Protective Effect of Krill Oil Against Gentamicin Induced Oxidative Stress Mediated Nephrotoxicity in Rats

Yıl 2022, Cilt: 15 Sayı: 1, 38 - 46, 31.03.2022

Yaşar Şahin , Mehmet Eray Alçığır , Ali Şenol , Hüseyin Özden , Hüsamettin Ekici , Ebru Yıldırım , Miyase Çınar

https://doi.org/10.30607/kvj.1051733

Öz

This study aimed to evaluate the protective effect of krill oil against nephrotoxicity caused by gentamicin. Distilled water was given orally to the control and second groups (GI) for seven days while 500 mg/kg krill oil was given to the third (GII), fourth (GIII) groups. In addition, isotonic saline was administered subcutaneously to the control and GIII groups throughout the study, while 80 mg/kg gentamicin was administered to the GI, and GII groups. Alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) peptidase, total cholesterol, urea, and creatinine levels in plasma and, malondialdehyde (MDA) and total antioxidant status (TAS) levels in both plasma and kidney tissue supernatant were evaluated. Histopathological changes in tubules and glomeruli and vascular changes were evaluated by scoring. Urea level and ALT activity were found to be significantly lower in the GII and GIII groups compared to the GI group (p<0.001; p≤0.001). As a result, it was observed that degenerative damage and glomerular changes in the tubule at the histological level mediated by oxidative stress were consistent with the increase in ALT, urea, and MDA levels. In this respect, it is suggested that krill oil can be used as a nephroprotective food supplement to contribute to treatment in cases of toxicity.

Anahtar Kelimeler

Gentamicin, Kidney, Krill oil, Nephrotoxicity, Oxidative stress

Sıçanlarda Gentamisin ile İndüklenmiş Oksidatif Stres Aracılı Nefrotoksisiteye Karşı Krill Yağının Koruyucu Etkisi

Öz

Bu çalışmada, gentamisin'in neden olduğu nefrotoksisiteye karşı kril yağının koruyucu etkisinin değerlendirilmesi amaçlandı. Çalışmada yedi gün boyunca oral yolla kontrol ve ikinci grubuna (GI) distile su verilirken, üçüncü (GII) ve dördüncü (GIII) gruplarına 500mg/kg krill yağı verildi. Ayrıca çalışma boyunca subkutan yolla kontrol ve GIII gruplarına izotonik tuzlu su uygulanırken, GI ve GII gruplarına 80 mg/kg gentamisin uygulandı. Plazma alanin aminotransferaz (ALT) ve gama glutamiltransferaz (GGT), total kolesterol, üre ve kreatinin düzeylerine, hem plazma hem de böbrek doku süpernatından ise malondialdehit (MDA) ve total antioksidan kapasitesi (TAS) düzeylerine değerlendirildi. Histopatolojik olarak tubul ve glomeruluslardaki değişimler ile damarsal değişiklikler skorlanarak değerlendirildi. Üre düzeyi ve ALT aktivitesi GI gruba göre GII ve GIII verilen grupta anlamlı düzeyde düşük bulundu (p<0.001; p≤0.001). Sonuç olarak, oksidatif stres aracılı olarak histolojik düzeyde tubulde dejeneratif hasar ve glomerular değişikliklerin özellikle ALT, üre ve MDA düzeyleri artışıyla uyumlu olduğu görüldü. Bu bakımdan, krill yağı nefroprotektif bir gıda takviyesi olarak toksisite durumlarında tedaviye katkı sağlamak için kullanılabileceği önerilmektedir. 

