The Effect of Acetamiprid Administration on Bcl-2 Immunoreactivity in the Liver




Bcl-2, immunoreactivity, acetamiprid, liver, albinos mice


This study aimed to show the effect of acetamiprid, a neonicotinoid insecticide, on B-cell lymphoma 2 (Bcl-2) gene expression, which plays an important role in apoptotic mechanisms in liver tissue. The study consisted of four groups in total, in which three doses of acetamiprid (5, 10, and 15 mg kg-1) were administered, together with the negative group, in which no substance was administered. Liver tissues resected from mice sacrificed by cervical dislocation after 14 days of acetamiprid administration by gavage were fixed in a 10% formaldehyde solution for histological and immunohistochemical analyses and blocked in paraffin after routine tissue follow-up, and sections were stained with haematoxylin-eosin and immunostaining. Histological analysis revealed normal liver tissue in the control group; whereas, sinusoidal dilatation, vasodilatation, and necrosis and steatosis in the parenchyma were found in the acetamiprid-treated group at an increasing rate depending on the dose amount. The immunoreactivity of Bcl-2 in liver tissue was observed in the sinusoidal epithelium. Bcl-2 immunoreactivity was observed severely in the control and 5 mg kg-1 groups and moderately in the 10 mg kg-1 and 15 mg kg-1 acetamiprid-treated groups. Bcl-2 immunoreactivity was observed homogenously in the region from the central vein to the Kiernan’s space. It was observed that acetamiprid used in the study showed a toxic effect on liver tissue, affected bcl-2 expression, an important biomarker in apoptotic pathways, and induced a dose-dependent decrease in bcl-2 immunoreactivity.


Arfat, Y., Mahmood, N., Tahir, M. U., Rashid, M., Anjum, S., Zhao, F., Li, D., Sun, Y., Hu, L., Zhihao, C., Yin, C., Shang, P., & Qian, A. (2014). Effect of imidacloprid on hepatotoxicity and nephrotoxicity in male albino mice. Toxicology Report, 1, 554-561.

Badgujar, P. C., Jain, S., Singh, A., Punia, J., Gupta, R., & Chandra-tre, G. A. (2013). Immunotoxic effects of imidacloprid following 28 days of oralexposure in BALB/c mice. Environ Toxicol Pharmacol, 35(3), 408-418.

Bhardwaj, S., Srivastava, M. K., Kapoor, U., & Srivastava, L. P. (2010). A 90 days oral toxicity of imidacloprid in female rats: morphological, biochemical and histopathological evaluations. Food and Chemical Toxicology, 48(5), 1185-1190.

Bonmatin, J. M., Giorio, C., Girolami, V., Goulson, D., Kreutzweiser, D. P., Krupke, C., Liess, M., Long, E., Marzaro, M., Mitchell, E. A. D., Noome, D. A., Simon-Delso, N., & Tapparo, A. (2015). Environmental fate and exposure; neonicotinoids and fipronil. Environmental Science and Pollution Research, 22(1), 35-67.

Bonmatin, J. M., Mitchell, E. A. D., Glauser, G., Lumawig-Heitzman, E., Claveria, F., Bijleveld van Lexmond, M., Taira, K., & Sánchez-Bayo, F. (2021). Residues of neonicotinoids in soil, water and people's hair: A case study from three agricultural regions of the Philippines. Science of The Total Environment, 757, 143822.

Camp, A. A., Batres, M. A., Williams, W. C., Koethe, R. W., Stoner, K. A., & Lehmann, D. M. (2020). Effects of the Neonicotinoid Acetamiprid in Pollen on Bombus impatiens Microcolony Development. Environ Toxicol Chem, 39(12), 2560-9.

Chakroun, S., Ezzi, L., Grissa, I., Kerkeni, E., Neffati, F., Bhouri, R., Sallem, A., Najjar, M. F., Hassine, M., Mehdi, M., Haouas, Z., & Cheikhe, H. B. (2016). Hematological, biochemical, and toxicopathic effects of subchronic acetamiprid toxicity in Wistar rats. Environmental Science and Pollution Research, 23, 25191-25199.

