Review of Treatments with Gentamicin-Induced Nephrotoxicity Prevention Potential

Yıl 2023, Cilt: 14 Sayı: 3, 425 - 437, 29.12.2023

Murat Çelebi , Çağla Çelebi , Elif Aksöz

https://doi.org/10.22312/sdusbed.1176151

Öz

Aminoglycosides are among the antibiotics frequently used worldwide due to their low cost, high efficacy, and relatively low bacterial resistance compared to other antibiotics. Despite their widespread use and positive effects, the possibility of accumulating in the renal proximal tubule epithelial cells and causing toxicity limits the comfortable use of these drugs. Although many pharmacological agents have been tried in experimental animals in the hope of being protective against nephrotoxicity that may occur due to aminoglycosides, no nephroprotectant agent that is used routinely has been found yet. Gentamicin has been used as a prototype of aminoglycosides to induce nephrotoxicity in most studies. Antioxidant indices, inflammatory responses, and apoptotic markers were evaluated to assess possible protective efficacy. Natural products, vitamins and minerals, hormones, and many conventional drugs have shown potential effects to prevent nephrotoxicity. In addition, it is seen that the results may vary not only according to the agent used but also the method and duration of administration. Although there are many studies on the subject, it is clear that more research is needed to obtain clear results. In this study, preclinical studies conducted in rodents over the last ten years using gentamicin, an aminoglycoside with the potential to cause nephrotoxicity, were reviewed. In studies on this subject, agents used for treatment and protection were grouped as natural products, minerals and vitamins, hormones, chemical agents and conventional drugs, and it was tried to show how wide a spectrum the agents used were. By providing information about the parameters used in the evaluation in each study, it is aimed to contribute to standardization so that studies can be compared in future studies.

Anahtar Kelimeler

Aminoglycoside, gentamicin, nephrotoxicity, oxidative stress

Gentamisine Bağlı Nefrotoksisiteyi Önleme Potansiyeli Olan Tedavilerin Gözden Geçirilmesi

Öz

Aminoglikozitler, düşük maliyetleri, yüksek etkililikleri ve diğer antibiyotiklere kıyasla nispeten düşük bakteri direncine sahip olmaları nedeniyle dünya çapında sıklıkla kullanılan antibiyotikler arasındadır. Yaygın kullanımlarına ve olumlu etkilerine karşın böbrek proksimal tübülüs epitel hücrelerinde birikerek toksisite gelişimine neden olabilme ihtimalleri bu ilaçların rahatça kullanımını sınırlamaktadır. Aminoglikozitlere bağlı oluşabilecek nefrotoksisiteye karşı koruyucu olması ümidiyle deney hayvanlarında birçok farmakolojik ajan denenmiş olmasına rağmen hali hazırda rutin olarak kullanılan bir nefroprotektan ajan bulunamamıştır. Çalışmaların çoğunda nefrotoksisite oluşturmak için aminoglikozitlerin prototipi olarak gentamisin kullanılmıştır. Muhtemel koruyucu etkinliği değerlendirmek için antioksidan indeksler, inflamatuar yanıtlar ve apoptotik belirteçler değerlendirilmiştir. Doğal ürünler, vitamin ve mineraller, hormonlar ve birçok konvansiyonel ilaç nefrotoksisiteyi önlemek için potansiyel etkiler göstermiştir. Ayrıca, sadece kullanılan ajan değil uygulama yolu ve süresine göre de sonuçların değişebildiği görülmektedir. Konuyla ilgili çok sayıda çalışma olmasına rağmen, net sonuçlar elde etmek için daha fazla araştırma yapılması gerekliliği açıktır. Bu çalışmada, nefrotoksisite oluşturma potansiyeli taşıyan aminoglikozitlerden gentamisin kullanılarak kemirgenler üzerinde son on yılda yapılan klinik öncesi araştırmalar gözden geçirilmiştir. Bu konuda yapılan çalışmalarda tedavi ve koruma amacı ile kullanılan ajanlar, doğal ürünler, mineral ve vitaminler, hormonlar, kimyasal ajanlar ve konvansiyonel ilaçlar olarak gruplandırılmış ve kullanılan ajanların ne kadar geniş bir spektrumda olduğu gösterilmeye çalışılmıştır. Her bir çalışmada değerlendirmede kullanılan parametreler konusunda bilgi verilerek ileride yapılacak araştırmalarda çalışmaların karşılaştırılabilir olması için standardizasyona katkıda bulunmak amaçlanmıştır.

