Kuersetin'in Sipermetrin Kaynaklı Mide Hasarı Üzerine Etkileri: Oksidatif Stres, Enflamasyon ve Apoptozun Rolü

Year 2023, Volume: 12 Issue: 2, 556 - 566, 18.06.2023

Nurhan Akaras Cihan Gür Hasan Şimşek Sibel Çiğdem Tuncer

https://doi.org/10.37989/gumussagbil.1225539

Cited By: 1

Abstract

Bu çalışma, ratlarda sipermetrin (CYP) kaynaklı gastrotoksisite üzerine kuersetin'in (QUE) etkilerini araştırmak için yapıldı. 35 adet Sprague Dawley ratı, her grupta 7 tane olacak şekilde rastgele beş gruba ayrıldı. Çalışmada, ratlara 28 gün boyunca 25 mg/kg sipermetrin uygulandıktan 30 dakika sonra oral olarak 25 ve 50 mg/kg QUE verildi. Mide dokularında oksidatif stres, inflamasyon, ER stres, apoptoz ve otofaji belirteçleri biyokimyasal olarak analiz edildi. Ayrıca mide dokusu mikroskobik değerlendirme için histolojik analiz yapıldı. Sonuçlar, QUE'nin CYP kaynaklı lipit peroksidasyonunu (MDA) düşürerek ve GSH, SOD, KAT ve GPx aktivitelerini artırarak doku hasarını önlediğini ortaya koydu. Ayrıca NF-𝜅B, IL-1β, TNF-α, iNOS ve COX-2 gibi inflamatuar belirteçleri baskılayarak anti-inflamatuar etki gösterdi. CYP kaynaklı artan PERK, ATF6, Kaspaz-3 ve Beklin-1 belirteçlerini QUE uygulanması aşağı regüle etti. Ek olarak, CYP’ye bağlı olarak oluşan mide dokusundaki patolojik doku hasarını QUE verilmesi iyileştirdi. Bu çalışmanın verileri Que nin oksidatif stresi, enflamasyonu, ER stresi, apoptozu ve otofajiyi iyileştirerek CYP kaynaklı mide toksisitesini baskıladığını göstermektedir.

Keywords

Gastrotoksisite, Kuersetin, Oksidatif Stres, Rat, Sipermetrin

Supporting Institution

Destekleyen bir kurum yoktur.

Effects of Quercetin on Cypermethrin-Induced Stomach Injury: The Role of Oxidative Stress, Inflammation, and Apoptosis.

Abstract

This study was conducted to investigate the effects of quercetin (QUE) on cypermethrin (CYP) induced gastrotoxicity in rats. 35 Sprague-Dawley rats were randomly divided into five groups, 7 in each group. In the study, 25 and 50 mg/kg QUE were administered orally 30 min after 25 mg/kg cypermethrin was administered to rats for 28 days. Oxidative stress, inflammation, ER stress, apoptosis and autophagy markers were biochemically analyzed in gastric tissues. Additionally, histological analysis was performed for microscopic evaluation of gastric tissue. The results revealed that QUE prevented tissue damage by reducing CYP-induced lipid peroxidation (MDA) and increasing GSH, SOD, CAT and GPx activities. It also showed anti-inflammatory effect by suppressing inflammatory markers such as NF-𝜅B, IL-1β, TNF-α, iNOS and COX-2. QUE administration down-regulated CYP-induced increased PERK, ATF6, Caspase-3 and Beclin-1 markers. In addition, administration of QUE ameliorated the pathological tissue damage in gastric tissue due to CYP. The data of this study show that Que suppresses CYP-induced gastric toxicity by reducing oxidative stress, inflammation, ER stress, apoptosis a autophagy.

