Investigating Potential Protective Effects of Rutin against Deltametrin-Induced Spleen Toxicity in Rats through Oxidative Stress, Apoptosis and Inflammation Markers

Yıl 2022, Cilt: 17 Sayı: 1, 6 - 10, 29.04.2022

Cihan Gür Aydın Genç Özge Kandemir

Öz

In this study, the protective effects of rutin (RUT) against spleen toxicity caused by deltamethrin (DLM) were investigated. For this purpose, DLM and/or RUT were applied to Sprague dawley rats for 28 days. According to results, DLM increased malondialdehyde (MDA) levels in spleen tissue, decreased glutathione (GSH) levels and mRNA transcript levels of superoxide dismutase (SOD), catalase (KAT) and glutathione peroxidase (GPx) enzymes. RUT treatment caused a decrease in MDA levels, activated SOD, KAT and GPx expressions and increased GSH levels. Also, RUT showed anti-inflammatory effect in spleen tissue by suppressing the expressions of mitogen-activated protein kinase-14 (MAPK14), nuclear factor kappa-B (NF-ĸB) and interleukin-1-beta (IL-1β) activated by DLM. It was observed that the expression of anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) suppressed by DLM was activated by RUT. It is also among the other findings that the apoptotic protein Bcl-2-related X protein (Bax) is activated by DLM and suppressed by RUT. As a result, it was determined that DLM had a toxic effect on spleen tissue by causing oxidative stress, inflammation and apoptosis, however, RUT demonstrated antioxidant, anti-inflammatory and anti-apoptotic effects and protected spleen tissue from the toxic effect of DLM.

Anahtar Kelimeler

Oxidative stress, Inflammation, Apoptosis, Deltamethrin, Rutin

Ratlarda Deltametrin’in Neden Olduğu Dalak Toksisitesine Karşı Rutin’in Potansiyel Koruyucu Etkilerinin Oksidatif Stres, Apoptoz ve İnflamasyon Belirteçleri Üzerinden Araştırılması

Öz

Çalışmada deltametrinin (DLM) meydana getirdiği dalak toksisitesine karşı rutin’in (RUT) koruyucu etkileri araştırılmıştır. Bu amaçla çalışmada Sprague dawley ratlara 28 gün boyunca DLM ve/veya RUT uygulandı. DLM’nin dalak dokusunda malondialdehit (MDA) seviyelerini arttırdığı, glutatyon (GSH) seviyelerini ve süperoksit dismutaz (SOD), katalaz (KAT) ve glutatyon peroksidaz (GPx) enzimlerinin mRNA transkript seviyelerini ise azalttığı belirlendi. RUT tedavisinin ise MDA seviyelerinde azalma meydana getirdiği, SOD, KAT ve GPx ekspresyonlarını aktive ettiği ve GSH seviyelerini arttırdığı görüldü. Ayrıca RUT’un DLM tarafından aktive edilen mitojenle aktifleştirilen protein kinaz 14 (MAPK14), nükleer faktör kappa B (NF-ĸB) ve interlökin 1 beta (IL-1β) ekspresyonlarını baskılayarak dalak dokusunda anti-enflamatuar etki gösterdiği belirlendi. DLM tarafından baskılanan anti-apoptotik protein B hücreli lenfoma-2 (Bcl-2) ekspresyonunun RUT tarafından aktive edildiği görüldü. Ayrıca apoptotik protein olan Bcl-2 ile ilişkili X proteininin (Bax) DLM tarafından aktive edildiği, RUT tarafından ise baskılandığı elde edilen diğer bulgulardandır. Sonuç olarak DLM’nin oksidatif strese, enflamasyona ve apoptoza neden olarak dalak dokusunda toksik etki gösterdiği bununla birlikte RUT’un antioksidan, anti-enflamatuar ve anti-apoptotik etki göstererek dalak dokusunu DLM’nin toksik etkisinden koruduğu belirlendi.

