Bifenthrin Causes Kidney Damage via Induction of Oxidative Stress, Activation of Pro-Inflammatory Cytokines, and Up-Regulation of Apoptosis in Wistar Rats
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10.58578/ajbmbr.v1i1.3654
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Abstract
This study investigated the role of oxidative stress, inflammation, and apoptosis in bifenthrin-induced kidney damage in Wistar rat models. Adult male rats (110-300g) were divided into three groups of 10 rats each. Group 1 served as the normal control, while groups 2-3 were orally given 1 mg/ kg body weight bifenthrin for 14 and 28 days respectively. The results revealed that bifenthrin administration caused a significant (p<0.05) decrease in renal antioxidant enzymes such as superoxide dismutase, catalase, glutathione, glutathione S-transferase, and glutathione peroxidase. Conversely, malondialdehyde levels were significantly (p<0.05) increased. Pro-inflammatory cytokines TNF-α, IL1-β, IL-6, COX-2, iNOS, LTE B4, and PGE2 were significantly (p<0.05) elevated, highlighting an inflammatory response. Additionally, the apoptotic markers, caspase-3, and BAX were significantly (p<0.05) increased, while BCL-2, an anti-apoptotic protein, was significantly (p<0.05) decreased, indicating enhanced apoptosis. Renal function markers, creatinine, and urea were also significantly (p<0.05) elevated in bifenthrin-induced groups. Furthermore, the histopathology results revealed morphological damages in the kidneys of groups 2 and 3 animals These findings demonstrate bifenthrin's potential to cause significant oxidative stress, inflammation, apoptosis, and structural damage in renal tissues.
Keywords:
Kidney damage; Bifenthrin; Oxidative Stress; Apoptosis; Inflammation
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Ujong, U. P., & Ibor, M. E. (2024). Bifenthrin Causes Kidney Damage via Induction of Oxidative Stress, Activation of Pro-Inflammatory Cytokines, and Up-Regulation of Apoptosis in Wistar Rats. African Journal of Biochemistry and Molecular Biology Research, 1(1), 510-525. https://doi.org/10.58578/ajbmbr.v1i1.3654
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
References
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Miliopoulos, D., Gkouziouta, A., Leontiadis, E., & Adamopoulos, S. (2022). Cytokines and inflammatory markers. Oxford Textbook of Heart Failure, 193.
Mohammadi, H., Ghassemi-Barghi, N., Malakshah, O., & Ashari, S. (2019). Pyrethroid exposure and neurotoxicity: a mechanistic approach. Archives of Industrial Hygiene and Toxicology, 70(2), 74-89.
Morales, M., & Munné-Bosch, S. (2019). Malondialdehyde: facts and artifacts. Plant physiology, 180(3), 1246-1250.
Nuhu, F., Gordon, A., Sturmey, R., Seymour, A. M., & Bhandari, S. (2020). Measurement of glutathione as a tool for oxidative stress studies by high performance liquid chromatography. Molecules, 25(18), 4196.
Pylak-Piwko, O., & Nieradko-Iwanicka, B. (2021). Subacute poisoning with bifenthrin increases the level of interleukin 1ß in mice kidneys and livers. BMC Pharmacology and Toxicology, 22(1), 21.
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Rogeri, P. S., Gasparini, S. O., Martins, G. L., Costa, L. K. F., Araujo, C. C., Lugaresi, R., & Lancha Jr, A. H. (2020). Crosstalk between skeletal muscle and immune system: which roles do IL-6 and glutamine play?. Frontiers in physiology, 11, 582258.
Rubio-Riquelme, N., Huerta-Retamal, N., Gómez-Torres, M. J., & Martínez-Espinosa, R. M. (2020). Catalase as a molecular target for male infertility diagnosis and monitoring: An overview. Antioxidants, 9(1), 78.
