Lactulose attenuates METH-induced neurotoxicity by alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum.

Abstract:

:Methamphetamine (METH) is a widely abused psychostimulant. Lactulose is a non-absorbable sugar, which effectively decreases METH-induced neurotoxicity in rat. However, the exact mechanisms need further investigation. In this study, 5-week-old male Sprague Dawley rats received METH (15 mg/kg, 8 intraperitoneal injections, 12-h interval) or saline and received lactulose (5.3 g/kg, oral gavage, 12-h interval) or vehicle 2 days prior to the METH administration. Compared to the control group, in the METH alone group, cytoplasmic vacuolar degeneration in hepatocytes, higher levels of alanine transaminase, aspartate transaminase and ammonia, overproduction of reactive oxygen species (ROS) and increase of superoxide dismutase activity in the blood were observed. Moreover, in rat striatum, expressions of nuclear factor erythroid 2-relatted factor-2 (Nrf2) and heme oxygenase-1 were suppressed in the nucleus, although over-expression of Nrf2 were observed in cytoplasm. Over-expressions of BECN1 and LC3-II indicated initiation of autophagy, while overproduction of p62 might suggest deficient autophagic vesicle turnover and impaired autophagy. Furthermore, accumulation of p62 cloud interact with Keap1 and then aggravate cytoplasmic accumulation of Nrf2. Consistently, over-expressions of cleaved caspase 3 and poly(ADP-ribose) polymerase-1 suggested the activation of apoptosis. The pretreatment with lactulose significantly decreased rat hepatic injury, suppressed hyperammonemia and ROS generation, alleviated the impaired autophagy in striatum, rescued the antioxidant system and repressed apoptosis. Taken together, with decreased blood ammonia, lactulose pretreatment reduced METH-induced neurotoxicity through alleviating the impaired autophagy, stabilizing the perturbed antioxidant system and suppressing apoptosis in rat striatum.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Xie XL,He JT,Wang ZT,Xiao HQ,Zhou WT,Du SH,Xue Y,Wang Q

doi

10.1016/j.toxlet.2018.03.015

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

107-113

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(18)30102-4

journal_volume

289

pub_type

杂志文章
  • Urinary trehalase activity and renal brush-border damage in inhabitants of a cadmium-polluted area (Jinzu River basin).

    abstract::Elevated urinary trehalase activity was observed in the inhabitants of the Jinzu River basin. Urinary trehalase activity was correlated with other urinalysis components, such as beta 2-microglobulin, glucose, amino nitrogen, and cadmium, of which a high level was observed in cadmium-polluted areas as compared with the...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(86)90206-7

    authors: Nakano M,Aoshima K,Katoh T,Teranishi H,Kasuya M

    更新日期:1986-12-01 00:00:00

  • Aloe emodin induces hepatotoxicity by activating NF-κB inflammatory pathway and P53 apoptosis pathway in zebrafish.

    abstract::The aim of this study was to investigate the hepatotoxic effect and its underlying mechanism of aloe emodin (AE). AE was docked with the targets of NF-κB inflammatory pathway and P53 apoptosis pathway respectively by using molecular docking technique. To verify the results of molecular docking and further investigate ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.02.007

    authors: Quan Y,Gong L,He J,Zhou Y,Liu M,Cao Z,Li Y,Peng C

    更新日期:2019-05-15 00:00:00

  • A mixture of routinely encountered xenobiotics induces both redox adaptations and perturbations in blood and tissues of rats after a long-term low-dose exposure regimen: The time and dose issue.

    abstract::Exposure of humans to xenobiotic mixtures is a continuous state during their everyday routine. However, the majority of toxicological studies assess the in vivo effects of individual substances rather than mixtures. Therefore, our main objective was to evaluate the impact of the 12- and 18-month exposure of rats to a ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.09.015

    authors: Fountoucidou P,Veskoukis AS,Kerasioti E,Docea AO,Taitzoglou IA,Liesivuori J,Tsatsakis A,Kouretas D

    更新日期:2019-12-15 00:00:00

  • α-asarone induces cardiac defects and QT prolongation through mitochondrial apoptosis pathway in zebrafish.

    abstract::α-asarone is a natural phenylpropene found in several plants, which are widely used for flavoring foods and treating diseases. Previous studies have demonstrated that α-asarone has many pharmacological functions, while some reports indicated its toxicity. However, little is known about its cardiovascular effects. This...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2020.02.003

    authors: Shang X,Ji X,Dang J,Wang L,Sun C,Liu K,Sik A,Jin M

    更新日期:2020-05-15 00:00:00

  • Effects of toxic doses of urethane on rat liver and lung microsomes.

