d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions.

Abstract:

:Cataract is the leading cause of blindness with an estimated 16 million people affected worldwide. d-galactose (d-gal) is a reducing sugar that widely distributed in foodstuffs, and studies show that d-gal could promote cataract formation by damaging nature lens epithelial cells (LECs). However, the underlying mechanism is unclear. In our present study, d-gal resulted in premature senescence of LECs, which was confirmed by determining the β-galactosidase activity, cell proliferative potential and cell cycle distribution, though apoptosis of LECs was not observed. We also verified that d-gal induced the impairment of autophagy flux by measuring the expression of LC3II and P62. Meanwhile, we found that d-gal induced mitochondrial dysfunctions of LECs through increasing reactive oxygen species (ROS), reducing ATP synthesis and mitochondrial potential (MMP), enhancing the concentration of cytoplasm Ca2+ and permeability transition pore (mPTP) opening. Metformin, as a potential anti-aging agent, suppressed the senescence of LECs by restoring autophagy flux and mitochondria functions. Nevertheless, the antioxidant N-acetylcysteine (NAC) scavenged ROS significantly but was not efficient in preventing LECs from premature senescence. Our data suggests that restoring autophagy activity and improving mitochondrial functions may be a potential strategy for the prevention of LECs senescence-related cataract.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Xu Y,Li Y,Ma L,Xin G,Wei Z,Zeng Z,Xing Z,Li S,Niu H,Huang W

doi

10.1016/j.toxlet.2018.02.001

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

99-106

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(18)30039-0

journal_volume

289

pub_type

杂志文章
  • Biochemical changes in the rat cerebellar cortex elicited by chronic treatment with methyl mercury.

    abstract::Long-term (20 days) treatment with methyl mercury (MeHg) increases the total number of benzodiazepine binding sites and decreases essentially the content of cyclic GMP in the cerebellar cortex. In contrast, this treatment fails to modify the content of GABA and cyclic AMP, GAD activity and GABA binding sites in the sa...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(83)90066-8

    authors: Concas A,Corda MG,Salis M,Mulas ML,Milia A,Corongiu FP,Biggio G

    更新日期:1983-08-01 00:00:00

  • Chromosomal aberrations and in vitro radiosensitivity: intra-individual versus inter-individual variability.

    abstract::In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3....

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2003.12.044

    authors: Vral A,Thierens H,Baeyens A,De Ridder L

    更新日期:2004-04-01 00:00:00

  • Is the acceptable daily intake as presently used an axiom or a dogma?

    abstract::International scientific committees, regional scientific committees such as those of the European Union, and national regulatory agencies generally use the uncertainly factor approach for establishing acceptable or tolerable intakes of substances that exhibit thresholds of toxicity. No observed adverse effect levels (...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.toxlet.2008.06.003

    authors: Galli CL,Marinovich M,Lotti M

    更新日期:2008-08-15 00:00:00

  • Effect of a low-dose endotoxin pretreatment on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine in rats.

    abstract::The effect of endotoxin pretreatment (1 mg/kg body weight, i.p., once daily for 2 days) on the gastric mucosal damage induced by aspirin, phenylbutazone and reserpine has been studied in albino rats. When given alone, endotoxin did not produce any visibly discernible gastric lesions. It produced a significant augmenta...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(87)90168-8

    authors: Tariq M

    更新日期:1987-06-01 00:00:00

  • Urinary mutagenicity after controlled exposure to environmental tobacco smoke (ETS).

    abstract::20 non-smokers on a defined diet low in polycyclic aromatic hydrocarbons (PAH) were exposed to environmental tobacco smoke (ETS) in an unventilated room for 8 h. The urinary mutagenicity in the 24-h urine samples as tested with the Salmonella (TA98) microsome assay did not significantly increase after exposure to eith...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(87)90098-1

    authors: Scherer G,Westphal K,Biber A,Hoepfner I,Adlkofer F

    更新日期:1987-01-01 00:00:00

  • Effect of paraquat on lung calcium transport.