Keywords

Cypermethrin, Gastrotoxicity, Oxidative Stress, Quercetin, Rat

References

• 1. Zhou, L, Zhou, M, Tan, H. and Xiao, M. (2020). ‘’Cypermethrin-İnduced Cortical Neurons Apoptosis Via The Nrf2/ARE Signaling Pathway’’. Pesticide Biochemistry and Physiology, 165, 104547.
• 2. Cunha, E.O, Reis, A.D, Macedo, M.B, Machado, M.S. and Dallegrave, E. (2020). ‘’Ototoxicity of Cypermethrin in Wistar Rats’’. Brazilian Journal of Otorhinolaryngology, 86, 587-592.
• 3. Copplestone, J.F. (1988). ‘’The Development of the WHO Recommended Classification of Pesticides by Hazard’’. Bulletin of the World Health Organization, 66 (5), 545.
• 4. Liu, L, Hu, J.X, Wang, H, Chen, B.J, He, Z. and Xu, L.C. (2010). ‘’Effects of Beta-Cypermethrin on Male Rat Reproductive System’’. Environmental Toxicology and Pharmacology, 30 (3), 251-256.
• 5. Yadav, A, Tandon, A, Seth, B, Goyal, S, Singh, S.J, Tiwari, S.K. and Chaturvedi, R.K. (2021). ‘’Cypermethrin Impairs Hippocampal Neurogenesis and Cognitive Functions by Altering Neural Fate Decisions in the Rat Brain’’. Molecular Neurobiology, 58 (1), 263-280.
• 6. Soliman, M.M, Attia, H.F. and El-Ella, G.A. (2015). Genetic and Histopathological Alterations Induced by Cypermethrin in Rat Kidney and Liver: Protection by Sesame Oil. International Journal of Immunopathology and Pharmacology, 28 (4), 508-520.
• 7. Sharma, P, Huq, A.U. and Singh, R. (2014). ‘’Cypermethrin-Induced Reproductive Toxicity in the Rat is Prevented by Resveratrol’’. Journal of Human Reproductive Sciences, 7 (2), 99.
• 8. Taha, M.A, Badawy, M.E, Abdel-Razik, R.K, Younis, H M. and Abo-El-Saad, M.M. (2021). ‘’Mitochondrial Dysfunction and Oxidative Stress in Liver of Male Albino Rats After Exposing to Sub-Chronic Intoxication of Chlorpyrifos, Cypermethrin, and Imidacloprid’’. Pesticide Biochemistry and Physiology, 178, 104938.
• 9. Agrawal, S, Singh, A, Tripathi, P, Mishra, M, Singh, P. K. and Singh, M.P. (2015). ‘’Cypermethrin-Induced Nigrostriatal Dopaminergic Neurodegeneration Alters the Mitochondrial Function: A Proteomics Study’’. Molecular Neurobiology, 51 (2), 448-465.
• 10. Ileriturk, M, Kandemir, O. and Kandemir, F.M. (2022). ‘’Evaluation of Protective Effects of Quercetin Against Cypermethrin‐Induced Lung Toxicity in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Endoplasmic Reticulum Stress Pathway’’. Environmental Toxicology, 37 (11), 2639-2650.
• 11. Ali, H.F, El-Sayed, N.M, Ahmed, A.A, Hanna, P.A. and Moustafa, Y.M. (2020). ‘’Nano Selenium Ameliorates Oxidative Stress and Inflammatory Response Associated with Cypermethrin-Induced Neurotoxicity in Rats’’. Ecotoxicology and Environmental Safety, 195, 110479.
• 12. Nakhaee, S, Farrokhfall, K, Miri-Moghaddam, E, Foadoddini, M, Askari, M. and Mehrpour, O. (2021). ‘’The Effects of Quercetin on Seizure, Inflammation Parameters and Oxidative Stress in Acute on Chronic Tramadol Intoxication’’. BMC Pharmacology and Toxicology, 22 (1), 1-11.
• 13. Roslan, J, Giribabu, N, Karim, K. and Salleh, N. (2017). ‘’Quercetin Ameliorates Oxidative Stress, Inflammation and Apoptosis in the Heart of Streptozotocin-Nicotinamide-Induced Adult Male Diabetic Rats’’. Biomedicine & Pharmacotherapy, 86, 570-582.
