Rutinin Ratlarda Kolistin Kaynaklı Testis Hasarında Oksidatif DNA Hasarı, NF-κB Aracılı Enflamasyon ve Apoptoz Üzerindeki Koruyucu Etkileri

Yıl 2020, Cilt: 9 Sayı: 2, 83 - 90, 30.12.2020

Selim Çomaklı Mustafa İleritürk Esra Manavoğlu Kirman

https://doi.org/10.46810/tdfd.809231

Öz

Kolistin, gram-negatif bakterilerin neden olduğu enfeksiyonlarda son seçenek olarak tedavi amacıyla kullanılmaktadır. Literatürde kolistinin neden olduğu testis toksisitesi bildirilmiş olmasına rağmen mekanizmasına ilişkin çok az veri bulunmaktadır. Yapılan bu çalışmanın amacı kolistin uygulamasının neden olduğu testis toksisitesinde rutinin (Rut) koruyucu etkilerinin araştırılmasıdır. Bu amaç için 5 adet deneysel grup oluşturuldu; Kontrol, Rut (100 mg/kg/gün), Kolistin (15 mg/kg/gün), Kolistin + Rut (50 mg/kg/gün), Kolistin + Rut (100 mg/kg/gün). Uygulama sonrasında ratların testis dokularında malondialdehit (MDA) ve redükte glutatyon (GSH) seviyeleri tespit edildi. Aynı zamanda testis dokularının histopatolojik incelemesi yapıldı ve 8-hidroksi-2'-deoksiguanozin (8-OHdG), nükleer faktörü kappa B (NF-κB) ve kaspaz 3 aktiviteleri immunohistokimya ile belirlendi. Sonuçlara bakıldığında kolistin uygulamasının rat testis dokularında MDA düzeyini arttırdığı, GSH düzeyini ise azalttığı tespit edilmiştir. Farklı dozlarda Rut uygulaması sonrası ise MDA düzeyinde azalma, GSH düzeyinde ise artış gözlendi. Kolistinin testis dokularında neden olduğu hasar sonucu 8-OHdG, NF-κB ve kaspaz 3 immunpozitifliklerinin arttığı, özellikle Rut (100 mg/kg/gün) uygulamasından sonra bu proteinlerin aktivite düzeylerinin azaldığı belirlendi. Sonuç olarak kolistinin rat testislerinde oksidatif hasar, enflamasyon, DNA hasarı ve apoptoza neden olduğu, Rut uygulamasının kolistin kaynaklı testis hasarında koruyucu etki gösterdiği belirlendi.

