirvonen MR,Ruotsalainen M,Savolainen K,Nevalainen A

    更新日期:1997-12-26 00:00:00

  • The role of prostaglandin E2 receptor EP1 in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced neonatal hydronephrosis in mice.

    abstract::Prostaglandin E2 (PGE2) is a critical factor in the pathogenesis of dioxin-induced neonatal hydronephrosis. Since the PGE2 receptor has four subtypes, EP1 - EP4, this study was aimed to challenge the hypothesis that at least one of the four subtypes is responsible for the pathogenesis of dioxin-induced hydronephrosis....


    pub_type: 杂志文章


    authors: Aida-Yasuoka K,Nishimura N,Fujisawa N,Endo N,Narumiya S,Tohyama C

    更新日期:2019-03-01 00:00:00

  • Effects of sodium pyridinethione on the uptake and distribution of nickel, cadmium and zinc in pregnant and non-pregnant mice.

    abstract::Oral administration of sodium pyridinethione together with 63Ni2+, 109Cd2+ or 65Zn2+ to non-pregnant mice resulted in very markedly increased levels of the metals in several tissues in comparison with animals given the metals alone. For 63Ni2+ the sodium pyridinethione induced a strong labelling of the pancreatic isle...


    pub_type: 杂志文章


    authors: Jasim S,Tjälve H

    更新日期:1986-03-01 00:00:00

  • Effect of P-glycoprotein on the availability of oxime reactivators in the brain.

    abstract::The ability to overcome cellular barriers in the body is crucial for efficient delivery of drugs to the target where intervention is needed. For drugs acting in the brain it is essential to overcome the blood-brain barrier (BBB). Such drugs include antidotes for the treatment of organophosphate poisoning, a current wa...


    pub_type: 杂志文章


    authors: Kobrlova T,Soukup O

    更新日期:2020-10-01 00:00:00

  • Chromosomal composition of micronuclei in mouse bone marrow treated with rifampicin and nicotine, analyzed by multicolor fluorescence in situ hybridization with pancentromeric DNA probe.

    abstract::The mechanism underlying the induction of micronuclei induced by rifampicin and nicotine in mouse bone marrow was investigated by fluorescence in situ hybridization assay using mouse minor satellite DNA probe. Colchicine and mitomycin, known to be predominantly clastogenic and aneugenic, respectively were used as posi...


    pub_type: 杂志文章


    authors: Attia SM

    更新日期:2007-06-03 00:00:00

  • Subchronic exposure to ethyl tertiary butyl ether resulting in genetic damage in Aldh2 knockout mice.

    abstract::Ethyl tertiary butyl ether (ETBE) is biofuel additive recently used in Japan and some other countries. Limited evidence shows that ETBE has low toxicity. Acetaldehyde (AA), however, as one primary metabolite of ETBE, is clearly genotoxic and has been considered to be a potential carcinogen. The aim of this study was t...


    pub_type: 杂志文章


    authors: Weng Z,Suda M,Ohtani K,Mei N,Kawamoto T,Nakajima T,Wang RS

    更新日期:2013-09-15 00:00:00

  • Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells.

    abstract::Adrenocortical carcinoma (ACC) is an extremely rare and aggressive endocrine malignancy with a poor prognosis. The most common symptom of ACC is hypercortisolism (Cushing's syndrome), which has the highest mortality. Mitotane is used as a steroidogenesis inhibitor for Cushing's syndrome or as a chemical adrenalectomy ...


    pub_type: 杂志文章


    authors: Lin CW,Chang YH,Pu HF

    更新日期:2012-08-16 00:00:00

  • Chemical models for toxic metabolites of bromobenzene derivatives. Relative toxicity toward isolated hepatocytes.

    abstract::In the rat the hepatotoxicity of bromobenzene is greatly enhanced by the introduction of a cyano group adjacent to the bromine (i.e. o-bromobenzonitrile). Epoxide metabolites of these aryl halides are believed to be the actual toxic species, but epoxides of the latter compound also possess a second site of chemical re...


    pub_type: 杂志文章


    authors: Gottschall DW,Harder RR,Wiley RA,Hanzlik RP

    更新日期:1984-06-01 00:00:00

  • Efficacy of an oximate-based skin decontaminant against organophosphate nerve agents determined in vivo and in vitro.

    abstract::Recent Canadian research efforts have been directed towards the development of a reactive skin decontaminant (RSD) lotion active against classical nerve agents and mustard. The formulation presently under study consists of a 1.25 molal solution of potassium 2,3-butanedione monoximate (KBDO) in polyethylene glycol meth...


    pub_type: 杂志文章


    authors: Sawyer TW,Parker D,Thomas N,Weiss MT,Bide RW

    更新日期:1991-05-01 00:00:00

  • Effects of combustion-derived ultrafine particles and manufactured nanoparticles on heart cells in vitro.