Chalazonitis, A., Gershon, M., & Greene, L. (2012). Cell death and the developing enteric nervous system. Neurochemistry International, 61(6): 839-47.

Çil, G. İ., Korkmaz, S. D., Ozansoy, G., & Küplülü, Ö. (2020). Türkiye’deki Bal Örneklerinde Neonikotinoid Varlığının LC-MS/Q-TOF Yöntemi ile Tespiti. MAKU J. Health Sci. Inst, 8(1), 11-17.

Craddock, H. A., Huang, D., Turner, P. C., Quirós-Alcalá, L., & Payne-Sturges, D. C. (2019). Trends in neonicotinoid pesticide residues in food and water in the United States, 1999-2015. Environmental Health, 18(7), 1-16.

Deveci, H. A., Nur, G., & Aksu Kılıçle, P. (2021). Subakut malathion uygulamasının oksidatif stres biyobelirteçlerine etkisi. Journal of Advances in VetBio Science and Techniques, 6(3), 193-201.

Dogan, D., Nur, G., & Deveci, H. A. (2022). Tissue-specific toxicity of clothianidin on rainbow trout (Oncorhynchus mykiss). Drug and Chemical Toxicology, 45(4), 1851-1861.

El-Din, M. A. E. S., Ghareeb A. E. E., El-Garawani, I. M., & El-Rahman, H. A. A. (2023). Induction of apoptosis, oxidative stress, hormonal, and histological alterations in the reproductive system of thiamethoxam-exposed female rats. Environmental Science and Pollution Research, 30(31), 77917-77930.

El-Garawani, I. M., Khallaf, E. A., Alnenaei, A. A., Elgendy, R. G., Sobhy, H. M., Khairallah, A., Hathout., H. M. R., Malhat, F., & Nofal, A. E. (2022). The Effect of Neonicotinoids Exposure on Oreochromis niloticus Histopathological Alterations and Genotoxicity. Bulletin of Environmental Contamination and Toxicology, 109, 1001-1009.

Evan, A. P., Lingeman, J., Coe, F., Shao, Y., Miller, N., Matlaga, B., Phillips, C., Sommer, A., & Worcester, E. (2007). Renal histopathology of stone-forming patients with distal renal tubular acidosis. Kidney International, 71, 795-801.

Gaweł, M., Kiljanek, T., Niewiadowska, A., Semeniuk, S., Goliszek, M., Burek, O., & Posyniak, A. (2019). Determination of neonicotinoids and 199 other pesticide residues in honey by liquid and gas chromatography coupled with tandem mass spectrometry. Food Chemistry, 282, 36-47.

Gelen, V., Şengül, E., Gedikli, S., Atila, G., Uslu, H., & Makav, M. (2017). The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pacific Journal of Tropical Biomedicine, 7(7), 647-653.

Gupta, R. K., Gupta, S., Gajbhiye, V. T., Wiener, H., & Singhet, G. (2005). Residues of imidacloprid, acetamiprid and thiamethoxam in gram. Pesticide Research Journal, 17(1), 46-50

Gür, C., Özkanlar, S., Gedikli, S., Şengül, E., Gelen, V., & Kara, A. (2022). The Effects of Quercetin Administration on Heart Tissue and Serum Parameters in the Rats with Experimental Obesity. Eurasian Journal of Molecular and Biochemical Sciences, 1(1), 16-21.

Karaca, B. U., Arican, Y. E., Boran, T., Binay, S., Okyar, A., Kaptan, E., & Özhan, G. (2019). Toxic effects of subchronic oral acetamiprid exposure in rats. Toxicology and Industrial Health, 35(11-12), 679-687.

