Neurotoxicological effects induced by up-regulation of miR-137 following triclosan exposure to zebrafish (Danio rerio)

Liu, Jinfeng; Xiang, Chenyan; Huang, Wenhao; Mei, Jingyi; Sun, Liankun; Ling, Yuhang; Wang, Caihong; Wang, Xuedong; Dahlgren, Randy A.; Wang, Huili

doi:10.1016/j.aquatox.2018.11.017

Cited by 19 publications

(8 citation statements)

References 47 publications

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“…These studies also reported dose dependent increase in mortality and bioaccumulation of TCS in the organisms. Because of lipophilicity, TCS has the potential for bioaccumulation in the food web 9 and is considered to be hazardous for the environment and life even at low concentration. Destructive impacts of TCS on aquatic organisms include, endocrine disruption 10 , neurotoxicity 11 , mitochondrial dysfunction 12 , oxidative stress due to increased production of various reactive oxygen species (ROS), alteration of the activity of antioxidative, detoxification and metabolic enzymes and impairment of immune system 13 – 17 .…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps

Dar

Sharma

Singh

et al. 2020

Sci Rep

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Accumulation, contents of protein, non-enzymatic antioxidant glutathione (GSH and GSSG), lipid peroxidation product (melondialdehyde-MDA) and organic acids (fumarate, succinate, malate and citrate), and activities of neurological (acetylcholinesterase-AChE), detoxification (glutathione S-transferase-GST) and metabolic (lactate dehydrogenase-LDH, aspartate transaminase-AST and alanine transaminase-ALT) enzymes were recorded in the hatchlings of Cyprinus carpio, Ctenopharyngodon idella, Labeo rohita and Cirrhinus mrigala after 7 and 14 days exposure and 10 days post exposure (recovery period) to sublethal concentrations (0.005, 0.01, 0.02 and 0.05 mg/L) of triclosan, a highly toxic and persistent biocide used in personal care products. Accumulation was maximum between 7–14 days at 0.01 mg/L for C. carpio and L. rohita but at 0.005 mg/L for C. idella and C. mrigala. No triclosan was observed at 0.005 mg/L in C. carpio and C. mrigala after recovery. Significant decline in protein, glutathione and acetylcholinesterase but increase in glutathione S-transferase, lactate dehydrogenase, aspartate transaminase, alanine transaminase, melondialdehyde and organic acids over control during exposure continued till the end of recovery period. Integrated biomarker response (IBR) analysis depicted higher star plot area for glutathione and glutathione S-transferase during initial 7 days of exposure, thereafter, during 7–14 days of exposure and the recovery period, higher star plot area was observed for acetylcholinesterase, aspartate transaminase, alanine transaminase and organic acids. Higher star plot area was observed for protein in all the species throughout the study. The study shows that L. rohita is most sensitive and glutathione, acetylcholinesterase, aspartate transaminase and alanine transaminase are the biomarkers for the toxicity of sublethal concentrations of TCS.

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Section: Introductionmentioning

confidence: 99%

Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps

Dar

Sharma

Singh

et al. 2020

Sci Rep

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“…Triclosan caused ventriculomegaly, a decrease in the neuronal cell count, formation of the glial scars accompanied by abnormal glial cell proliferation in adult zebrafish. [ 62 ] Hematoxylin and eosin staining of the adult zebrafish spinal cord displayed a decreased number of glial cells and altered fiber structures in triclosan‐treated groups. These changes induced hearing and vision abnormalities in the zebrafish.…”

Section: Triclosan Induced Neurotoxicitymentioning

confidence: 99%

“…Behavioral findings also established that both, induced overexpression of miR‐137 and triclosan exposure (which caused overexpression of miR‐137) contributed to hearing or vision impairment in zebrafish thus providing a unique mechanism for triclosan induced neurotoxicity. [ 62 ]…”

Section: Triclosan Induced Neurotoxicitymentioning

confidence: 99%

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Neurotoxic mechanisms of triclosan: The antimicrobial agent emerging as a toxicant