Sachdev, S., Ansari, S. A., Ansari, M. I., Fujita, M., & Hasanuzzaman, M. (2021). Abiotic stress and reactive oxygen species: Generation, signaling, and defense mechanisms. Antioxidants, 10(2), 277.
Saini, R., & Singh, S. (2019). Inducible nitric oxide synthase: An asset to neutrophils. Journal of leukocyte biology, 105(1), 49-61.
Sasaki, F., & Yokomizo, T. (2019). The leukotriene receptors as therapeutic targets of inflammatory diseases. International immunology, 31(9), 607-615.
Schult, L., Halbgebauer, R., Karasu, E., & Huber-Lang, M. (2023). Glomerular injury after trauma, burn, and sepsis. Journal of Nephrology, 36(9), 2417-2429.
Singh, S., Mukherjee, A., Jaiswal, D. K., de Araujo Pereira, A. P., Prasad, R., Sharma, M., & Verma, J. P. (2022). Advances and future prospects of pyrethroids: Toxicity and microbial degradation. Science of the Total Environment, 829, 154561.
Soliman, M. M., Aldhahrani, A., Gaber, A., Alsanie, W. F., Mohamed, W. A., Metwally, M. M., ... & Shukry, M. (2022). Ameliorative impacts of chrysin against gibberellic acid-induced liver and kidney damage through the regulation of antioxidants, oxidative stress, inflammatory cytokines, and apoptosis biomarkers. Toxicology Research, 11(1), 235-244.
Ursini, F., & Maiorino, M. (2020). Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radical Biology and Medicine, 152, 175-185.
Vašková, J., Kočan, L., Vaško, L., & Perjési, P. (2023). Glutathione-related enzymes and proteins: A review. Molecules, 28(3), 1447.
Vistisen, D., Andersen, G. S., Hulman, A., Persson, F., Rossing, P., & Jørgensen, M. E. (2019). Progressive decline in estimated glomerular filtration rate in patients with diabetes after moderate loss in kidney function—even without albuminuria. Diabetes Care, 42(10), 1886-1894.
Wang, T., & He, C. (2020). TNF-α and IL-6: the link between immune and bone system. Current drug targets, 21(3), 213-227.
Wang, X., Cheng, X., Liu, H., Mu, X., & Zheng, H. (2024). Food nutrition and toxicology targeting on specific organs in the era of single-cell sequencing. Food Science and Human Wellness, 13(1), 75-89.
Yadav, D., Rangabhashiyam, S., Verma, P., Singh, P., Devi, P., Kumar, P., ... & Kumar, K. S. (2021). Environmental and health impacts of contaminants of emerging concerns: Recent treatment challenges and approaches. Chemosphere, 272, 129492.
Yao, C., & Narumiya, S. (2019). Prostaglandin‐cytokine crosstalk in chronic inflammation. British journal of pharmacology, 176(3), 337-354.
Ahmed, A. Y., Aowda, S. A., & Hadwan, M. H. (2021). A validated method to assess glutathione peroxidase enzyme activity. Chemical Papers, 75, 6625-6637.
Aouey, B., Derbali, M., Chtourou, Y., Bouchard, M., Khabir, A., & Fetoui, H. (2017). Pyrethroid insecticide lambda-cyhalothrin and its metabolites induce liver injury through the activation of oxidative stress and proinflammatory gene expression in rats following acute and subchronic exposure. Environmental Science and Pollution Research, 24, 5841-5856.
Araya, L. E., Soni, I. V., Hardy, J. A., & Julien, O. (2021). Deorphanizing caspase-3 and caspase-9 substrates in and out of apoptosis with deep substrate profiling. ACS Chemical Biology, 16(11), 2280-2296.
Bhatia, K., Misra, P., Singh, A., Mukherjee, B., & Ambade, V. N. (2019). Study of blood urea nitrogen (bun), serum creatinine in diabetic and non-diabetic patients in a tertiary care hospital. Int J Med Biomed Stud, 3(4), 180-6.