Anahtar Kelimeler

Böbrek, Gentamisin, Kril yağı, Nefrotoksisite, Oksidatif stres

Kaynakça

• Bartlett PC, Kirk JH, Mather EC. Repeated insemination in Michigan Holstein-Friesian cattle: incidence, descriptive epidemiology and estimated economic impact. Theriogenelogy. 1985; 26: 309–322.
• Acharya C, Thakar H, Vajpeyee SK. A study of oxidative stress in gentamicin induced nephrotoxicity and effect of antioxidant vitamin C in wistar rats. Natl J Physiol Pharm Pharmacol. 2013; 3(1): 14-20.
• Ataman N, Mert H, Yıldırım S, Mert N. The effect of fucoidan on changes of some biochemical parameters in nephrotoxicity induced by gentamicin in rats. Ankara Univ Vet Fak Derg. 2018; 65(1): 9-14.
• Atessahin A, Karahan I, Yilmaz S, Çeribaşi AO, Princi I. The effect of manganese chloride on gentamicin-induced nephrotoxicity in rats. Pharmacol Res. 2003; 48: 637-642.
• Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it?. Pharmacol Res. 2010; 62(3): 179-186.
• Buang Y, Wang YM, Cha JY, Nagao K, Yanagita T. Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid. Nutrition, 2005; 21(7-8): 867-873.
• Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302-310.
• Burri L, Johnsen L. Krill products: an overview of animal studies. Nutrients. 2015; 7(5): 3300-3321.
• Celebi S, Kaya H, Kaya A. Omega-3 yağ asitlerinin insan sağlığı üzerine etkileri. J Agricultural Sci. 2017; 32(2): 105-112.
• Celik OY, Irak K. Protective effect of date extract on rat nephrotoxicity induced by gentamicin, clinical, histological and antioxidant evidences. Cell Mol Biol (Noisy-le-grand). 2018; 64(14): 108-113.
• Cicero AF, Collett A. Krill oil: evidence of a new source of polyunsaturated fatty acids with high bioavailability. Clin Lipidol. 2015; 10: 1-4.
• Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Di Paola R, Britti D, De Sarro A, Pierpaoli S, Caputi A, Masini E, Salvemini D. A role for superoxide in gentamicin-mediated nephropathy in rats. Eur J Pharmacol, 2002; 450(1): 67-76.
• Du XH, Yang CL. Mechanism of gentamicin nephrotoxicity in rats and the protective effect of zinc-induced metallothionein synthesis. Nephrol Dial Transplant. 1994; 9: 135-140.
• Dungca NTP. Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in sprague dawley rats. J Ethnopharmacol. 2016; 184: 18-21.
• Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38(12):1103-1111.
• Fauzi A, Titisari N, Sutarso MV. Gentamicin nephrotoxicity in animal model: study of kidney histopathology and physiological functions. IOP Conf Ser: Earth Environ Sci. 2020; 465: 012005.
• Halsted CH. Dietary supplements and functional foods: 2 sides of a coin?. Am J Clin Nutr. 2003; 77(4): 1001-1007.
• Hayward RS, Harding J, Molloy R, Land L, Longcroft-Neal K, Moore D, Ross JDC. Adverse effects of a single dose of gentamicin in adults: a systematic review. Br J Clin Pharmacol. 2018; 84(2): 223-238.
• Higuera-Ciapara I, Félix-Valenzuela L, Goycoolea FM. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr. 2006; 46(2): 185-196.
• Hung MC, Shibasaki K, Yoshida R, Sato M, Imaizumi K. Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine-vitamin B12 diet. Br J Nutr. 2001; 86(2): 163-171.
• Hur E, Galip A, Camyar A, Ilgun S, Ozisik M, Tuna S, Olukman M, Narli Ozdemir Z, Yildirim Sozmen E, Sen S, Akcicek F, Duman S. The effects of vitamin D on gentamicin-ınduced acute kidney ınjury in experimental rat model. Int J Endocrinol, 2013; 2013: 313528.
• Jiang M, Karasawa T, Steyger PS. Aminoglycoside-induced cochleotoxicity: a review. Front Cell Neurosci. 2017; 11: 308.
• Karakoyun B, Yuksel M, Turan P, Arbak S, Alican I. Halofuginone has a beneficial effect on gentamicin-induced acute nephrotoxicity in rats. Drug Chem Toxicol. 2009; 32(4): 312-318.
• Khan SA, Priyamvada S, Farooq N, Khan S, Khan MW, Yusufi AN. Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Pharmacol Res. 2009; 59(4): 254-262.
• Knight JA. Free radicals: their history and current status in aging and disease. Ann Clin Lab Sci. 1998; 28: 331-346.
• Kwantes JM, Grundmann O. A brief review of krill oil history, research, and the commercial market. J Diet Suppl. 2015; 12(1): 23-35.
