Abstract
Abamectin is a commonly used pesticide in agriculture and fisheries and poses a risk to aquatic species. However, the mechanism of its toxic effects on fish remains to be discovered. In this study, we explored the effects of abamectin exposure at different concentrations on the respiratory system of carp. Carp were divided into three groups, namely the control group, low-dose abamectin treatment group, and high-dose abamectin treatment group. Gill tissue was collected after abamectin exposure for histopathological, biochemical, tunnel, mRNA, and protein expression analysis. Histopathological analysis indicated that abamectin damaged the gill structure. Biochemical analysis showed that abamectin triggered oxidative stress with lowered antioxidant enzyme activities and increased MDA content. Moreover, abamectin led to enhanced INOS levels and pro-inflammatory transcription, activating inflammation. Tunnel results demonstrated that exposure to abamectin induced gill cell apoptosis through an exogenous pathway. In addition, exposure to abamectin activated the PI3K/AKT/mTOR pathway, leading to inhibition of autophagy. Overall, abamectin caused respiratory system toxicity in carp via triggering oxidative stress, inflammation, and apoptosis and inhibiting autophagy. The study suggests that abamectin has a profound toxicity mechanism in the respiratory system of carp, contributing to a better understanding of pesticide risk assessment in aquatic systems.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
All data generated or analyzed during this study are available from the corresponding author on reasonable request.
References
Ahmad H, Yousafzai AM, Siraj M, Ahmad R, Ahmad I, Nadeem MS, Ahmad W, Akbar N, Muhammad K (2015) Pollution problem in River Kabul: accumulation estimates of heavy metals in native fish species. Biomed Res Int 2015:537368. https://doi.org/10.1155/2015/537368
Bai SH, Ogbourne S (2016) Eco-toxicological effects of the avermectin family with a focus on abamectin and ivermectin. Chemosphere 154:204–214. https://doi.org/10.1016/j.chemosphere.2016.03.113
Cappello T, Brandão F, Guilherme S, Santos MA, Maisano M, Mauceri A, Canário J, Pacheco M, Pereira P (2016) Insights into the mechanisms underlying mercury-induced oxidative stress in gills of wild fish (Liza aurata) combining (1)H NMR metabolomics and conventional biochemical assays. Sci Total Environ 548–549:13–24. https://doi.org/10.1016/j.scitotenv.2016.01.008
Chen LJ, Sun BH, Qu JP, Xu S, Li S (2013) Avermectin induced inflammation damage in king pigeon brain. Chemosphere 93:2528–2534. https://doi.org/10.1016/j.chemosphere.2013.09.058
Chen J, Liu M, Zhang L (2016) Avermectin, from winning the Nobel Prize to “innovation in China.” Wei Sheng Wu Xue Bao 56:543–558
Chen K, Zhou X-Q, Jiang W-D, Wu P, Liu Y, Jiang J, Kuang S-Y, Tang L, Tang W-N, Feng L (2019) Dietary phosphorus deficiency caused alteration of gill immune and physical barrier function in the grass carp (Ctenopharyngodon idella) after infection with Flavobacterium columnare. Aquaculture 506:1–13. https://doi.org/10.1016/j.aquaculture.2019.03.018
Chen J, Liu N, Li B, Zhang H, Zhao Y, Cao X (2021) The effects of fipronil exposure on oxidative stress, non-specific immunity, autophagy, and apoptosis in the common carp. Environ Sci Pollut Res Int 28:27799–27810. https://doi.org/10.1007/s11356-021-12573-x
Crump A, Ōmura S (2011) Ivermectin, “wonder drug” from Japan: the human use perspective. Proc Jpn Acad Ser B Phys Biol Sci 87:13–28. https://doi.org/10.2183/pjab.87.13
De Domenico E, Mauceri A, Giordano D, Maisano M, Giannetto A, Parrino V, Natalotto A, D’Agata A, Cappello T, Fasulo S (2013) Biological responses of juvenile European sea bass (Dicentrarchus labrax) exposed to contaminated sediments. Ecotoxicol Environ Saf 97:114–123. https://doi.org/10.1016/j.ecoenv.2013.07.015