Buratti, F. M., Darney, K., Vichi, S., Turco, L., Di Consiglio, E., Lautz, L. S., & Testai, E. (2021). Human variability in glutathione-S-transferase activities, tissue distribution and major polymorphic variants: Meta-analysis and implication for chemical risk assessment. Toxicology Letters, 337, 78-90.
Calabriso, N., Massaro, M., Scoditti, E., Carluccio, C., Verri, T., & Carluccio, M. A. (2023). Epigenetic mechanisms in vascular inflammation: modulation of endothelial adhesion molecules and endothelium-leukocyte adhesion. Frontiers in Bioscience-Landmark, 28(9), 194.
Chota, A., George, B. P., & Abrahamse, H. (2021). Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death. Oncotarget, 12(16), 1615.
Dar, M. A., Khan, A. M., Raina, R., Verma, P. K. & Wani, N. M. (2019) Effect of bifenthrin on oxidative stress parameters in the liver, kidneys, and lungs of rats. Environ. Sci. Pollut. Res. 26, 9365–9370.
Diaz-Ricart, M., Torramade-Moix, S., Pascual, G., Palomo, M., Moreno-Castaño, A. B., Martinez-Sanchez, J., & Escolar, G. (2020). Endothelial damage, inflammation and immunity in chronic kidney disease. Toxins, 12(6), 361.
Ferrer, M. D., Busquets-Cortés, C., Capó, X., Tejada, S., Tur, J. A., Pons, A., & Sureda, A. (2019). Cyclooxygenase-2 inhibitors as a therapeutic target in inflammatory diseases. Current medicinal chemistry, 26(18), 3225-3241.
Georgiou-Siafis, S. K., & Tsiftsoglou, A. S. (2023). The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates. Antioxidants, 12(11), 1953.
Jiang, M., Qi, L., Li, L., & Li, Y. (2020). The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell death discovery, 6(1), 112.
Juan, C. A., Pérez de la Lastra, J. M., Plou, F. J., & Pérez-Lebeña, E. (2021). The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. International journal of molecular sciences, 22(9), 4642.
Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in inflammatory disease. International journal of molecular sciences, 20(23), 6008.
Kucukler, S., Benzer, F., Yildirim, S., Gur, C., Kandemir, F. M., Bengu, A. S., ... & Dortbudak, M. B. (2021). Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biological Trace Element Research, 199(4), 1501-1514.
Liakopoulos, V., Roumeliotis, S., Zarogiannis, S., Eleftheriadis, T., & Mertens, P. R. (2019, January). Oxidative stress in hemodialysis: Causative mechanisms, clinical implications, and possible therapeutic interventions. In Seminars in dialysis (Vol. 32, No. 1, pp. 58-71).
Liu, Y., Zhang, Y., Liu, Q., Wang, Q., Lin, A., Luo, J., & Wei, H. (2021). In vitro measurement of superoxide dismutase-like nanozyme activity: a comparative study. Analyst, 146(6), 1872-1879.
Madkour, L. H. (2019). Function of reactive oxygen species (ROS) inside the living organisms and sources of oxidants. Pharm. Sci. Anal. Res. J, 2, 180023.
Migliorini, P., Italiani, P., Pratesi, F., Puxeddu, I., & Boraschi, D. (2020). The IL-1 family cytokines and receptors in autoimmune diseases. Autoimmunity reviews, 19(9), 102617.
Miliopoulos, D., Gkouziouta, A., Leontiadis, E., & Adamopoulos, S. (2022). Cytokines and inflammatory markers. Oxford Textbook of Heart Failure, 193.
Mohammadi, H., Ghassemi-Barghi, N., Malakshah, O., & Ashari, S. (2019). Pyrethroid exposure and neurotoxicity: a mechanistic approach. Archives of Industrial Hygiene and Toxicology, 70(2), 74-89.
Morales, M., & Munné-Bosch, S. (2019). Malondialdehyde: facts and artifacts. Plant physiology, 180(3), 1246-1250.