    abstract::Administration of carcinogenic doses of urethane to male rats (for 30 days) and to females (for 45 days) caused degranulation of microsomes of livers and lungs to approx. 15 and 35%, respectively. The cholesterol levels also declined more than 50% in urethane-treated rats when compared with controls. Studies on struct...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(83)90170-4

    authors: Renuka,Dani HM

    更新日期:1983-01-01 00:00:00

  • Stimulation of DNA synthesis after a single administration of cadmium nitrate.

    abstract::The effect of a single intravenous (i.v.) injection of cadmium nitrate was investigated in livers of male Wistar rats. A significant increase in liver weight, accompanied by an elevation of total hepatic DNA content was observed. DNA synthesis as measured by the incorporation of [3H]thymidine, was found to be 6 times ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(84)90020-1

    authors: Ledda-Columbano GM,Columbano A,Coni PP,Vargiu M,Liguori C,Pani P

    更新日期:1984-12-01 00:00:00

  • Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways.

    abstract::In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2008.03.001

    authors: Kleinman MT,Araujo JA,Nel A,Sioutas C,Campbell A,Cong PQ,Li H,Bondy SC

    更新日期:2008-05-05 00:00:00

  • The role of NF-κB signaling pathway in polyhexamethylene guanidine phosphate induced inflammatory response in mouse macrophage RAW264.7 cells.

    abstract::Polyhexamethylene guanidine (PHMG) phosphate is a competitive disinfectant with strong antibacterial activity. However, epidemiologists revealed that inhaled PHMG-phosphate may increase the risk of pulmonary fibrosis associated with inflammation, resulting in the deaths of many people, including infants and pregnant w...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2015.01.005

    authors: Kim HR,Shin DY,Chung KH

    更新日期:2015-03-04 00:00:00

  • A murine model for assessing the respiratory hypersensitivity potential of chemical allergens.

    abstract::Using equimolar quantities of 2 chemical allergens, toluene diisocyanate (TDI), noted for its ability to cause respiratory hypersensitivity, and dinitrochlorobenzene (DNCB), noted for its dermal sensitizing activity, the mouse was evaluated as a possible model to indicate respiratory hypersensitivity. A previously pub...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(94)03234-x

    authors: Satoh T,Kramarik JA,Tollerud DJ,Karol MH

    更新日期:1995-06-01 00:00:00

  • Effects of collected road dusts on cell viability, inflammatory response, and oxidative stress in cultured human corneal epithelial cells.

    abstract::Most studies on the adverse effects of air pollution have focused on respiratory and cardiovascular diseases, and there are relatively few studies on eye diseases following exposure of ambient particulate matter (PM). Epidemiological and clinical researches correlating the eye and PMs have recently received attention....

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2017.12.012

    authors: Yoon S,Han S,Jeon KJ,Kwon S

    更新日期:2018-03-01 00:00:00

  • Human eosinophils are direct targets to nanoparticles: Zinc oxide nanoparticles (ZnO) delay apoptosis and increase the production of the pro-inflammatory cytokines IL-1β and IL-8.

    abstract::Zinc oxide NPs (ZnO) have been recently proposed as novel candidates for the treatment of allergic inflammatory diseases. Paradoxically, recent data suggested that ZnO could cause eosinophilic airway inflammation in rodents. Despite the above observations, there are currently no studies reporting direct interaction be...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2016.07.020

    authors: Silva LR,Girard D

    更新日期:2016-09-30 00:00:00

  • Predicted drug-induced bradycardia related cardio toxicity using a zebrafish in vivo model is highly correlated with results from in vitro tests.

    abstract::Several in vivo and in vitro studies have assessed methods of evaluating the cardio toxicity of compounds during drug development due to its importance for predicting human toxicity. However, in vivo/in vitro relationships have not yet been reported using a zebrafish model. This study determined the bradycardia of 15 ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2012.10.018

    authors: Park MJ,Lee KR,Shin DS,Chun HS,Kim CH,Ahn SH,Bae MA

    更新日期:2013-01-10 00:00:00

  • Screening of chiral shift reagents suitable to generically separate the enantiomers of V-agents by 31P-NMR spectroscopy.

    abstract::Fourteen amino acids protected at the N-terminal and at their side chains were screened for resolving the enantiomers of V-agents by NMR. While none of the shift reagents tested showed really effective separation in proton NMR, two of them (BOC-Gln(Xan)-OH, 16, and Z-Arg(Z)2-OH), 21, with 16 superior to 21) were found...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.12.004

    authors: Koller M,Thiermann H,Worek F

    更新日期:2020-03-01 00:00:00

  • Correlation between in vitro and in vivo models of proconvulsive activity with the carbapenem antibiotics, biapenem, imipenem/cilastatin and meropenem.