    abstract::The effect of paraquat on lung subcellular calcium transport was studied in male Sprague-Dawley rats. With a high dose of 30 mg/kg given i.p., a significant decrease in the lung mitochondrial and microsomal calcium uptake at 24, 48, and 72 h after paraquat was observed. Trend of recovery was evident at 96 h in the sur...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(88)90117-8

    authors: Agarwal AK,Coleman JW

    更新日期:1988-09-01 00:00:00

  • In vitro effect of aflatoxin B1 on rat liver macrophages (Kuffer cells).

    abstract::The effect of aflatoxin B1 on the uptake and incorporation of [3H]leucine and [3H]uridine and on phagocytosis of latex particles was studied using cultures of rat liver macrophages (Kuffer cells). Aflatoxin B1 inhibited the incorporation of both isotopes, but inhibition of uridine incorporation was greater than that o...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(85)90039-6

    authors: Mohapatra NK,Roberts JF

    更新日期:1985-12-01 00:00:00

  • Epidemiological application of early markers of nephrotoxicity.

    abstract::This paper is a review of epidemiological studies in which sensitive markers of nephrotoxicity have been used to detect the early effects of chemicals on the kidney. Most of the studies are cross-sectional, and their objective was either to identify potentially nephrotoxic chemicals (organic solvents, heavy metals) in...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(89)90137-9

    authors: Bernard A,Lauwerys R

    更新日期:1989-03-01 00:00:00

  • Quantitative perspectives on behavioral toxicology.

    abstract::Behavioral endpoints offer special challenges to toxicology. One arises from the sometimes conflicting ways in which adverse effects may be expressed. For example, both increases and decreases in response rates of schedule-controlled performance may be produced by a specific agent, depending on the specific schedule. ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(88)90034-3

    authors: Weiss B

    更新日期:1988-10-01 00:00:00

  • LLU-alpha, an endogenous metabolite of gamma-tocopherol, is more effective against metal nephrotoxicity in rats than gamma-tocopherol.

    abstract::Antioxidants of the vitamin E family have protective effects against metal toxicity. We examined the protective effect of racemic LLU-alpha [2,7,8-trimethyl-2-(carboxyethyl)-6-hydroxychroman] a metabolite of gamma-tocopherol, in comparison to the effect of alpha- and gamma-tocopherol in rats treated with sodium dichro...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(01)00368-x

    authors: Appenroth D,Karge E,Kiessling G,Wechter WJ,Winnefeld K,Fleck C

    更新日期:2001-07-06 00:00:00

  • JNK and p38 MAPK regulate oxidative stress and the inflammatory response in chlorpyrifos-induced apoptosis.

    abstract::To investigate mechanisms of neuronal cell death in response to chlorpyrifos (CPF), a pesticide, we evaluated the regulation of ROS and COX-2 in human neuroblastoma SH-SY5Y cells treated with CPF. CPF treatment produced cytotoxic effects that appeared to involve an increase in ROS. In addition, CPF treatment activated...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2013.02.003

    authors: Ki YW,Park JH,Lee JE,Shin IC,Koh HC

    更新日期:2013-04-26 00:00:00

  • Radiolabelled soman binding to sera from Rats, Guinea Pigs and Monkeys.

    abstract::Soman is a highly toxic organophosphorus chemical warfare compound that binds rapidly and irreversibility to a variety of serine active enzymes, i.e., butyryl- and acetyl-cholinesterases and carboxylesterase. The in vivo toxicity of soman has been reported to vary significantly in different animal species, such as rat...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2017.11.016

    authors: Lenz DE,Cerasoli D,Maxwell DM

    更新日期:2018-02-01 00:00:00

  • Toxic effects of mosquito coil (a mosquito repellent) smoke on rats. II. Morphological changes of the respiratory system.

    abstract::A group of 20 female albino rats was exposed to mosquito coil smoke, 8 h a day, 6 days per week, for 60 days. An additional group receiving air exposure served as control. The smoke-exposed animals had a lower body weight than the controls. Smoke-induced histopathological lesions, including an inflammation of the trac...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(87)90238-4

    authors: Liu WK,Wong MH

    更新日期:1987-12-01 00:00:00

  • A novel in vivo model for predicting myelotoxicity of chemotherapeutic agents using IL-3/GM-CSF transgenic humanized mice.