de Faria DBG, Montalvão MF, de Souza JM, de Oliveira MB, Malafaia G, Rodrigues ASL (2018) Analysis of various effects of abamectin on erythrocyte morphology in Japanese quails (Coturnix japonica). Environ Sci Pollut Res Int 25:2450–2456. https://doi.org/10.1007/s11356-017-0677-8
Diao L, Tang N, Zhang C, Cheng J, Zhang Z, Wang S, Wu C, Zhang L, Tao L, Li Z, Zhang Y (2021) Avermectin induced DNA damage to the apoptosis and autophagy in human lung epithelial A549 cells. Ecotoxicol Environ Saf 215:112129. https://doi.org/10.1016/j.ecoenv.2021.112129
Du C, Zhang T, Xiao X, Shi Y, Duan H, Ren Y (2017) Protease-activated receptor-2 promotes kidney tubular epithelial inflammation by inhibiting autophagy via the PI3K/Akt/mTOR signalling pathway. Biochem J 474:2733–2747. https://doi.org/10.1042/bcj20170272
Duzguner V, Erdogan S (2012) Chronic exposure to imidacloprid induces inflammation and oxidative stress in the liver & central nervous system of rats. Pestic Biochem Physiol 104:58–64. https://doi.org/10.1016/j.pestbp.2012.06.011
El-Shenawy NS (2010) Effects of insecticides fenitrothion, endosulfan and abamectin on antioxidant parameters of isolated rat hepatocytes. Toxicol in Vitro 24:1148–1157. https://doi.org/10.1016/j.tiv.2010.03.001
Evans DH, Piermarini PM, Choe KP (2005) The multifunctional fish gill: dominant site of gas exchange, osmoregulation, acid-base regulation, and excretion of nitrogenous waste. Physiol Rev 85:97–177. https://doi.org/10.1152/physrev.00050.2003
Fei D, Zhao H, Wang Y, Liu J, Mu M, Guo M, Yang X, Xing M (2019) The disturbance of autophagy and apoptosis in the gizzard caused by copper and/or arsenic are related to mitochondrial kinetics. Chemosphere 231:1–9. https://doi.org/10.1016/j.chemosphere.2019.05.101
Hong Y, Huang Y, Huang Z (2020) Oxidative stress, immunological response, and heat shock proteins induction in the Chinese mitten crab, Eriocheir sinensis following avermectin exposure. Environ Toxicol 35:213–222. https://doi.org/10.1002/tox.22858
Horsberg TE (2012) Avermectin use in aquaculture. Curr Pharm Biotechnol 13:1095–1102. https://doi.org/10.2174/138920112800399158
Ignacio Barrasa J, Olmo N, Pérez-Ramos P, Santiago-Gómez A, Lecona E, Turnay J, Antonia Lizarbe M (2011) Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells. Apoptosis 16:1054–1067. https://doi.org/10.1007/s10495-011-0633-x
Jiao W, Han Q, Xu Y, Jiang H, Xing H, Teng X (2019) Impaired immune function and structural integrity in the gills of common carp (Cyprinus carpio L.) caused by chlorpyrifos exposure: through oxidative stress and apoptosis. Fish Shellfish Immunol 86:239–245. https://doi.org/10.1016/j.fsi.2018.08.060
Kaminskyy VO, Zhivotovsky B (2014) Free radicals in cross talk between autophagy and apoptosis. Antioxid Redox Signal 21:86–102. https://doi.org/10.1089/ars.2013.5746
khalil M (2013) Abamectin and azadirachtin as eco-friendly and promising biorational tools in integrated nematodes management programs. J Plant Pathol Microbiol 4. https://doi.org/10.4172/2157-7471.1000174
Kimura H, Kamiyama K, Imamoto T, Takeda I, Masunaga S, Kobayashi M, Mikami D, Takahashi N, Kasuno K, Sugaya T, Iwano M (2022) Fenofibrate reduces cisplatin-induced apoptosis by inhibiting the p53/Puma/caspase-9 pathway and the MAPK/caspase-8 pathway rather than by promoting autophagy in murine renal proximal tubular cells. Biochem Biophys Rep 30:101237. https://doi.org/10.1016/j.bbrep.2022.101237
Lasota JA, Dybas RA (1991) Avermectins, a novel class of compounds: implications for use in arthropod pest control. Annu Rev Entomol 36:91–117. https://doi.org/10.1146/annurev.en.36.010191.000515
Leuti A, Fazio D, Fava M, Piccoli A, Oddi S, Maccarrone M (2020) Bioactive lipids, inflammation and chronic diseases. Adv Drug Deliv Rev 159:133–169. https://doi.org/10.1016/j.addr.2020.06.028
Li MY, Gao CS, Du XY, Zhao L, Niu XT, Wang GQ, Zhang DM (2020) Effect of sub-chronic exposure to selenium and astaxanthin on Channa argus: bioaccumulation, oxidative stress and inflammatory response. Chemosphere 244:125546. https://doi.org/10.1016/j.chemosphere.2019.125546