• 14. Semis, H.S, Gur, C, Ileriturk, M, Kandemir, F.M. and Kaynar, O. (2022) ‘’Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases. Am J Sports Med, 50 (2), 486-498.
• 15. Çomaklı, S, Özdemir, S, Küçükler, S. and Kandemir, F.M. (2023). ‘’Beneficial Effects of Quercetin on Vincristine-Induced Liver Injury in Rats: Modulating the Levels of Nrf2/HO-1, NF-kB/STAT3, and SIRT1/PGC-1α’’. J Biochem Mol Toxicol, e23326. doi:10.1002/jbt.23326.
• 16. Zheng, S, Ma, M, Chen, Y. and Li, M. (2022). ‘’Effects of Quercetin on Ovarian Function and Regulation of the Ovarian PI3K/Akt/Foxo3a Signalling Pathway and Oxidative Stress in A Rat Model of Cyclophosphamide‐Induced Premature Ovarian Failure’’. Basic & Clinical Pharmacology & Toxicology, 130 (2), 240-253.
• 17. Placer, Z.A, Cushman, L.L. and Johnson, B.C. (1966). ‘’Estimation of Product of Lipid Peroxidation (Malonyl dialdehyde) in Biochemical Systems’’. Analytical biochemistry, 16 (2), 359-364.
• 18. Sun, Y.I, Oberley, L.W. and Li, Y. (1988). ‘’A Simple Method for Clinical Assay of Superoxide Dismutase’’. Clinical Chemistry, 34 (3), 497-500.
• 19. Aebi, H. (1984). ‘’Catalase In Vitro. In Methods in Enzymology’’. Academic Press, 105, 121-126.
• 20. Sedlak, J. and Lindsay, R.H. (1968). ‘’Estimation of Total, Protein-Bound and Nonprotein Sulfhydryl Groups in Tissue with Ellman's Reagent’’. Analytical Biochemistry, 25, 192-205.
• 21. Lawrence, R.A. and Burk, R.F. (1976). ‘’Glutathione Peroxidase Activity İn Selenium-Deficient Rat Liver’’. Biochemical and Biophysical Research Communications, 71(4), 952-958.
• 22. Lowry O.H, Rosebrough N.J, Farr A.L. and Randall R.J. (1951). ‘’Protein Measurement with the Folin Phenol Reagent’’. J Biol Chem, 193 (1), 265-275.
• 23. Livak, K.J. and Schmittgen, T.D. (2001). ‘’Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2− ΔΔCT Method’’. Methods, 25 (4), 402-8.
• 24. Wang, H, X, Zhang, R, Li, Z, Wang, L.S, Yu, Y, Wang, Q. and Xu, L.C. (2021). ‘’Cypermethrin Induces Sertoli Cell Apoptosis Through Mitochondrial Pathway Associated with Calcium’’. Toxicology Research, 10 (4), 742-750.
• 25. Behnami, F, Yousefinejad, S, Jafari, S, Neghab, M. and Soleimani, E. (2021). ‘’Assessment of Respiratory Exposure to Cypermethrin among Farmers and Farm Workers of Shiraz, Iran’’. Environmental Monitoring and Assessment, 193 (4), 1-10.
• 26. Li, B, Wang, Y, Zhao, H, Yin, K, Liu, Y, Wang, D. and Xing, M. (2022). ‘’Oxidative Stress is Involved in the Activation of NF-Κb Signal Pathway and Immune Inflammatory Response in Grass Carp Gill Induced by Cypermethrin and/or Sulfamethoxazole’’. Environmental Science and Pollution Research, 29 (13), 19594-19607.
• 27. Li, J, Sun, B.X, Wang, D.L, Liu, Y, Qi, J.J, Nie, X.W. and Liang, S. (2021). ‘’Melatonin Ameliorates Cypermethrin-Induced Impairments by Regulating Oxidative Stress, DNA Damage and Apoptosis in Porcine Sertoli Cells’’. Theriogenology, 167, 67-76.
• 28. Mezni, A, Mhadhbi, L, Khazri, A, Sellami, B, Dellali, M, Mahmoudi, E. and Beyrem, H. (2020). ‘’The Protective Effect of Hibiscus Sabdariffa Calyxes Extract Against Cypermethrin Induced Oxidative Stress in Mice’’. Pesticide Biochemistry and Physiology, 165, 104463.