Anahtar Kelimeler

Apoptoz, Enflamasyon, Kolistin, Oksidatif stress, 8-OHdG, Testis

Kaynakça

• [1] Hanedan B, Ozkaraca M, Kirbas A, Kandemir FM, Aktas MS, Kilic K, et al. Investigation of the effects of hesperidin and chrysin on renal injury induced by colistin in rats. Biomed Pharmacother. 2018; 108:1607-16.
• [2] Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S, et al. Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol Biol Rep. 2020; 47(3):2023-34.
• [3] Zavascki AP, Goldani LZ, Li J, Nation RL. Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother. 2007; 60(6):1206-15.
• [4] Heidari R, Behnamrad S, Khodami Z, Ommati MM, Azarpira N, Vazin A. The nephroprotective properties of taurine in colistin-treated mice is mediated through the regulation of mitochondrial function and mitigation of oxidative stress. Biomed Pharmacother. 2019; 109:103-11.
• [5] Dai C, Li J, Li J. New insight in colistin induced neurotoxicity with the mitochondrial dysfunction in mice central nervous tissues. Exp Toxicol Pathol. 2013; 65(6):941-8.
• [6] Yu Z, Zhu Y, Qin W, Yin J, Qiu J. Oxidative stress induced by polymyxin E is involved in rapid killing of Paenibacillus polymyxa. Biomed Res Int. 2017; 2017.
• [7] 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.
• [8] Kandemir FM, Caglayan C, Aksu EH, Yildirim S, Kucukler S, Gur C, et al. Protective effect of rutin on mercuric chloride‐induced reproductive damage in male rats. Andrologia. 2020; 52(3):e13524.
• [9] 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(1):e12593.
• [10] Ganeshpurkar A, Saluja AK. The pharmacological potential of rutin. Saudi Pharm J. 2017; 25(2):149-64.
• [11] 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. J Trace Elem Med Biol. 2019; 56:60-8.
• [12] 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. J Trace Elem Med Biol. 2019; 54:69-78.
• [13] Ajiboye T. Colistin sulphate induced neurotoxicity: Studies on cholinergic, monoaminergic, purinergic and oxidative stress biomarkers. Biomed Pharmacother. 2018; 103:1701-7.
• [14] Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966; 16(2):359-64.
• [15] Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968; 25:192-205.
• [16] Dai C, Tang S, Wang Y, Velkov T, Xiao X. Baicalein acts as a nephroprotectant that ameliorates colistin-induced nephrotoxicity by activating the antioxidant defence mechanism of the kidneys and down-regulating the inflammatory response. J Antimicrob Chemother. 2017; 72(9):2562-9.
• [17] Edrees NE, Galal AA, Monaem ARA, Beheiry RR, Metwally MM. Curcumin alleviates colistin-induced nephrotoxicity and neurotoxicity in rats via attenuation of oxidative stress, inflammation and apoptosis. Chem Biol Interact. 2018; 294:56-64.
• [18] Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organization Journal. 2012; 5(1):9-19.
• [19] Yousef JM, Chen G, Hill PA, Nation RL, Li J. Melatonin attenuates colistin-induced nephrotoxicity in rats. Antimicrob Agents Chemother. 2011; 55(9):4044-9.
• [20] Dai C, Zhang D, Gao R, Zhang X, Li J, Li J. In vitro toxicity of colistin on primary chick cortex neurons and its potential mechanism. Environ Toxicol Pharmacol. 2013; 36(2):659-66.
• [21] Dai C, Tang S, Deng S, Zhang S, Zhou Y, Velkov T, et al. Lycopene attenuates colistin-induced nephrotoxicity in mice via activation of the Nrf2/HO-1 pathway. Antimicrob Agents Chemother. 2015; 59(1):579-85.
• [22] Chi X, Bi S, Xu W, Zhang Y, Liang S, Hu S. Oral administration of tea saponins to relive oxidative stress and immune suppression in chickens. Poult Sci. 2017; 96(9):3058-67.
• [23] Zhang Y, Chi X, Wang Z, Bi S, Wang Y, Shi F, et al. Protective effects of Panax notoginseng saponins on PME-Induced nephrotoxicity in mice. Biomed Pharmacother. 2019; 116:108970.
• [24] Jiang G-Z, Li J-C. Protective effects of ginsenoside Rg1 against colistin sulfate-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol. 2014; 34(2):167-72.
• [25] Wang J, Ishfaq M, Xu L, Xia C, Chen C, Li J. METTL3/m6A/miRNA-873-5p Attenuated Oxidative Stress and Apoptosis in Colistin-Induced Kidney Injury by Modulating Keap1/Nrf2 Pathway. Front Pharmacol. 2019; 10:517.