    abstract::The present study evaluated the proconvulsant liability of biapenem, a novel carbapenem antibiotic, in in vitro and in vivo experiments, in comparison with the carbapenems, imipenem/cilastatin and meropenem. Imipenem/cilastatin is a carbapenem antibiotic with known proconvulsive liability in man and in animal experime...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(95)80008-2

    authors: Day IP,Goudie J,Nishiki K,Williams PD

    更新日期:1995-04-01 00:00:00

  • Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma-bearing mice: protective role of heme oxygenase.

    abstract::Changes in the activities of antioxidant enzymes superoxide dismutase, catalase (CAT), glutathione peroxidase and heme oxygenase (HO) and changes in lipid peroxidation and reduced glutathione (GSH) levels were measured in the livers of control and Lewis lung carcinoma (LLC)-bearing mice 24 h after a single injection o...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(02)00416-2

    authors: Christova TY,Gorneva GA,Taxirov SI,Duridanova DB,Setchenska MS

    更新日期:2003-03-03 00:00:00

  • XPF plays an indispensable role in relieving silver nanoparticle induced DNA damage stress in human cells.

    abstract::Due to the specific antimicrobial activity of silver nanoparticles (AgNPs), they are widely used in wound dressings, coatings in medical devices and household products. In spite of the well-documented genotoxicity of AgNPs, the molecular mechanisms of relieving AgNP-induced DNA damage stress remain poorly understood. ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2018.02.022

    authors: Wang D,Yang H,Zhou Z,Zhao M,Chen R,Reed SH

    更新日期:2018-05-15 00:00:00

  • Upper respiratory tract nociceptor stimulation and stress response following acute and repeated Cyfluthrin inhalation in normal and pregnant rats: Physiological rat-specific adaptions can easily be misunderstood as adversities.

    abstract::This paper reviews the results from past regulatory and mechanistic inhalation studies in rats with the type II pyrethroid Cyfluthrin. Apart from many chemical irritants, Cyfluthrin was shown to be a neuroexcitatory agent without any inherent tissue-destructive or irritant property. Thus, any Cyfluthrin-induced neuroe...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.toxlet.2017.10.003

    authors: Pauluhn J

    更新日期:2018-01-05 00:00:00

  • Influence of polyaminocarboxylic acids on the removal of manganese-54 from the body organs of sham-operated and partially hepatectomized rats.

    abstract::EDTA, 1,2-cyclohexylenediamine tetra-acetic acid (CDTA), hexamethylene 1,6-diamine N,N,N',N'-tetra-acetic acid (HDTA), diethylene-triamine pentaacetic acid (DTPA) and nitrilotriacetic acid (NTA) were examined for the removal of manganese-54(54Mn) from some organs of sham-operated and partially hepatectomized rats in e...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(84)90037-7

    authors: Kaur G,Srivastava UC,Dwivedi RS,Srivastava RC

    更新日期:1984-07-01 00:00:00

  • A keratin 18 transgenic zebrafish Tg(k18(2.9):RFP) treated with inorganic arsenite reveals visible overproliferation of epithelial cells.

    abstract::Inorganic arsenic has strong human carcinogenic potential, but the availability of an animal model to study toxicity is extremely limited. Here, we used the transgenic zebrafish line Tg(k18(2.9):RFP) as an animal model to study arsenite toxicity. This line was chosen because the red fluorescent protein (RFP) is expres...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2005.10.024

    authors: Wang YH,Chen YH,Wu TN,Lin YJ,Tsai HJ

    更新日期:2006-06-01 00:00:00

  • Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke.

    abstract::Cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in China. However, lack of appropriate animal model slows down the progress in understanding pathogenesis of the disease. The aim of current study is to establish and evaluate a more adequate rat model...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2009.06.850

    authors: Zheng H,Liu Y,Huang T,Fang Z,Li G,He S

    更新日期:2009-09-28 00:00:00

  • Neurochemical effects of ethylhexyl nitrate in rats.

    abstract::Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 +/- 15.8 micrograms nitrite/h X kg body wt. was detected between 5-24 h. Cerebral glutathione concentration was below the co...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(83)90281-3

    authors: Someroja S,Savolainen H

    更新日期:1983-10-01 00:00:00

  • An antimicrotubule agent, TZT-1027, does not induce neuropathologic alterations which are detected after administration of vincristine or paclitaxel in animal models.

    abstract::One of the major dose-limiting toxicities induced by antimicrotubule antitumor agents such as vinca alkaloids and taxanes is peripheral neuropathy. The neurotoxicity of TZT-1027 (a dolastatin 10 derivative antimicrotubule agent) was thus assessed using the animal models for antimicrotubule agent-induced neurotoxicity....