• 29. Ghorzi, H, Merzouk, H, Hocine, L. and Merzouk, S.A. (2017). ‘’Long Term Biochemical Changes in Offspring of Rats Fed Diet Containing Alpha-Cypermethrin’’. Pesticide Biochemistry and Physiology, 142, 133-140.
• 30. Akaras, N, Abuc, O.O, Koc, K, Bal, T, Geyikoglu, F, Atilay, H. and Gul, M. (2020). ‘’(1→ 3)‐β‐d‐Glucan Enhances the Toxicity Induced by Bortezomib in Rat Testis’’. Journal of Food Biochemistry, 44 (3), E13155.
• 31. Gur, C, Kandemir, F.M, Caglayan. and C, Satıcı E. (2022). ‘‘Chemopreventive Effects of Hesperidin Against Paclitaxel-İnduced Hepatotoxicity and Nephrotoxicity via Amendment of Nrf2/HO-1 and Caspase-3/Bax/Bcl-2 Signaling Pathways’’. Chem Biol Interact, 365, 110073.
• 32. Jin, Y, Zheng, S, Pu, Y, Shu, L, Sun, L, Liu, W. and Fu, Z. (2011). ‘‘Cypermethrin has the Potential to Induce Hepatic Oxidative Stress, DNA Damage and Apoptosis in Adult Zebrafish (Danio Rerio)’’. Chemosphere, 82 (3), 398-404.
• 33. Ahmed, O.M, Elkomy, M.H, Fahim, H.I, Ashour, M.B, Naguib, I.A, Alghamdi, B.S. and Ahmed, N.A. (2022). ‘‘Rutin and Quercetin Counter Doxorubicin-Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2’’. Oxidative Medicine and Cellular Longevity, doi: 10.1155/2022/2710607.
• 34. Kandemir, F.M, Yıldırım, S, Kucukler, S, Caglayan, C, Darendelioğlu, E. and Dortbudak M.B. (2020). ‘‘Protective Effects of Morin Against Acrylamide-İnduced Hepatotoxicity and Nephrotoxicity: A Multi-Biomarker Approach’’. Food Chem Toxicol, 138, 111190.
• 35. Arafa, M.H, Mohamed, D.A. and Atteia, H.H. (2015). ‘‘Ameliorative Effect of N‐Acetyl Cysteine on Alpha‐Cypermethrin‐İnduced Pulmonary Toxicity in Male Rats’’. Environmental Toxicology, 30 (1), 26-43.
• 36. Kandemir, F.M, Ileriturk, M. and Gur, C. (2022). ‘‘Rutin Protects Rat Liver and Kidney from Sodium Valproate-Induce Damage by Attenuating Oxidative Stress, ER Stress, Inflammation, Apoptosis and Autophagy’’. Molecular Biology Reports, 1-12.
• 37. Yardim, A, Kandemir, F.M, Ozdemir, S, Kucukler, S, Comakli, S, Gur, C. and Celik, H. (2020). ‘‘Quercetin Provides Protection Against the Peripheral Nerve Damage Caused by Vincristine in Rats by Suppressing Caspase 3, NF-Κb, ATF-6 Pathways and Activating Nrf2, Akt Pathways’’. Neurotoxicology, 81, 137-146.
• 38. Gur, C. and Kandemir, F.M. (2023). ‘‘Molecular and Biochemical Investigation of the Protective Effects of Rutin against Liver and Kidney Toxicity Caused by Malathion Administration in A Rat Model’’. Environ Toxicol, (3), 555-565. doi:10.1002/tox.23700.
• 39. Akaras, N, Gur, C, Kucukler, S. and Kandemir F.M. (2023). ‘‘Zingerone Reduces Sodium Arsenite-Induced Nephrotoxicity by Regulating Oxidative Stress, Inflammation, Apoptosis and Histopathological Changes’’. Chem Biol Interact, 374, 110410. doi:10.1016/j.cbi.2023.110410
• 40. Küçükler, S, Kandemir, F.M, Özdemir, S, Çomaklı, S. and Caglayan, C. (2021). ‘‘Protective Effects of Rutin against Deltamethrin-Induced Hepatotoxicity and Nephrotoxicity in Rats via Regulation of Oxidative Stress, Inflammation, and Apoptosis’’. Environ Sci Pollut Res Int, 28 (44), 62975-62990.