Anahtar Kelimeler

Aminoglikozit, gentamisin, nefrotoksisite, oksidatif stres

Destekleyen Kurum

Balıkesir Üniversitesi

Kaynakça

• [1] Huth ME, Ricci AJ, Cheng AG. Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection. Int. J. Otolaryngol. 2011; 2011:937861. https://doi.org/10.1155/2011/937861
• [2] Hong H, Dooley KE, Starbird LE. ve ark. Adverse outcome pathway for aminoglycoside ototoxicity in drug-resistant tuberculosis treatment. Archives of Toxicology. 2019;93(5):1385–1399. https://doi.org/10.1007/s00204-019-02407-8
• [3] Lopez-Novoa JM, Quiros Y, Vicente L. ve ark. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney International. 2011;79(1):33–45. https://doi.org/https://doi.org/10.1038/ki.2010.337
• [4] Begg EJ ve Barclay ML. Aminoglycosides-50 years on. Br. J. Clin. Pharmac. 1995;39(6):597–603.
• [5] Nabavi SF, Nabavi SM, Moghaddam AH. ve ark. Protective effects of Allium paradoxum against gentamicin-induced nephrotoxicity in mice. Food & function. 2012;3(1):28-29.
• [6] Polat A, Parlakpinar H, Tasdemir S. ve ark. Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats. Acta Histochemica, 2006;108(5):365–371. https://doi.org/https://doi.org/10.1016/j.acthis.2006.06.005
• [7] Karahan İ, Ateşşahin A, Yılmaz S. ve ark. Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxicology. 2005;215(3):198–204. https://doi.org/https://doi.org/10.1016/j.tox.2005.07.007
• [8] Winkler C, Wirleitner B, Schroecksnadel K. ve ark. In vitro effects of beet root juice on stimulated and unstimulated peripheral blood mononuclear cells. Am. J. Biochem. Biotechnol. 2005;1(4):180-185.
• [9] El Gamal AA, AlSaid MS, Raish M. ve ark. Beetroot (Beta vulgaris L.) Extract Ameliorates Gentamicin-Induced Nephrotoxicity Associated Oxidative Stress, Inflammation, and Apoptosis in Rodent Model. Mediators of Inflammation. 2014;2014:983952. https://doi.org/10.1155/2014/983952
• [10] Parlakpinar H, Tasdemir S, Polat A. ve ark. Protective role of caffeic acid phenethyl ester (cape) on gentamicin-induced acute renal toxicity in rats. Toxicology. 2005;207(2):169–177. https://doi.org/https://doi.org/10.1016/j.tox.2004.08.024
• [11] Kumaravelu P, Dakshinamoorthy DP, Subramaniam S, Devaraj H, Devaraj NS. Effect of eugenol on drug-metabolizing enzymes of carbon tetrachloride-intoxicated rat liver. Biochemical Pharmacology. 1995;49(11):1703–1707. https://doi.org/https://doi.org/10.1016/0006-2952(95)00083-C
• [12] Nagababu E, Lakshmaiah N. Inhibition of Microsomal Lipid Peroxidation and Monooxygenase Activities by Eugenol. Free Radical Research. 1994;20(4):253–266. https://doi.org/10.3109/10715769409147521
• [13] 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. https://doi.org/10.1111/j.1472-8206.2010.00900.x
• [14] El-Zawahry BH ve Abu El Kheir EM. The Protective Effect of Curcumin Against Gentamicin-Induced Renal Dysfunction and Oxidative Stress in Male Albino Rats. The Egyptian Journal of Hospital Medicine. 2007;29(1):546–556. https://doi.org/10.21608/ejhm.2007.17699.
• [15] Khaksari M, Esmaili S, Abedloo, R. ve ark. Palmatine ameliorates nephrotoxicity and hepatotoxicity induced by gentamicin in rats. Archives of Physiology and Biochemistry. 2021;127(3):273-278.
• [16] Babaeenezhad E, Nouryazdan N, Nasri M. ve ark. Cinnamic acid ameliorate gentamicin-induced liver dysfunctions and nephrotoxicity in rats through induction of antioxidant activities. Heliyon. 2021;7(7):e07465.
• [17] Jafarey M, Changızı Ashtıyanı S, Najafı H. Calcium Dobesilate for Prevention of Gentamicin-Induced Nephrotoxicity in Rats. Iranıan Journal of KIidney Disease (IJKD) 2014;8(1):46–52. https://www.sid.ir/en/Journal/ViewPaper.aspx?ID=357722
