Open Access
Subscription Access
Open Access
Subscription Access
Toxicological Sequelae of Pesticide Combinations Exposure in Buffalo Mesenchymal Stem Cells under In Vitro
Subscribe/Renew Journal
The presence of one or more pesticides in a variety of mediums is responsible for their indirect toxicological events leading to cell senescence. In the present investigation, the endeavor was made to see the effect of pesticides Car-Benda-Zim (CBZ) and IMIdacloprid (IMI) alone and in combination with bone marrow-derived Mesenchymal Stem Cells (bMSCs) of buffalo origin. Isolated and cultured bMSCs were exposed to CBZ and IMI alone and in combinations at lower doses. Cells were observed for alterations in cell morphology, oxidative stress, mitochondrial damage and cellular senescence. bMSCs characterized for stem cell surface markers and found to be positive for AP, CD73 and OCT4. bMSCs exposed to IC25, IC12.5 and IC6.25 CBZ and IMI alone and combinations of IC12.5 and IC6.25 of CBZ and IMI. Results revealed significant reduction (p≤0.05) in cell viability noticed on microscopic examination along with loss of normal cell morphology and increased in Reactive Oxygen Species (ROS) positive cells, cells with loss of ΔΨm and number of senescent cells in CBZ and IMI treated groups. Lower dose combination groups showed elevated effects when compared with higher dose alone treated groups and control groups. Present findings suggest that CBZ and IMI induced cytotoxicity in bMSCs mediated via ROS production, altered ΔΨm leading to the cell damage and predisposing senescence process. Moreover, the co-existence of CBZ and IMI in a medium has a considerably more toxic effect than their individual effect.
Keywords
Carbendazim, Imidacloprid, Stem Cells, Mitochondrial Transmemberane Potential, Reactive (ROS), Senescence
User
Subscription
Login to verify subscription
Font Size
Information
- Damalas CA, Koutroubas SD. Farmers’ Training on pesticide use is associated with elevated safety behavior. Toxics. 2017; 5(3):19. https://doi.org/10.3390/toxics5030019. PMID: 29051451; PMCID: PMC5634698.
- Patil N, Lonare M, Sharma M, Lalhriatpuia P, Saini S, Rampal S. Hemato-biochemical alterations mediated by carbendazim exposure and protective effect of quercetin in male rats. Toxicol Int. 2018; 25(1):1-12. https://doi:10.22506/ti/2018/v25/i1/21569.
- Çevik UA, Sağlık BN, Korkut B, Özkay Y, Ilgın S. Antiproliferative, cytotoxic, and apoptotic effects of new benzimidazole derivatives bearing hydrazone moiety. J Heterocyclic Chemistry. 2017; 55:138. https://doi:10.1002/jhet.3016.
- Singh H, Lonare MK, Sharma M, Udehiya R, Singla S, Saini SP, Dumka VK. Interactive effect of carbendazim and imidacloprid on buffalo bone marrow derived mesenchymal stem cells: Oxidative stress, cytotoxicity and genotoxicity. Drug Chem Toxicol. 2021; 29:1-15. https://doi.org/10.1080/01480545.2021.2007023. PMID: 34844488.
- Caron-Beaudoin E, Viau R, Hudon-Thibeault AA, Vaillancourt C, Sanderson JT. The use of a unique co-culture model of fetoplacental steroidogenesis as a screening tool for endocrine disruptors: The effects of neonicotinoids on aromatase activity and hormone production. Toxicol Appl Pharmacol. 2017; 332:15-24. https://doi.org/10.1016/j.taap.2017.07.018. PMID: 28750898.
- Lonare M, Kumar M, Raut S, Badgujar P, Doltade S, Telang A. Evaluation of imidacloprid-induced neurotoxicity in male rats: A protective effect of curcumin. Neurochem Int. 2014; 78:122-129. https://doi.org/10.1016/j.neuint.2014.09.004. PMID: 25261201.
- Chakroun, Intissar G, Lobna E, Oumaïma A, Fadoua N, Emna K, Najjar MF, Zohra H, Hassen BC. Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological Assessment. J Coastal Life Med. 2017; 5(12):540-546. https://doi.org/10.12980/jclm.5.2017J7-149.
- Casida JE. Pesticide interactions: Mechanisms, benefits, and risks. J Agric Food Chem. 2017; 65(23):4553-4561. https://doi:10.1021/acs.jafc.7b01813.