    abstract::Evaluating myelotoxicity is essential for ensuring the safety of novel drugs before they are approved for clinical applications. Although in vivo prediction of the maximum tolerated doses (MTDs) of anticancer drugs is usually performed in rodents, the results are not always applicable to clinical treatment because dru...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2017.09.013

    authors: Ito R,Nagai D,Igo N,Okuda Y,Sekine K,Ichimura E,Katano I,Mizushima T,Goto M,Ohnishi Y,Ito M,Okamoto K

    更新日期:2017-11-05 00:00:00

  • Vinyl acetate induces intracellular acidification in mouse oral buccal epithelial cells.

    abstract::Vinyl acetate exposure in drinking water has been associated with tumor formation in the upper gastrointestinal tract of rats and mice. One potential mechanism for inducing carcinogenesis involves acidification of the intracellular environment due to the metabolism of vinyl acetate to acetic acid. Prolonged intracellu...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2005.03.002

    authors: Nakamoto T,Wagner M,Melvin JE,Bogdanffy MS

    更新日期:2005-08-14 00:00:00

  • Indirect human exposure to pharmaceuticals via drinking water.

    abstract::There are numerous observations of pharmaceuticals (or their metabolites) as contaminants in wastewater, surface water and groundwater. This implies a potential for indirect human exposure to pharmaceuticals via drinking water supplies. Various effect benchmarks may be employed in an evaluation of the significance of ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(03)00071-7

    authors: Webb S,Ternes T,Gibert M,Olejniczak K

    更新日期:2003-05-15 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

  • Stem Leydig cell regeneration in the adult rat testis is inhibited after a short-term triphenyltin exposure.

    abstract::Triphenyltin (TPT) is an organotin compound and may be an endocrine disruptor, impairing the male reproductive system. However, the effect of short-term TPT exposure on stem Leydig cell regeneration later on remains unknown. Here, we show that TPT affects stem Leydig cell regeneration in the adult rat testis. Adult ma...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.02.010

    authors: Ni C,Fang Y,Chen X,Wu K,Li H,Wang Y,Zhenkun L,Lian Q,Ge RS

    更新日期:2019-05-15 00:00:00

  • Airway responses during and directly after single-time exposure to ozone.

    abstract::Breathing pattern and lung mechanical parameters were measured in 7 female Wistar rats (ca. 200 g) during exposure to 1.0 (n = 5) or 1.3 (n = 2) ppm ozone in air for 2 h and during a 2-h post-exposure observation period. Changes in breathing pattern showed a gradual decrease from 3 to 2 Hz at constant minute ventilati...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(94)90036-1

    authors: Zwart A,Arts JH

    更新日期:1994-06-01 00:00:00

  • The effect of α-synuclein and Tau in methamphetamine induced neurotoxicity in vivo and in vitro.

    abstract::The upregulated α-synuclein (α-syn) and Tau co-occur in methamphetamine (METH) abusers' brains. Here, we designed experiments mainly to investigate whether α-syn and Tau interact in METH exposure. We detected the expression of α-syn, total Tau, and phosphorylation of Tau at Serine 396 (pSer396 Tau) under in vitro and ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.11.028

    authors: Ding J,Lian Y,Meng Y,He Y,Fan H,Li C,Qiu P

    更新日期:2020-02-01 00:00:00

  • Embryonic toxicity of sanguinarine through apoptotic processes in mouse blastocysts.

    abstract::In this study, we examined the cytotoxic effects of sanguinarine, a phytoalexin with antimicrobial, anti-oxidant, anti-inflammatory and pro-apoptotic effects, on the blastocyst stage of mouse embryos, subsequent embryonic attachment and outgrowth in vitro and in vivo implantation via embryo transfer. Blastocysts treat...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2011.06.018

    authors: Chan WH

    更新日期:2011-09-10 00:00:00

  • Urinary metabolites of furan in waterpipe tobacco smokers compared to non-smokers in home settings in the US.