Li M, Zhang P, Xu W, Yuan J, Li Q, Tao L, Li Z, Zhang Y (2021) Avermectin induces toxic effects in insect nontarget cells involves DNA damage and its associated programmed cell death. Comp Biochem Physiol C Toxicol Pharmacol 249:109130. https://doi.org/10.1016/j.cbpc.2021.109130
Liang Y, Li J, Lin Q, Huang P, Zhang L, Wu W, Ma Y (2017) Research progress on signaling pathway-associated oxidative stress in endothelial cells. Oxid Med Cell Longev 2017:7156941. https://doi.org/10.1155/2017/7156941
Liu C, Zhao Y, Chen L, Zhang Z, Li M, Li S (2015) Avermectin induced autophagy in pigeon spleen tissues. Chem Biol Interact 242:327–333. https://doi.org/10.1016/j.cbi.2015.10.022
Lumaret JP, Errouissi F (2002) Use of anthelmintics in herbivores and evaluation of risks for the non target fauna of pastures. Vet Res 33:547–562. https://doi.org/10.1051/vetres:2002038
Ma Y, Liu H, Xia X, Ning M, Ji B, Li Y, Li H, Du J, Sun W, Gu W, Meng Q (2021) Toxicity of avermectin to Eriocheir sinensis and the isolation of a avermectin-degrading bacterium, Ochrobactrum sp. AVM-2. Ecotoxicol Environ Saf 230:113115. https://doi.org/10.1016/j.ecoenv.2021.113115
Matés JM, Segura JA, Alonso FJ, Márquez J (2012) Oxidative stress in apoptosis and cancer: an update. Arch Toxicol 86:1649–1665. https://doi.org/10.1007/s00204-012-0906-3
Mohammed AJ, Abdul-Kareem S, Ajaweed AN, Hameed AM, Mahdii BA (2018) Histological changes resulting from the use of sublethal concentrations from insecticide abamectin in the common carp (Cyprinus carpio L. 1758). Eco Env and Cons 24:565–571
Ni H, Peng L, Gao X, Ji H, Ma J, Li Y, Jiang S (2019) Effects of maduramicin on adult zebrafish (Danio rerio): acute toxicity, tissue damage and oxidative stress. Ecotoxicol Environ Saf 168:249–259. https://doi.org/10.1016/j.ecoenv.2018.10.040
Novelli A, Vieira BH, Braun AS, Mendes LB, Daam MA, Espíndola EL (2016) Impact of runoff water from an experimental agricultural field applied with Vertimec® 18EC (abamectin) on the survival, growth and gill morphology of zebrafish juveniles. Chemosphere 144:1408–1414. https://doi.org/10.1016/j.chemosphere.2015.10.004
Nunes B, Antunes SC, Gomes R, Campos JC, Braga MR, Ramos AS, Correia AT (2015) Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations. Arch Environ Contam Toxicol 68:371–381. https://doi.org/10.1007/s00244-014-0101-z
Pan YX, Luo Z, Zhuo MQ, Wei CC, Chen GH, Song YF (2018) Oxidative stress and mitochondrial dysfunction mediated Cd-induced hepatic lipid accumulation in zebrafish Danio rerio. Aquat Toxicol 199:12–20. https://doi.org/10.1016/j.aquatox.2018.03.017
Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990. https://doi.org/10.1016/j.cellsig.2012.01.008
Shaw P, Mondal P, Bandyopadhyay A, Chattopadhyay A (2020) Environmentally relevant concentration of chromium induces nuclear deformities in erythrocytes and alters the expression of stress-responsive and apoptotic genes in brain of adult zebrafish. Sci Total Environ 703:135622. https://doi.org/10.1016/j.scitotenv.2019.135622
Tang KK, Liu XY, Wang ZY, Qu KC, Fan RF (2019) Trehalose alleviates cadmium-induced brain damage by ameliorating oxidative stress, autophagy inhibition, and apoptosis. Metallomics 11:2043–2051. https://doi.org/10.1039/c9mt00227h
van Den Heuvel WJA, Halley BA, Ku CC, Jacob TA, Wislocki PG, Forbis AD (1996) Bioconcentration and depuration of avermectin B 1a in the bluegill sunfish. Environ Toxicol Chem 15:2263–2266
Wang LL, Liu T, Wang C, Zhao FQ, Zhang ZW, Yao HD, Xing HJ, Xu SW (2013) Effects of atrazine and chlorpyrifos on the production of nitric oxide and expression of inducible nitric oxide synthase in the brain of common carp (Cyprinus carpio L.). Ecotoxicol Environ Saf 93:7–12. https://doi.org/10.1016/j.ecoenv.2013.03.007