- Hernández AF, Gil F, Lacasaña M. Toxicological interactions of pesticide mixtures: An update. Arch Toxicol. 2017; 91(10):3211-3223. https://doi.org/10.1007/s00204-017-2043-5. PMID: 28845507.
- Lonare MK, Vemu B, Singh AK, Dumka VK, Singla S, Sharma SK. Cytotoxicity and oxidative stress alterations induced by aldrin in BALB/c 3T3 fibroblast cells. Proc Natl Acad Sci India Sect B Biol Sci. 2017; 87:1209-1216. https://doi.org/10.1007/s40011-015-0694-7.
- Gade NE, Pratheesh MD, Nath A, Dubey PK, Amarpal, Sharma B, Saikumar G, Taru Sharma G. Molecular and cellular characterization of buffalo bone marrow-derived mesenchymal stem cells. Reprod Domest Anim. 2013; 48(3):358-367. https://doi.org/10.1111/j.1439-0531.2012.02156.x.
- Devi P, Sharma M, Singh SD, Lonare MK, Udehiya R. Viability and expression pattern of cryopreserved mesenchymal stem cells derived from buffalo bone marrow. Ruminant Sci. 2017; 6(1):7-12.
- Aranda A, Sequedo L, Tolosa L, Quintas G, Burello E, Castell JV, Gombau L. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. Toxicol In Vitro. 2013; 27(2):954-963. https://doi.org/10.1016/j.tiv.2013.01.016. PMID: 23357416.
- Salmon ED, Shaw SL, Waters JC, Waterman-Storer CM, Maddox PS, Yeh E, Bloom K. A high-resolution multimode digital microscope system. Methods Cell Biol. 2007; 81:187-218. https://doi.org/10.1016/S0091-679X(06)81011-3. PMID: 17519169.
- Doan CC, Truong NH, Vu NB, Nguyen TT, Nguyen HM, Nguyen KG, Do S, Phan NK, Pham PV. Isolation, culture and cryopreservation of human bone marrow derived mesenchymal stem cells. Int J Plant Animal Env Sci. 2012; 2(2):358-367.
- Yu Y, Yao AH, Chen N, Pu LY, Fan Y, Lv L, Sun BC, Li GQ, Wang XH. Mesenchymal stem cells over-expressing hepatocyte growth factor improve small-for-size liver grafts regeneration. Mol Ther. 2007; 15(7):1382-1389. https://doi.org/10.1038/sj.mt.6300202. PMID: 17519892.
- de Macedo Braga LM, Lacchini S, Schaan BD, Rodrigues B, Rosa K, De Angelis K, Borges LF, Irigoyen MC, Nardi NB. In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction. J Biomed Sci. 2008; 15(3):365-374. https://doi.org/10.1007/s11373-008-9237-z. PMID: 18256904.
- Peterbauer-Scherb A, van Griensven M, Meinl A, Gabriel C, Redl H, Wolbank S. Isolation of pig bone marrow mesenchymal stem cells suitable for one-step procedures in chondrogenic regeneration. J Tissue Eng Regen Med. 2010; 4(6):485-490. https://doi.org/10.1002/term.262. PMID: 20112279.
- McCarty RC, Gronthos S, Zannettino AC, Foster BK, Xian CJ. Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells. J Cell Physiol. 2009; 219(2):324-333. https://doi.org/10.1002/jcp.21670. PMID: 19115243.
- Rentsch C, Hess R, Rentsch B, Hofmann A, Manthey S, Scharnweber D, Biewener A, Zwipp H. Ovine bone marrow mesenchymal stem cells: isolation and characterization of the cells and their osteogenic differentiation potential on embroidered and surface-modified polycaprolactone-co-lactide scaffolds. In Vitro Cell Dev Biol Anim. 2010; 46(7):624-634. https://doi.org/10.1007/s11626-010-9316-0. PMID: 20490706.
- Honda H, Tomizawa M, Casida JE. Neo-nicotinoid metabolic activation and inactivation established with coupled nicotinic receptor-CYP3A4 and -aldehyde oxidase systems. Toxicol Lett. 2006; 161(2):108-114. https://doi.org/10.1016/j.toxlet.2005.08.004. PMID: 16153789.
- Tomizawa M, Lee DL, Casida JE. Neonicotinoid insecticides: molecular features conferring selectivity for insect versus mammalian nicotinic receptors. J Agric Food Chem. 2000; 48(12):6016-6024. https://doi.org/10.1021/jf000873c. PMID: 11312774.