• [26] Hosen MB, Islam MR, Begum F, Kabir Y, Howlader MZH. Oxidative stress induced sperm DNA damage, a possible reason for male infertility. Iran J Reprod Med. 2015; 13(9):525.
• [27] Said TM, Agarwal A, Sharma RK, Thomas Jr AJ, Sikka SC. Impact of sperm morphology on DNA damage caused by oxidative stress induced by β-nicotinamide adenine dinucleotide phosphate. Fertil Steril. 2005; 83(1):95-103.
• [28] Shen H-M, Ong C-N. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radic Biol Med. 2000; 28(4):529-36.
• [29] Özdemir S, Kucukler 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.
• [30] Wong YT, Ruan R, Tay FEH. Relationship between levels of oxidative DNA damage, lipid peroxidation and mitochondrial membrane potential in young and old F344 rats. Free Radic Res. 2006; 40(4):393-402.
• [31] Park J-W, Floyd RA. Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA. Free Radic Biol Med. 1992; 12(4):245-50.
• [32] Kucukler S, Darendelioğlu E, Caglayan C, Ayna A, Yıldırım S, Kandemir FM. Zingerone attenuates vancomycin-induced hepatotoxicity in rats through regulation of oxidative stress, inflammation and apoptosis. Life Sci. 2020:118382.
• [33] Aprioku JS. Pharmacology of free radicals and the impact of reactive oxygen species on the testis. J Reprod Infertil. 2013; 14(4):158.
• [34] 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.
• [35] Shishodia S, Majumdar S, Banerjee S, Aggarwal BB. Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBα kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer Res. 2003; 63(15):4375-83.
• [36] Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science. 1995;267(5203):1456-62.
• [37] Rubin LL. Neuronal cell death: when, why and how. Br Med Bull. 1997; 53(3):617-31.
• [38] Mattson MP, Chan SL. Calcium orchestrates apoptosis. Nat Cell Biol. 2003; 5(12):1041-3.
• [39] Falagas ME, Kasiakou SK. Toxicity of polymyxins: a systematic review of the evidence from old and recent studies. Crit Care. 2006; 10(1):R27.
• [40] Dai C, Li J, Lin W, Li G, Sun M, Wang F, et al. Electrophysiology and ultrastructural changes in mouse sciatic nerve associated with colistin sulfate exposure. Toxicol Mech Methods. 2012; 22(8):592-6.
• [41] Dai C, Xiao X, Zhang Y, Xiang B, Hoyer D, Shen J, et al. Curcumin Attenuates Colistin-Induced Peripheral Neurotoxicity in Mice. ACS Infect Dis. 2020; 6(4):715-24.
• [42] Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S, et al. Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol Biol Rep. 2020; 47(3):2023-34.
• [43] Dai C, Xiong J, Wang Y, Shen J, Velkov T, Xiao X. Nerve Growth Factor Confers Neuroprotection against Colistin-Induced Peripheral Neurotoxicity. ACS Infect Dis. 2020; 6(6):1451-9.
• [44] Wang J, Ishfaq M, Fan Q, Chen C, Li J. 7-Hydroxycoumarin Attenuates Colistin-Induced Kidney Injury in Mice Through the Decreased Level of Histone Deacetylase 1 and the Activation of Nrf2 Signaling Pathway. Front Pharmacol. 2020; 11:1146.
• [45] Yaşar H, Ersoy A, Cimen FK, Mammadov R, Kurt N, Arslan YK. Peripheral neurotoxic effects of cisplatin on rats and treatment with rutin. Adv Clin Exp Med. 2019; 28(11):1537-43.
• [46] Abdelfattah MS, Badr SEA, Lotfy SA, Attia GH, Aref AM, Abdel Moneim AE, et al. Rutin and Selenium Co-administration Reverse 3-Nitropropionic Acid-Induced Neurochemical and Molecular Impairments in a Mouse Model of Huntington's Disease. Neurotox Res. 2020; 37(1):77-92.
• [47] 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. J Trace Elem Med Biol. 2019; 56:60-8.
• [48] Khan F, Pandey P, Upadhyay TK, Jafri A, Jha NK, Mishra R, et al. Anti-Cancerous Effect of Rutin Against HPV-C33A Cervical Cancer Cells via G0/G1 Cell Cycle Arrest and Apoptotic Induction. Endocr Metab Immune Disord Drug Targets. 2020; 20(3):409-18.
• [49] Gao H, Yuan X, Wang Z, Gao Q, Yang J. Profiles and neuroprotective effects of Lycium ruthenicum polyphenols against oxidative stress-induced cytotoxicity in PC12 cells. J Food Biochem. 2020; 44(1):e13112.