Nuhu, F., Gordon, A., Sturmey, R., Seymour, A. M., & Bhandari, S. (2020). Measurement of glutathione as a tool for oxidative stress studies by high performance liquid chromatography. Molecules, 25(18), 4196.
Pylak-Piwko, O., & Nieradko-Iwanicka, B. (2021). Subacute poisoning with bifenthrin increases the level of interleukin 1ß in mice kidneys and livers. BMC Pharmacology and Toxicology, 22(1), 21.
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.
Rogeri, P. S., Gasparini, S. O., Martins, G. L., Costa, L. K. F., Araujo, C. C., Lugaresi, R., & Lancha Jr, A. H. (2020). Crosstalk between skeletal muscle and immune system: which roles do IL-6 and glutamine play?. Frontiers in physiology, 11, 582258.
Rubio-Riquelme, N., Huerta-Retamal, N., Gómez-Torres, M. J., & Martínez-Espinosa, R. M. (2020). Catalase as a molecular target for male infertility diagnosis and monitoring: An overview. Antioxidants, 9(1), 78.
Sachdev, S., Ansari, S. A., Ansari, M. I., Fujita, M., & Hasanuzzaman, M. (2021). Abiotic stress and reactive oxygen species: Generation, signaling, and defense mechanisms. Antioxidants, 10(2), 277.
Saini, R., & Singh, S. (2019). Inducible nitric oxide synthase: An asset to neutrophils. Journal of leukocyte biology, 105(1), 49-61.
Sasaki, F., & Yokomizo, T. (2019). The leukotriene receptors as therapeutic targets of inflammatory diseases. International immunology, 31(9), 607-615.
Schult, L., Halbgebauer, R., Karasu, E., & Huber-Lang, M. (2023). Glomerular injury after trauma, burn, and sepsis. Journal of Nephrology, 36(9), 2417-2429.
Singh, S., Mukherjee, A., Jaiswal, D. K., de Araujo Pereira, A. P., Prasad, R., Sharma, M., & Verma, J. P. (2022). Advances and future prospects of pyrethroids: Toxicity and microbial degradation. Science of the Total Environment, 829, 154561.
Soliman, M. M., Aldhahrani, A., Gaber, A., Alsanie, W. F., Mohamed, W. A., Metwally, M. M., ... & Shukry, M. (2022). Ameliorative impacts of chrysin against gibberellic acid-induced liver and kidney damage through the regulation of antioxidants, oxidative stress, inflammatory cytokines, and apoptosis biomarkers. Toxicology Research, 11(1), 235-244.
Ursini, F., & Maiorino, M. (2020). Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radical Biology and Medicine, 152, 175-185.
Vašková, J., Kočan, L., Vaško, L., & Perjési, P. (2023). Glutathione-related enzymes and proteins: A review. Molecules, 28(3), 1447.
Vistisen, D., Andersen, G. S., Hulman, A., Persson, F., Rossing, P., & Jørgensen, M. E. (2019). Progressive decline in estimated glomerular filtration rate in patients with diabetes after moderate loss in kidney function—even without albuminuria. Diabetes Care, 42(10), 1886-1894.
Wang, T., & He, C. (2020). TNF-α and IL-6: the link between immune and bone system. Current drug targets, 21(3), 213-227.
Wang, X., Cheng, X., Liu, H., Mu, X., & Zheng, H. (2024). Food nutrition and toxicology targeting on specific organs in the era of single-cell sequencing. Food Science and Human Wellness, 13(1), 75-89.
Yadav, D., Rangabhashiyam, S., Verma, P., Singh, P., Devi, P., Kumar, P., ... & Kumar, K. S. (2021). Environmental and health impacts of contaminants of emerging concerns: Recent treatment challenges and approaches. Chemosphere, 272, 129492.
Yao, C., & Narumiya, S. (2019). Prostaglandin‐cytokine crosstalk in chronic inflammation. British journal of pharmacology, 176(3), 337-354.