Kammon, A. M., Brar, R. S., Banga, H. S., & Sodhi, S. (2010). Patho-biochemical studies on hepatotoxicity and nephrotoxicity on exposure to chlorpyrifos and imidacloprid in layer chickens. Veterinarski Arhiv 80, 663-672.

Kapoor, U., Srivastava, M. K., Trivedi, P., Garg, V., & Srivastava, L. P. (2014). Disposition and acute toxicity of imidacloprid in female rats after single exposure. Food and Chemical Toxicology, 68, 190-195.

Khaldoun, H., Bouzid, N., Boukreta, S., Makhlouf, C., & Derriche, F. (2017). Thiamethoxam Actara® induced alterations in kidney liver cerebellum and hippocampus of male rats. Journal of Xenobiotics, 7(7149), 25-30.

Khovarnagh, N., & Seyedalipour, B. (2021). Antioxidant, histopathological and biochemical outcomes of short-term exposure to acetamiprid in liver and brain of rat: The protective role of N-acetylcysteine and S-methylcysteine. Saudi Pharmaceutical Journal, 29(3): 280-289.

Kumar, A., Tomar, M., & Kataria, S. K. (2014). Effect of sub-lethal doses of imidacloprid on histological and biochemical parameters in female albino mice. IOSR Journal of Environmental Science, Toxicology and Food Technology, 8(1), ver: IV: 09-15.

Marrs, T. C. (2012). Toxicology of Insecticides-Introductory Considerations. In T. Marrs (Eds.), Mammalian Toxicology of Insecticides (pp. 1-13). Chapter I, Royal Society of Chemistry.

Matsuda, K., Buckingham, S. D., Kleier, D., Rauh, J. J., Grauso, M., & Sattelle, D. B. (2001). Neonicotinoids: insecticides acting on insect nicotinic acetylcholine receptors. Trends in Pharmacological Sciences, 22(11), 573-80.

Naraharisetti, S. B., Aggarwal, M., Ranganathan, V., Sarkar, S. N., Kataria, M., & Malik, J. K. (2009). Effects of simultaneous repeated exposure at high levels of arsenic and malathion on hepatic drug biotransforming enzymes in broiler chickens. Environmental Toxicology and Pharmacology, 28(2), 213-218.

Nur, G., Caylak, E., Kilicle, P. A., Sandayuk, S., & Celebi, O. O. (2022). Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity. Open Medicine (Wars), 17(1), 1788-1796.

Nur, G., Deveci, H. A., & Koc, E. (2021). Preservation of Vitamin-E Against Nephrotoxic Effect Induced by Subacute Dichlorvos Application. Fresenius Environmental Bulletin, 30(7), 8651-8659

Nur, G., Akar, F., & Akar, F. (2023a). The Effects of Neonicotinoid Insecticide/Thiamethoxamin on Environmental and Aquatic Ecosystems. International Journal of Advanced Natural Sciences and Engineering Researches, 7(10), 466-472.

Nur, G., Caylak, E., Deveci, H. A., Kılıcle, P. A, & Deveci, A. (2023b). The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin. Open Medicine, 18(1): 20230781.

Önen, Ö., Kılıçle, P. A., Adalı, Y., & Beşeren, H. (2018). The Histopathological and Genotoxic Effects of Neonicotinoid Pesticides. Bozok Medical Journal, 8(1), 139-147.

Phogat, A., Singh, J., Kumar, V., & Malik, V. (2023). Berberine mitigates acetamiprid-induced hepatotoxicity and inflammation via regulating endogenous antioxidants and NF-κB/TNF-α signaling in rats. Environmental Science and Pollution Research, 30(37), 87412-87423.

Ploumaki, I., Triantafyllou, E., Koumprentziotis, I. A., Karampinos, K., Drougkas, K., Karavolias, I., Trontzas, I., & Kotteas, E. A. (2023). Bcl-2 pathway inhibition in solid tumors: a review of clinical trials. Clinical and Translational Oncology, 25(6), 1554-1578.