Wang LY, Fan RF, Yang DB, Zhang D, Wang L (2019) Puerarin reverses cadmium-induced lysosomal dysfunction in primary rat proximal tubular cells via inhibiting Nrf2 pathway. Biochem Pharmacol 162:132–141. https://doi.org/10.1016/j.bcp.2018.10.016
Yeşilbudak B, Erdem C (2014) Cadmium accumulation in gill, liver, kidney and muscle tissues of common carp, Cyprinus carpio, and Nile tilapia, Oreochromis niloticus. Bull Environ Contam Toxicol 92:546–550. https://doi.org/10.1007/s00128-014-1228-3
Zhang T, Dong Z, Liu F, Pan E, He N, Ma F, Wang G, Wang Y, Dong J (2022a) Avermectin induces carp neurotoxicity by mediating blood-brain barrier dysfunction, oxidative stress, inflammation, and apoptosis through PI3K/Akt and NF-κB pathways. Ecotoxicol Environ Saf 243:113961. https://doi.org/10.1016/j.ecoenv.2022.113961
Zhang T, Dong Z, Liu F, Pan E, He N, Ma F, Wu X, Wang Y, Dong J (2022b) Non-target toxic effects of avermectin on carp spleen involve oxidative stress, inflammation, and apoptosis. Pestic Biochem Physiol 187:105190. https://doi.org/10.1016/j.pestbp.2022.105190
Zhao H, Wang Y, Shao Y, Liu J, Wang S, Xing M (2018) Oxidative stress-induced skeletal muscle injury involves in NF-κB/p53-activated immunosuppression and apoptosis response in copper (II) or/and arsenite-exposed chicken. Chemosphere 210:76–84. https://doi.org/10.1016/j.chemosphere.2018.06.165
Zhao H, Wang Y, Guo M, Liu Y, Yu H, Xing M (2021) Environmentally relevant concentration of cypermethrin or/and sulfamethoxazole induce neurotoxicity of grass carp: involvement of blood-brain barrier, oxidative stress and apoptosis. Sci Total Environ 762:143054. https://doi.org/10.1016/j.scitotenv.2020.143054
Zhao P, Wang Y, Yang Q, Yu G, Ma F, Dong J (2022) Abamectin causes cardiac dysfunction in carp via inhibiting redox equilibrium and resulting in immune inflammatory response and programmed cell death. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-022-24004-6
Zhu WJ, Li M, Liu C, Qu JP, Min YH, Xu SW, Li S (2013) Avermectin induced liver injury in pigeon: mechanisms of apoptosis and oxidative stress. Ecotoxicol Environ Saf 98:74–81. https://doi.org/10.1016/j.ecoenv.2013.09.021
Zhu S, Zhou J, Zhou Z, Zhu Q (2019) Abamectin induces apoptosis and autophagy by inhibiting reactive oxygen species-mediated PI3K/AKT signaling in MGC803 cells. J Biochem Mol Toxicol 33:e22336. https://doi.org/10.1002/jbt.22336
Acknowledgements
The work was supported by the Basic Science (Natural Science) Research Project of Higher Education of Jiangsu Province (no. 21KJB230001), the Open-end Funds of Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening (no. HY202101), and the Priority Academic Program Development of Jiangsu Higher Education Institutions of China. The authors thank these funders for their financial support. The funders had no role in the study design, data collection and analysis, publication decision, or manuscript preparation.
Author information
Authors and Affiliations
Contributions
Huimiao Feng: investigation, methodology, writing—original draft. Ping Zhou: investigation, methodology, writing—original draft. Feixue Liu: data curation, formal analysis. Wei Zhang: methodology, data curation, investigation. Haitao Yang: methodology, data curation, investigation. Xueqing Li: methodology, data curation, investigation. Jingquan Dong: conceptualization, funding acquisition, project administration, supervision. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Consent for publication
Not applicable.
Consent to participate
Not applicable.
Competing interests
The authors declare no competing interests.
Additional information
Responsible Editor: Bruno Nunes
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Feng, H., Zhou, P., Liu, F. et al. Abamectin causes toxicity to the carp respiratory system by triggering oxidative stress, inflammation, and apoptosis and inhibiting autophagy. Environ Sci Pollut Res 30, 55200–55213 (2023). https://doi.org/10.1007/s11356-023-26166-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-023-26166-3