Pullaguri

Umale

Bhargava

2022

J Biochem & Molecular Tox

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Several scientific studies have suggested a link between increased exposure to pollutants and a rise in the number of neurodegenerative disorders of unknown origin. Notably, triclosan (an antimicrobial agent) is used in concentrations ranging from 0.3% to 1% in various consumer products. Recent studies have also highlighted triclosan as an emerging toxic pollutant due to its increasing global use. However, a definitive link is missing to associate the rising use of triclosan and the growing number of neurodegenerative disorders or neurotoxicity. In this article, we present systematic scientific evidence which are otherwise scattered to suggest that triclosan can indeed induce neurotoxic effects, especially in vertebrate organisms including humans. Mechanistically, triclosan affected important developmental and differentiation genes, structural genes, genes for signaling receptors and genes for neurotransmitter controlling enzymes. Triclosan-induced oxidative stress impacting cellular proteins and homeostasis which triggers apoptosis.Though the scientific evidence collated in this article unequivocally indicates that triclosan can cause neurotoxicity, further epidemiological studies may be needed to confirm the effects on humans.

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“…Microarray analysis showed that several aberrant miRs were greatly dysregulated in injured spinal cords at 4 h post IR (Figure 2A). Among these miRs, miR-137-3p has been indicated to be closely associated with neurodevelopment and CNS disease and to be highly expressed in the brain [30,33].…”

Section: Ir-induced Aberrant Spinal Mir-137-3p Expression and Negativmentioning

confidence: 99%

Roles of the miR-137-3p/CAPN-2 gene pair in ischemia-reperfusion-induced neuronal apoptosis through modulation of p35 cleavage and subsequent caspase-8 overactivation

Zhang

et al. 2019

Preprint

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Background: Neuron survival after ischemia-reperfusion (IR) injury is the primary determinant of motor function prognosis. MicroRNA (miR)-based gene therapy has gained attention. Our previous work explored the mechanisms by which miR-137-3p modulates neuronal apoptosis in both in vivo and in vitro IR models.Methods: IR-induced motor dysfunction and spinal calpain (CAPN) subtype expression and subcellular distribution were detected within 12 h post IR. Dysregulated miRs, including miR-137-3p, were identified by miR microarray analysis and confirmed by PCR. Luciferase assay confirmed that CAPN-2 is a corresponding target of miR-137-3p, and their modulation of motor function was evaluated by intrathecal infection with synthetic miRs. CAPN-2 activity was measured by the intracellular Ca2+ concentration and mean fluorescence intensity in vitro. Neuronal apoptosis was detected by flow cytometry and lactate dehydrogenase (LDH) release. The activities of p35, p25, Cdk5 and caspase-8 were evaluated by ELISA and Western blotting after transfection with specific inhibitors and miRs.Results: The IR-induced motor dysfunction time course was closely associated with CAPN-2 protein upregulation, which was mainly distributed in neurons. The miR-137-3p/CAPN-2 gene pair was confirmed by luciferase assay. miR-137-3p mimic significantly improved IR-induced motor dysfunction and decreased CAPN-2 expression, even in combination with recombinant rat calpain-2 (rr-CALP2) injection, whereas miR-137-3p inhibitor reversed these effects. Similar changes were observed in the intracellular Ca2+ concentration and CAPN-2 expression and activity when cells were exposed to OGD/R and transfected with synthetic miRs in vitro. Moreover, double fluorescence revealed that CAPN-2, p35, p25 and caspase-8 were all identically distributed in neurons. The decrease in CAPN-2 expression and activity was accompanied by the opposite changes in p35 activity and protein expression in cells transfected with miR-137-3p mimic, roscovitine (a Cdk5 inhibitor) or Z-IETD-FMK (a caspase-8 inhibitor). Correspondingly, more surviving neurons were observed with the abovementioned treatments, indicated by a decrease in apoptotic cell percentage, LDH release and p25, Cdk5, caspase-8 and caspase-3 protein expression.Conclusions: The miR-137-3p/CAPN-2 gene pair functions to modulate neuronal apoptosis during IR injury, possibly through CAPN-2 inhibition leading to p35 cleavage and inhibition of subsequent p25/Cdk5 and caspase-8 overactivation.

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Neurotoxicological effects induced by up-regulation of miR-137 following triclosan exposure to zebrafish (Danio rerio)

Cited by 19 publications

References 47 publications

Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps

Biomarkers for the toxicity of sublethal concentrations of triclosan to the early life stages of carps

Neurotoxic mechanisms of triclosan: The antimicrobial agent emerging as a toxicant

Roles of the miR-137-3p/CAPN-2 gene pair in ischemia-reperfusion-induced neuronal apoptosis through modulation of p35 cleavage and subsequent caspase-8 overactivation

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