• Leslie MA, Cohen DJ, Liddle DM, Robinson LE, Ma DW. A review of the effect of omega-3 polyunsaturated fatty acids on blood triacylglycerol levels in normolipidemic and borderline hyperlipidemic individuals. Lipids Health Dis, 2015; 14: 53.
• Li J, Li QX, Xie XF, Ao Y, Tie CR, Song RJ. Differential roles of dihydropyridine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin-induced renal tubular toxicity in rats. Eur J Pharmacol. 2009; 620(1-3): 97-104.
• Luna LG. Manual of histologic staining methods of the armed forces ınstitute of pathology. 3rd Ed., McGraw-Hill, New York, USA. 1968.
• Matsushita T, Kusakabe Y, Kitamura A, Okada S, Murase K. Protective effect of Hydrogen-rich water aganist gentamicin-induced nephrotoxicity in rats using blood oxygenation level-dependent MR imaging. Mang Reson Med Sci. 2011; 10(3): 169-176.
• Morales AI, Detaille D, Prieto M, Puente A, Briones E, Arévalo M, Leverve X, López-Novoa JM, El-Mir MY. Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int. 2010; 77(10): 861-869.
• Özden H, Gömeç M, Şahin Y, Karaca G, Bulut H, Kilitci A. Protective effect of resveratrol on the kidney in rats under immunosuppression with tacrolimus. J Surg Med. 2021; 5(2): 144-148.
• Papich MG, Riviere JE. Aminoglycoside antibiotics, In: Veterinary Pharmacology and Therapeutics, Ed; Riviere JE, Papich MG, 10th Ed., John Wiley and Sons, Hoboken, USA. 2018 pp; 877-902.
• Pashkow FJ, Watumull DG, Campbell CL. Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol. 2008;101(10): 58-68.
• Peyrou M, Hanna PE, Cribb AE. Cisplatin, gentamicin, and p-aminophenol induce markers of endoplasmic reticulum stress in the rat kidneys. Toxicol Sci. 2007; 99(1): 346-53.
• Quiros Y, Vicente L, Morales AI, López-Novoa JM, López-Hernández FJ. An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicol Sci. 2011; 119(2): 245-256.
• Ramasamy A, Jothivel N, Das S, Swapna A, Albert AP, Barnwal P, Babu D. Evaluation of the protective role of glycine max seed extract (soybean oil) in drug-induced nephrotoxicity in experimental rats. J Diet Suppl. 2017; 15(5): 583-595.
• Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: current knowledge and future perspectives. Excli J. 2017; 24(16): 388-399.
• Regec AL, Trump BF, Trifilis AL. Effect of gentamicin on the lysosomal system of cultured human proximal tubular cells: endocytotic activity, lysosomal pH and membrane fragility. Biochem Pharmacol. 1989; 38(15): 2527-2534.
• Sahnoun Z, Jamoussi K, Zeghal KM. Free radicals and antioxidants: human physiology, pathology and therapeutic aspects. Therapie. 1997; 52(4): 251-270.
• Said MM. The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Fundam Clin Pharmacol. 2011; 25(6): 708-716. Sandhya P, Varalakshmi P. Effect of lipoic acid administration on gentamicin-induced lipid peroxidation in rats. J Appl Toxicol. 1997; 17(6): 405-408.
• Schneider H, Braun A, Fullekrug J, Stremmel W, Ehehalt R. Lipid based therapy for ulcerative colitis-modulation of intestinal mucus membrane phospholipids as a tool to influence inflammation. Int J Mol Sci. 2010; 11(10): 4149-4164.
• Tavafi M, Ahmadvand H. Effect of rosmarinic acid on inhibition of gentamicin induced nephrotoxicity in rats. Tissue Cell. 2011; 43(6): 392-397.
• Tripathi DN, Jena GB. Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress, DNA damage and early hepatocarcinogenesis in rat: role of Nrf2, p53, p38 and phase-II enzymes. Mutat Res. 2010; 696(1): 69-80.
• Ulutaş B, Kıral F, Bırıncıoğlu S. Unable to protect gentamicin-induced nephrotoxicity with allopurinol in rats. Ankara Üniv Vet Fak Derg.2006; 53(1): 65-68.
• Vargo KA, Edwards JD. Aminoglycoside-induced nephrotoxicity. J Pharm Pract. 2014; 27(6): 573-577.
• Walker PD, Barri Y, Shah SV. Oxidant mechanisms in gentamicin nephrotoxicity. Ren Fail. 1999; 21(3-4): 433-442.
• Winther B, Hoem N, Berge K, Reubsaet L. Elucidation of phosphatidylcholine composition in krill oil extracted from Euphausia superba. Lipids. 2011; 46(1): 25-36.
• Yeral I, Sayan CD, Karaca G, Simsek Y, Sagsoz N, Ozkan ZS, Atasoy P, Sahin Y, Neselioglu S, Erel O. What is the protective effect of krill oil on rat ovary against ischemia-reperfusion injury?. J Obstet Gynaecol Res. 2019; 45(3): 592-599.