    abstract:OBJECTIVES:Determine uptake of furan, a potential human carcinogen, in waterpipe tobacco (WPT) smokers in home settings. METHODS:We analysed data from a US convenience sample of 50 exclusive WPT smokers, mean age 25.3 years, and 25 non-smokers, mean age 25.5 years. For WPT smokers, data were collected at a home visit ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2020.08.002

    authors: Kassem NOF,Peterson LA,Liles S,Kassem NO,Zaki FK,Lui KJ,Vevang KR,Dodder NG,Hoh E,Hovell MF

    更新日期:2020-10-15 00:00:00

  • Cytokine production by co-cultures exposed to monodisperse amorphous silica nanoparticles: the role of size and surface area.

    abstract::The aim of this study was to test the influence of nanoparticle size and surface area (SA) on cytokine secretion by co-cultures of pulmonary epithelial cells (A549), macrophages (differentiated THP-1 cells) and endothelium cells (EA.hy926) in a two-compartment system. We used monodisperse amorphous silica nanoparticle...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2012.03.002

    authors: Napierska D,Thomassen LC,Vanaudenaerde B,Luyts K,Lison D,Martens JA,Nemery B,Hoet PH

    更新日期:2012-06-01 00:00:00

  • The effect of cyclohexylamine on the embryo following oral administration to mice and rats.

    abstract::The possible embryotoxic effects of cyclohexylamine hydrochloride doses (expressed as free base) of 10, 30 and 100 mg/kg of body weight per day administered orally in water to mice and rats from the 6th to 15th day post-coitum were investigated. Treatment with daily doses of up to 100 mg/kg of body weight to mice and ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(83)90049-8

    authors: Lorke D,Machemer L

    更新日期:1983-06-01 00:00:00

  • Effect of acute and repeated chlordimeform treatment on rat hepatic microsomal drug metabolizing enzymes.

    abstract::The effect of chlordimeform (CDM) treatment on the hepatic microsomal drug metabolizing enzymes was examined in male and female rats following either acute or repeated treatment. After acute administration of chlordimeform (100 mg/kg, i.p., 1 hour before killing) differential effects were observed in various parameter...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(83)90072-3

    authors: Budris DM,Yim GK,Carlson GP,Schnell RC

    更新日期:1983-08-01 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

  • Predictive testing for respiratory sensitisation.

    abstract::A rat bioassay has been developed to provide an objective approach for the identification and classification of upper and lower respiratory tract irritants, with particular emphasis on the concentration-dependent induction and regression of lesions characteristic of asthma, such as persisting non-specific airway hyper...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/0378-4274(96)03688-0

    authors: Pauluhn J

    更新日期:1996-08-01 00:00:00

  • Differential immunotoxic effects of inorganic and organic mercury species in vitro.

    abstract::Despite the fact that humans are exposed to multiple forms of mercury (elemental, inorganic, and organic), most research on mercury toxicity has focused on methylmercury (MeHg) and on neurotoxic outcomes and mechanisms. Recent work has indicated that the immunotoxic effects of mercury compounds may be significant cont...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2010.06.015

    authors: Gardner RM,Nyland JF,Silbergeld EK

    更新日期:2010-10-05 00:00:00

  • Benzodiazepines medazepam and midazolam are activators of pregnane X receptor and weak inducers of CYP3A4: investigation in primary cultures of human hepatocytes and hepatocarcinoma cell lines.

    abstract::Benzodiazepines have wide-spread used in pharmacotherapy for their anxiolytic, myorelaxant, hypnotic, amnesic and anticonvulsive properties. Despite benzodiazepines are used in clinics over 50 years, they have not been surprisingly tested for capability to induce major drug-metabolizing cytochromes P450. In the curren...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2010.01.004

    authors: Vrzal R,Kubesova K,Pavek P,Dvorak Z

    更新日期:2010-03-15 00:00:00

  • A repeated dose study of the toxicity of CR applied to the skin of mice.

    abstract::Dibenz (b,f)-1-4 oxazepine (CR) was applied to the skin of C3H and Porton-strain mice, daily for 12 weeks. After a further 80 weeks the animals were sacrificed and examined grossly and histologically. The results were compared with appropriate solvent and untreated controls. No abnormalities were found that could be a...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:

    authors: Marrs TC,Gray MI,Colgrave HF,Gall D

    更新日期:1982-10-01 00:00:00