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(01)00327-7

    authors: Ogawa T,Mimura Y,Isowa K,Kato H,Mitsuishi M,Toyoshi T,Kuwayama N,Morimoto H,Murakoshi M,Nakayama T

    更新日期:2001-04-30 00:00:00

  • Endocrine effects of hexabromocyclododecane (HBCD) in a one-generation reproduction study in Wistar rats.

    abstract::The brominated flame retardant (BFR) hexabromocyclododecane was tested in a one-generation reproduction assay in Wistar rats, enhanced for endocrine parameters. A solution of the compound in corn oil was mixed in the feed, targeting at dietary exposure of 0-0.1-0.3-1-3-10-30-100 mg/kg body weight/day (mkd) in parental...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2008.12.003

    authors: van der Ven LT,van de Kuil T,Leonards PE,Slob W,Lilienthal H,Litens S,Herlin M,Håkansson H,Cantón RF,van den Berg M,Visser TJ,van Loveren H,Vos JG,Piersma AH

    更新日期:2009-02-25 00:00:00

  • 5-Azacytidine prevents cisplatin induced nephrotoxicity and potentiates anticancer activity of cisplatin by involving inhibition of metallothionein, pAKT and DNMT1 expression in chemical induced cancer rats.

    abstract::5-Azactydine inhibits cell growth by direct cytotoxic action as well as by inhibition of DNA methyl transferase enzyme. Inhibitors of DNMT have been reported to potentiate the therapeutic activity of cisplatin in vitro. Dose dependent bone marrow toxicity, neurotoxicity and nephrotoxicity are the major side effects of...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2009.08.018

    authors: Tikoo K,Ali IY,Gupta J,Gupta C

    更新日期:2009-12-15 00:00:00

  • Curcumin ameliorates intrahepatic angiogenesis and capillarization of the sinusoids in carbon tetrachloride-induced rat liver fibrosis.

    abstract::Neoangiogenesis and the development of an abnormal angio-architecture in the liver are strongly linked with progressive fibrogenesis. This study aimed to evaluate the ability of curcumin to protect liver fibrosis-associated angiogenesis and capillarization of the sinusoids in experimental rats. Liver fibrosis was indu...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2013.06.240

    authors: Yao Q,Lin Y,Li X,Shen X,Wang J,Tu C

    更新日期:2013-09-12 00:00:00

  • Ototoxic and nephrotoxic drugs inhibit agonist-induced inositol phosphate formation in rat brain synaptoneurosomes.

    abstract::Neomycin (an aminoglycoside antibiotic), ethacrynate (a loop diuretic), cisplatin (an anticancer drug) and mercuric chloride are chemically unrelated drugs which present similar ototoxic and nephrotoxic properties. We have found that all these molecules inhibit inositol phosphate turnover induced by carbachol or gluta...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(90)90076-x

    authors: Guiramand J,Lenoir M,Pujol R,Récasens M

    更新日期:1990-05-01 00:00:00

  • Effects of novel 17β-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration.

    abstract::Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of A...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2020.12.012

    authors: Fišar Z,Musílek K,Benek O,Hroch L,Vinklářová L,Schmidt M,Hroudová J,Raboch J

    更新日期:2021-03-15 00:00:00

  • Ambient PM2.5 chronic exposure leads to cognitive decline in mice: From pulmonary to neuronal inflammation.

    abstract::Fine particulate matter 2.5 (PM2.5), one of the main components of air pollutants, seriously threatens human health. Possible neuronal dysfunction induced by PM2.5 has received extensive attention. However, there is little evidence for the specific biochemical mechanism of neuronal injury induced by PM2.5. Moreover, t...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2020.06.014

    authors: Shou Y,Zhu X,Zhu D,Yin H,Shi Y,Chen M,Lu L,Qian Q,Zhao D,Hu Y,Wang H

    更新日期:2020-10-01 00:00:00

  • Detection and quantitative determination of 3-nitropropionic acid in bovine urine.

    abstract::The separation and determination of 3-nitropropionic acid (NPA) in bovine urine by reverse-phase HPLC is described. The method utilizes a rapid ethyl acetate extraction and this clean-up step also improves the chromatographic resolution of NPA in bovine plasma. A simple colorimetric method is also developed for the ra...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(90)90013-c

    authors: Majak W,McDiarmid RE

    更新日期:1990-02-01 00:00:00

  • Chemicals and proteins as allergens and adjuvants.

    abstract::Small molecular weight chemicals may irritate tissues via the induction of the production of various proinflammatory and chemotactic molecules. The structure of these irritants is heterogenous, as is the pattern of their effects. Chemicals are potentially allergenic (i.e. haptens) when they are able to bind proteins s...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/0378-4274(96)03676-4

    authors: Kapsenberg ML

    更新日期:1996-08-01 00:00:00