    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...


    pub_type: 杂志文章


    authors: Helfenstein M,Miragoli M,Rohr S,Müller L,Wick P,Mohr M,Gehr P,Rothen-Rutishauser B

    更新日期:2008-11-20 00:00:00

  • Lactational exposure to low levels of the six indicator non-dioxin-like polychlorinated biphenyls induces DNA damage and repression of neuronal activity, in juvenile male mice.

    abstract::Previously, we evaluated the effects of lactational exposure to a representative mixture of the six indicator non-dioxin-like polychlorinated biphenyls (∑6 NDL-PCBs) at low levels on the neurobiological changes and developmental/behavioral performances in mice. In this study, we analyzed the global gene expression pro...


    pub_type: 杂志文章


    authors: Elnar AA,Desor F,Marin F,Soulimani R,Nemos C

    更新日期:2015-02-03 00:00:00

  • Technical pentabromodiphenyl ether and hexabromocyclododecane as activators of the pregnane-X-receptor (PXR).

    abstract::Technical pentabrominated diphenyl ether (pentaBDE mix) is a mixture of polybrominated diphenyl ethers (PBDEs) which has been widely used as a flame retardant. Since its ban in several countries it has been replaced by other brominated flame retardants such as hexabromocyclododecane (HBCD). Both certain PBDE congeners...


    pub_type: 杂志文章


    authors: Fery Y,Buschauer I,Salzig C,Lang P,Schrenk D

    更新日期:2009-10-01 00:00:00

  • Different reactivity of primary fibroblasts and endothelial cells towards crystalline silica: A surface radical matter.

    abstract::Quartz is a well-known occupational fibrogenic agent able to cause fibrosis and other severe pulmonary diseases such as silicosis and lung cancer. The silicotic pathology owes its severity to the structural and chemo-physical properties of the particles such as shape, size and abundance of surface radicals. In earlier...


    pub_type: 杂志文章


    authors: Pozzolini M,Vergani L,Ragazzoni M,Delpiano L,Grasselli E,Voci A,Giovine M,Scarfì S

    更新日期:2016-06-15 00:00:00

  • The 3-methylcholanthrene-mimetic effect of 4,4'-dichlorobiphenyl-treatment on phenacetin-induced hepatic glutathione depletion and liver microsomal phenacetin O-deethylation in rats.

    abstract::Both 4,4'-dichlorobiphenyl (4,4'-DCB) and 3-methylcholanthrene (3-MC) caused a substantial increase of phenacetin-induced hepatic glutathione (GSH) depletion, whereas phenobarbital (PB) had no effect, suggesting that 4,4'-DCB possesses cytochrome P-448 inducing activity. The O-deethylation of phenacetin by liver micro...


    pub_type: 杂志文章


    authors: van Bree L,Redegeld FA,de Vries J

    更新日期:1986-12-15 00:00:00

  • Environmental polycyclic aromatic hydrocarbons affect androgen receptor activation in vitro.

    abstract::Nine structurally different polycyclic aromatic hydrocarbons (PAHs) were tested for their ability to either agonize or antagonize the human androgen receptor (hAR) in a sensitive reporter gene assay based on CHO cells transiently cotransfected with a hAR vector and an MMTV-LUC vector. Benz[a]anthracene (B[a]A), benzo[...


    pub_type: 杂志文章


    authors: Vinggaard AM,Hnida C,Larsen JC

    更新日期:2000-04-14 00:00:00

  • Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression.

    abstract::In the present study, we investigated the inducibility of the drug conjugate transporter genes MRP1 and MRP2 by redox-active compounds such as tertiary butylated hydroquinone (tBHQ) and quercetin and by chemicals known to activate the pregnane X receptor (PXR) such as rifampicin and clotrimazol and by the metalloid co...


    pub_type: 杂志文章


    authors: Kauffmann HM,Pfannschmidt S,Zöller H,Benz A,Vorderstemann B,Webster JI,Schrenk D

    更新日期:2002-02-28 00:00:00

  • The effect of initiating doses of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene on the expression of PAH activating enzymes and its modulation by plant phenols.

    abstract::Polycyclic aromatic hydrocarbons (PAHs) including benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) are environmental pollutants, which undergo metabolic activation to exert their carcinogenic effects. Our earlier studies showed that naturally occurring plant phenols, protocatechuic, chlorogenic, tannic...


    pub_type: 杂志文章


    authors: Szaefer H,Krajka-Kuźniak V,Baer-Dubowska W

    更新日期:2008-09-29 00:00:00