- Abolaji AO, Awogbindin IO, Adedara IA, Farombi EO. Insecticide chlorpyrifos and fungicide carbendazim, common food contaminants mixture, induce hepatic, renal, and splenic oxidative damage in female rats. Hum Exp Toxicol. 2017; 36(5):483-493. https://doi.org/10.1177/0960327116652459. PMID: 27268782.
- Chauhan LK, Varshney M, Pandey V, Sharma P, Verma VK, Kumar P, Goel SK. ROS-dependent genotoxicity, cell cycle perturbations and apoptosis in mouse bone marrow cells exposed to formulated mixture of cypermethrin and chlorpyrifos. Mutagenesis. 2016; 31(6):635-642. https://doi.org/10.1093/mutage/gew031. PMID: 27470700.
- Abhishek A, Ansari NG, Shankhwar SN, Jain A, Singh V. In vitro toxicity evaluation of low doses of pesticides in individual and mixed condition on human keratinocyte cell line. Bioinformation. 2014; 31;10(12):716-720. https://doi.org/10.6026/97320630010716. PMID: 25670872.
- Sands M, Kron MA, Brown RB. Pentamidine: a review. Rev Infect Dis. 1985; 7(5):625-634. https://doi.org/10.1093/clinids/ 7.5.625. PMID: 3903942.
- Vercesi AE, Docampo R. Ca2+ transport by digitonin-permeabilized Leishmania donovani. Effects of Ca2+, pentamidine and WR-6026 on mitochondrial membrane potential in situ. Biochem J. 1992; 284 (Pt 2)(Pt 2):463-467. https://doi.org/10.1042/bj2840463. PMID: 1376113.
- Andréo R, Regasini LO, Petrônio MS, Chiari-Andréo BG, Tansini A, Silva DH, Cicarelli RM. Toxicity and Loss of Mitochondrial Membrane Potential Induced by Alkyl Gallates in Trypanosoma cruzi. Int Sch Res Notices. 2015; 2015:924670. https://doi:10.1155/2015/924670. PMID: 27347554.
- Sakamuru S, Attene-Ramos MS, Xia M. Mitochondrial Membrane Potential Assay. Methods Mol Biol. 2016; 1473:17-22. https://doi.org/10.1007/978-1-4939-6346-1_2. PMID: 27518619.
- Area-Gomez E, Del Carmen Lara Castillo M, Tambini MD, Guardia-Laguarta C, de Groof AJ, Madra M, Ikenouchi J, Umeda M, Bird TD, Sturley SL, Schon EA. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 2012; 5; 31(21):4106-4123. https://doi.org/10.1038/emboj.2012.202. PMID: 22892566.
- Adachi M, Ishii H. Role of mitochondria in alcoholic liver injury. Free Radic Biol Med. 2002; 32(6):487-491. https://doi.org/10.1016/s0891-5849(02)00740-2. PMID: 11958949.
- Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013; 75:685-705. https://doi.org/10.1146/annurev-physiol-030212-183653. PMID: 23140366.
- Shahini A, Choudhury D, Asmani M, Zhao R, Lei P, Andreadis ST. NANOG restores the impaired myogenic differentiation potential of skeletal myoblasts after multiple population doublings. Stem Cell Res. 2018; 26:55-66. https://doi.org/10.1016/j.scr.2017.11.018. PMID: 29245050.
- Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature. 2016; 530(7589):184-189. https://doi.org/10.1038/nature16932. PMID: 26840489.
- Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K. Cancer and Aging as Consequences of Un-Repaired DNA Damage. New Research on DNA Damages. New York, USA: Nova Science Publishers; 2008. p.1-47.
- Pan MR, Li K, Lin SY, Hung WC. Connecting the dots: From DNA damage and repair to Aging. Int J Mol Sci. 2016; 17(5):685. https://doi.org/10.3390/ijms17050685. PMID: 27164092.
- Menon R, Boldogh I, Urrabaz-Garza R, Polettini J, Syed TA, Saade GR, Papaconstantinou J, Taylor RN. Senescence of primary amniotic cells via oxidative DNA damage. PLoS One. 2013; 8(12):e83416. https://doi.org/10.1371/journal.pone.0083416. PMID: 24386195.
Abstract Views: 188
PDF Views: 0