Anahtar Kelimeler

Oksidatif stres, İnflamasyon, Apoptoz, Deltametrin, Rutin

Kaynakça

• 1. Ahmadipour A, Sharififar F, Pournamdari M, et al. Hepatoprotective effect of Zataria Multiflora Boiss against malathion-induced oxidative stress in male rats. Orient Pharm Exp Med. 2016;16:287-293. [Crossref]
• 2. Bhardwaj JK, Saraf P. Malathion-induced granulosa cell apoptosis in caprine antral follicles: an ultrastructural and flow cytometric analysis. Microsc Microanal. 2014;20(6):1861-1868. [Crossref]
• 3. Abdel-Daim MM, Abuzead SM, Halawa SM. Protective role of Spirulina platensis against acute deltamethrin-induced toxicity in rats. PloS One. 2013;8:e72991. [Crossref]
• 4. Lu Q, Sun Y, Ares I, et al. Deltamethrin toxicity: A review of oxidative stress and metabolism. Environ Res. 2019;170:260-281. [Crossref]
• 5. Maalej A, Mahmoudi A, Bouallagui Z, Fki I, Marrekchi R, Sayadi S. Olive phenolic compounds attenuate deltamethrin-induced liver and kidney toxicity through regulating oxidative stress, inflammation and apoptosis. Food Chem Toxicol. 2017;106:455-465. [Crossref]
• 6. Jindal R, Sinha R, Brar P. Evaluating the protective efficacy of Silybum marianum against deltamethrin induced hepatotoxicity in piscine model. Environ Toxicol Pharmacol. 2019;66:62-68. [Crossref]
• 7. Bagherpour H, Malekshah AK, Amiri FT, Azadbakht M. Protective effect of green tea extract on the deltamethrin-induced toxicity in mice testis: An experimental study. Int J Reprod Biomed. 2018;17(5):337-348. [Crossref]
• 8. Aksu EH, Kandemir FM, Küçükler S. Ameliorative effect of hesperidin on streptozotocin-diabetes mellitus-induced testicular DNA damage and sperm quality degradation in Sprague-Dawley rats. J Food Biochem. 2021;45(10):e13938. [Crossref]
• 9. Caglayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sci. 2021;281:119730. [Crossref]
• 10. Gur C, Kandemir FM, Darendelioglu E, et al. Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environ Sci Pollut Res. 2021;28:49808-49819. [Crossref]
• 11. Kucukler S, Benzer F, Yildirim S, et al. Protective effects of chrysin against oxidative stress and inflammation induced by lead acetate in rat kidneys: a biochemical and histopathological approach. Biol Trace Elem Res. 2021;199:1501-1514. [Crossref]
• 12. Yardim A, Kandemir FM, Ozdemir S, et al. 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. 2020;81:137-146. [Crossref]
• 13. Kandemir FM, Caglayan C, Aksu EH, et al. Protective effect of rutin on mercuric chloride-induced reproductive damage in male rats. Andrologia. 2020;52(3):e13524. [Crossref]
• 14. Kandemir FM, Hanedan B, Aktaş MS, Küçükler S, Çağlayan C. Ratlarda Sisplatinden Kaynaklanan Nefrotoksisite Üzerine Rutinin İyileştirici Etkileri. Fırat Univ Vet J Health Sci. 2020;34:147-151.
• 15. Genc M, Kandemir F, Coban O. Effects of In-Ovo Rutin Injection to Fertile Japanese Quail (Coturnix Coturnix Japonica) Egg on Hatchability, Embryonic Death, Hatchling Weight, and Hatchling Liver Oxidative and Nitrosative Stress. Braz J Poult Sci. 2019;21(1): DOI:10.1590/1806-9061-2018-0786. [Crossref]
• 16. Caglayan C, Kandemir FM, Darendelioğlu E, Yıldırım S, Kucukler S, Dortbudak MB. Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. Biol Trace Elem Res. 2019;56:60-68. [Crossref]
• 17. Caglayan C, Kandemir FM, Yildirim S, Kucukler S, Eser G. Rutin protects mercuric chloride-induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. Biol Trace Elem Res. 2019;54:69-78. [Crossref]
• 18. Aktaş MS, Kandemir FM, Özkaraca M, Hanedan B, Kırbaş A. Protective effects of rutin on acute lung injury induced by oleic acid in rats. Kafkas Univ Vet Fak Derg. 2017;23(3):443-451.
• 19. Aksu E, Kandemir F, Özkaraca M, Ömür A, Küçükler S, Çomaklı S. Rutin ameliorates cisplatin-induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats. Andrologia. 2017;49:e12593. [Crossref]
• 20. Kandemir FM, Ozkaraca M, Yildirim BA, et al. Rutin attenuates gentamicin- induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats. Renal Failure. 2015;37(3):518-525. [Crossref]
• 21. Manzoni AG, Passos DF, da Silva JL, et al. Rutin and curcumin reduce inflammation, triglyceride levels and ADA activity in serum and immune cells in a model of hyperlipidemia. Blood Cells Mol Dis. 2019;76:13-21. [Crossref]