Pramanik, S. K., Bhattacharyya, J., Dutta, S., Dey, P. K., & Bhattacharyya, A. (2006). Persistence of Acetamiprid in/on Mustard (Brassica juncea L.). Bulletin of Environmental Contamination and Toxicology, 76(2), 356-60.

Qian, S., Wei, Z., Yang, W., Huang, J., Yang, Y., & Wang, J. (2022). The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Frontiers in Oncology, 12, 985363.

Rasgele, P. G., Oktay, M., Kekecoglu, M., Muranli, F. D. G. (2015). The histopathological investigation of liver in experimental animals after shortterm exposures to pesticides. Bulgarian Journal of Agricultural Science, 21(2), 446-453.

Seidal, T., Balaton, A. J., & Battifora, H. (2001). Interpretation and quantification of immunostains. The American Journal of Surgical Pathology, 25, 1204-1207.

Sangha, K. G., Kamalpreet K., Khera S.K., & Balwinder S. (2011). Toxicological Effects of Cypermethrin on Female Albino Rats. Toxicology International, 18, 5-8.

Shu, S., Ju, G., & Fan, L. (1988). The glucose oxidase-dabnickel in peroxidase histochemistry of the nervous system. Neuroscience Letters, 85, 169-171.

Singh, R., Letai, A., & Sarosiek, K. (2019). Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nature Reviews Molecular Cell Biology, 20, 175-193.

Soujanya, S., Lakshman, M., Kumar, A. A., & Reddy, A. G. (2013). Evaluation of the protective role of vitamin C in imidacloprid-induced hepatotoxicityin male Albino rats. Journal of Natural Science, Biology and Medicine, 4(1), 63-7.

Suvarna, K. S., Layton, C., & Bancroft, J. D. (2019). Bancroft’s theory and practice of histological techniques. E-Book, 8th edition. Elsevier Health Sciences,

Swelam, E. S., Abdallah, I. S., & Mossa, A. T. H. (2017). Ameliorating Effect of Zinc Against Oxidative Stress and Lipid Peroxidation Induced by Fipronil in Male Rats. Journal of Pharmacology and Toxicology, 12(1), 24-32.

Toghan, R., Amin, Y. A., Ali, R. A., Fouad, S. S., Ahmed, M. A. B., & Salih, S. M. M. (2022). Protective effects of Folic acid against reproductive, hematological, hepatic, and renal toxicity induced by Acetamiprid in male Albino rats. Toxicology, 469, 153115.

Wu, J., Wang, K., & Zhang, H. (2012). Dissipation and residue of acetamiprid in watermelon and soil in the open field. Bulletin of Environmental Contamination and Toxicology, 89, 644-648.

Yousef, H. N., Ibraheim, S. S., Ramadan, R. A., & Aboelwafa, H. R. (2022). The Ameliorative Role of Eugenol against Silver Nanoparticles-Induced Hepatotoxicity in Male Wistar Rats. Oxidative Medicine and Cellular Longevity, 2022, 3820848.

Zhu, Q. Y. (1989). Analysis of blood vessel invasion by cells of thyroid follicular carcinoma using image processing combined with immunohistochemistry. National Medical Journal of China, 69(10), 573-575

Zoumenou, B. G. Y. M., Aïna, M. P., Imorou. Toko, I., Igout, A., Douny, C., Brose, F., Schiffers, B., Gouda, I., Chabi Sika, K., Kestemont, P., & Scippo, M. L. (2019). Occurrence of Acetamiprid Residues in Water Reservoirs in the Cotton Basin of Northern Benin. Bulletin of Environmental Contamination and Toxicology, 102(1), 7-12.




How to Cite

Nur, G. (2024). The Effect of Acetamiprid Administration on Bcl-2 Immunoreactivity in the Liver. Turkish Journal of Agriculture - Food Science and Technology, 12(6), 940–947.



Research Paper