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• W2920084851 abstract "Human population is constantly exposed to health risks by exposure to chemicalsbelonging to various classes such as pesticides, pollutants and chemicals used inagriculture, food industries etc. It is important to keep use of such chemicals undercontinuous observation and their effects must be re-evaluated in the light of changingconditions of use and new scientific information (Council directive 89/107/EEC).Major part of my thesis is focused on investigating toxic effects and mechanisms ofaction of one such environmental pollutant, glyphosate, a non-selective herbicide. Inthis thesis, mechanistic toxicology of sodium benzoate (SB), a common foodpreservative, has also been investigated. I have used zebrafish vertebrate animalmodel for toxicity studies included in my thesis and therefore I have also establisheda zebrafish research lab at IITH.Glyphosate is a non-selective herbicide. Results included in my thesis indicatesignificant acute toxicity in zebrafish embryos exposed to glyphosate concentrations50 µg/mL and above. LD50 for glyphosate was calculated to be 66.04 ± 4.6 µg/mLafter 48 hours of exposure. Developmental toxicity due to glyphosate was alsoobserved as physical malformations in zebrafish embryos such as yolk sac edema,pericardial edema, body bending and eye defects. Glyphosate induced cardiotoxicityabove 50 µg/mL concentrations as indicated by reduced heartbeat of zebrafishembryos in a dose and time dependent manner. To analyze heartbeat, we developeda simple yet powerful method of heartbeat analysis from the untethered,unanesthetized and unlabeled zebrafish larva using ImageJ (open-source)software. We named our semi-automatic method as ZebraPace for Zebrafish PreciseAlgorithm for Cardiac-rhythm Estimation. Our method is truly cost-effective, usesalgorithm which involves fewer steps without the requirement of cumbersome imageprocessing and programming steps. It is also highly reproducible across researchers.The decrease in the heartbeat of zebrafish embryos upon exposure to glyphosate wasaccompanied by a reduction in the gene expression of cacna1c (L-type calciumchannel) and ryr2a (Ryanodine receptor) indicating alterations in the proteinsinvolved in excitation-contraction coupling and calcium signaling. A change incalcium signaling upon glyphosate exposure was also evident by the upregulation of hspb11 gene (heat shock protein) in our experiments. Of note, hspb11 has been usedas a marker to detect changes in cytosolic calcium. Therefore, taken together ourresults indicate that glyphosate may be inducing cardiotoxicity by changes incalcium signaling. In addition, in our experiments, glyphosate reduced the generationof nitric oxide (NO). NO signaling and calcium signaling are tightly linked and anyalteration in one will lead to changes in the other.Glyphosate exposure to adult zebrafish resulted in a reduced reproduction potentialindicated by less number of successful mating between treated zebrafish. We observeddevelopmental defects and cardiotoxicity in the progeny of adult zebrafish exposed toglyphosate at a concentration of 10 µg/mL. It is important to note that, the obtainedprogeny was not exposed to glyphosate. Taken together, these results indicate thatglyphosate induced toxicity can be carried to the next generation. Swimmingbehaviour was also affected in adult zebrafish exposed to glyphosate at aconcentration of 10 µg/mL. The speed of swimming was increased which wasinterrupted with long durations of freezing in between as compared to control adultfishes. Treated adult zebrafish also showed anxiety-like behaviour as indicated byreduced exploration of the center of the open field test tank.I have also investigated mechanistic toxicology of SB. Results included in my thesisindicate that SB induced biochemical (oxidative stress) and behavioural (anxiety-likebehaviour) abnormalities in developing zebrafish larva. LD50 of SB induced toxicitywas approximately 400 ppm after 48 hours of SB exposure. Our data strongly supportsharmful effects of SB at increasing doses and suggests caution in the excessive use ofthis preservative in processed and convenience foods.Overall, results in my thesis indicate that both glyphosate and SB can causesignificant toxicity and we suggest caution in the excessive use of chemicals whichhave the potential to cause toxicity." @default.
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• W2920084851 date "2019-01-01" @default.
• W2920084851 modified "2023-10-15" @default.
• W2920084851 title "Investigation of Toxicity Induced by Chemicals and TheirMechanisms using Zebrafish Vertebrate Animal Model" @default.
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