• 22. Yousef MI, Awad TI, Mohamed EH. Deltamethrin-induced oxidative damage and biochemical alterations in rat and its attenuation by Vitamin E. Toxicology. 2006;227(3):240-247. [Crossref]
• 23. Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-364. [Crossref]
• 24. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25(1):192-205. [Crossref]
• 25. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-408. [Crossref]
• 26. El-Shenawy NS. Effects of insecticides fenitrothion, endosulfan and abamectin on antioxidant parameters of isolated rat hepatocytes. Toxicol in Vitro. 2010;24(4):1148-1157. [Crossref]
• 27. Gur C, Kandemir FM, Aydın G. Bortezomib ile kalp hasarı oluşturulan ratlarda berberinin oksidatif ve nitrozatif stres üzerine etkisi. Türk Doğa ve Fen Dergisi. 2020;9(2):118-126. [Crossref]
• 28. Elbetieha A, Da’as SI. Assessment of antifertility activities of abamectin pesticide in male rats. Ecotoxicol Environ Saf. 2003;55(3):307-313. [Crossref]
• 29. İleritürk M, Doğan T, Kandemir O. Investigation of the effect of berberine with arginase activity and oxidantantioxidant parameters on bortezomib-induced spleen injury in rats. Kocatepe Vet J. 2021;14(1):6-15. [Crossref]
• 30. Ileriturk M, Benzer F, Aksu EH, et al. Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti-inflammatory, and antiapoptotic properties. J Food Biochem. 2021;45(2):e13593. [Crossref]
• 31. Küçükler S, Çomaklı S, Özdemir S, Çağlayan C, Kandemir FM. Hesperidin protects against the chlorpyrifos-induced chronic hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up-regulation of PARP-1/VEGF. Environ Toxicol. 2021;36(8):1600-1617. [Crossref]
• 32. Kumar A, Sasmal D, Sharma N. Mechanism of deltamethrin induced thymic and splenic toxicity in mice and its protection by piperine and curcumin: in vivo study. Drug Chem Toxicol. 2018;41(1):33-41. [Crossref]
• 33. Coşkun P, Benzer F, Kandemir F, Yıldırım S, Küçükler S. Ratlarda kurşun asetat kaynaklı karaciğer hasarı üzerine Chrysin’in etkilerinin araştırılması. Türk Tarım ve Doğa Bilimleri Dergisi. 2021;8(2):250-261. [Crossref]
• 34. Sakat MS, Kılıç K, Akdemir FNE, Yıldırım S, Eser G, Kızıltunç A. The effectiveness of eugenol against cisplatin-induced ototoxicity. Braz J Otorhinolaryngol. 2019;85(6):766-773. [Crossref]
• 35. Özdemir S, Küçükler S, Çomaklı S, Kandemir FM. The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis. Drug Chem Toxicol. 2020;1-10. [Crossref]
• 36. Küçükler S, Özdemir S, Çomaklı S, Kandemir F. Ratlarda izoniazid kaynaklı akciğer hasarına karşı krisinin etkileri. Kocatepe Vet J. 2020;13(2):161-171.
• 37. Temel Y, Küçükler S, Yıldırım S, Çağlayan C, Kandemir FM. Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(3):325-337. [Crossref]
• 38. Benzer F, Kandemir FM, Özkaraca M, Küçükler S, Çağlayan C. Curcumin ameliorates doxorubicin-induced cardiotoxicity by abrogation of inflammation, apoptosis, oxidative DNA damage, and protein oxidation in rats. J Biochem Mol Toxicol. 2018;32(2):e22030. [Crossref]
• 39. Çelik H, Küçükler S, Özdemir S, et al. Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. Neurotoxicology. 2020;80:29-40. [Crossref]
• 40. Kandemir FM, Yıldırım S, Çağlayan C, Küçükler S, Eser G. Protective effects of zingerone on cisplatin-induced nephrotoxicity in female rats. Environ Sci Pollut Res. 2019;26(22):22562-22574. [Crossref]
• 41. Kandemir FM, Yıldırım S, Kucukler S, Caglayan C, Darendelioğlu E, Dortbudak MB. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem Toxicol. 2020;138:111190. [Crossref]
• 42. Thangarajan S, Vedagiri A, Somasundaram S, Sakthimanogaran R, Murugesan M. Neuroprotective effect of morin on lead acetate-induced apoptosis by preventing cytochrome c translocation via regulation of Bax/Bcl-2 ratio. Neurotoxicol Teratol. 2018;66:35-45. [Crossref]
• 43. Aksu EH, Kandemir FM, Küçükler S, Mahamadu A. Improvement in colistin-induced reproductive damage, apoptosis, and autophagy in testes via reducing oxidative stress by chrysin. J Biochem Mol Toxicol. 2018;32(11):e22201. [Crossref]
• 44. Chen YJ, Chen HP, Cheng YJ, et al. The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway. Life Sci. 2013;92(22):1081-1092. [Crossref]
• 45. Kumar A, Sasmal D, Bhaskar A, Mukhopadhyay K, Thakur A, Sharma N. Deltamethrin-induced oxidative stress and mitochondrial caspase- dependent signaling pathways in murine splenocytes. Environ Toxicol. 2016;31(7):808-819. [Crossref]