• [18] Randjelovic P, Veljkovic S, Stojiljkovic N. Protective effect of selenium on gentamicin-induced oxidative stress and nephrotoxicity in rats. Drug and Chemical Toxicology. 2012;35(2):141–148. https://doi.org/10.3109/01480545.2011.589446
• [19] Stojiljkovic N, Stoiljkovic M, Randjelovic P, Veljkovic S, Mihailovic D. Cytoprotective effect of vitamin C against gentamicin-induced acute kidney injury in rats. Experimental and Toxicologic Pathology. 2012;64(1-2):69-74.
• [20] Ince S, Kucukkurt I, Demirel H. ve ark. Boron, a trace mineral, alleviates gentamicin-induced nephrotoxicity in rats. Biological Trace Element Research. 2020;195(2):515-524.
• [21] Lee IC, Kim SH, Lee SM. Melatonin attenuates gentamicin-induced nephrotoxicity and oxidative stress in rats. Archives of toxicology. 2012;86(10):1527-1536.
• [22] Kolgazi M, Arbak S, Alican I. The Effect Of Α-Melanocyte Stimulating Hormone On Gentamicin-İnduced Acute Nephrotoxicity in Rats. Journal of Applied Toxicology. 2007;27(2):183–188. https://doi.org/https://doi.org/10.1002/jat.1191.
• [23] Elsakka G, Elsisi M, Mansour M. ve ark. Androgen/androgen receptor affects gentamicin-induced nephrotoxicity through regulation of megalin expression. Life Sciences. 2020;251:117628.
• [24] Dam VP, Scott JL, Ross A, Kinobe RT. Inhibition of cystathionine gamma-lyase and the biosynthesis of endogenous hydrogen sulphide ameliorates gentamicin-induced nephrotoxicity. European Journal of Pharmacology, 2012;685(1):165–173. https://doi.org/https://doi.org/10.1016/j.ejphar.2012.04.030
• [25] Otunctemur A, Ozbek E, Dursun M. ve ark. Protective effect of hydrogen sulfide on gentamicin-induced renal injury. Renal failure. 2014;36(6):925-931.
• [26] Kasap B, Türkmen M, Kiray M. ve ark. Effects of pentoxifylline on gentamicin-induced nephrotoxicity. Renal Failure. 2013;35(10):1376–1381. https://doi.org/10.3109/0886022X.2013.828359
• [27] Özbek E, Cekmen M, İlbey YO, Simsek A, Polat EC, Somay A. Atorvastatin Prevents Gentamicin-Induced Renal Damage in Rats through the Inhibition of p38-MAPK and NF-kB Pathways. Renal Failure. 2009;31(5):382–392. https://doi.org/10.1080/08860220902835863
• [28] Patil AN, Arora T, Desai A, Tripathi CD. Comparison of the species-sensitive effects of different dosages of calcium and verapamil on gentamicin-induced nephrotoxicity in rats and rabbits. Toxicology International. 2014;21(3):225–231. https://doi.org/10.4103/0971-6580.155320
• [29] Dhanarajan R, Abraham P, Isaac B. Protective Effect of Ebselen, a Selenoorganic Drug, against Gentamicin-Induced Renal Damage in Rats. Basic & Clinical Pharmacology & Toxicology. 2006;99(3):267–272. https://doi.org/https://doi.org/10.1111/j.1742-7843.2006.pto_474.x
• [30] Kobori H, Mori H, Masaki T. ve ark. Angiotensin II Blockade and Renal Protection. Current Pharmaceutical Design. 2013;19(17):3033–3042.
• [31] Heeba GH. Angiotensin II Receptor Blocker, Losartan, Ameliorates Gentamicin-Induced Oxidative Stress and Nephrotoxicity in Rats. Pharmacology. 2011;87(3–4):232–240. https://doi.org/10.1159/000325457
• [32] Mahmoud M, Abd El-Ghafar A, Alzoghaibi A. ve ark. Agomelatine prevents gentamicin nephrotoxicity by attenuating oxidative stress and TLR-4 signaling, and upregulating PPARγ and SIRT1. Life Sciences. 2021;278:119600.
• [33] Abd-Eldayem M, Dahpy A, Badary M. ve ark. Celecoxib has preventive and therapeutic benefits against nephrotoxicity caused by gentamicin in mice. Drug Research. 2022;72(05):259-267.
• [34] Abdelrahman S. Protective effect of apocynin against gentamicin-induced nephrotoxicity in rats. Human & Experimental Toxicology. 2018;37(1):27-37.
• [35] Vicente-Vicente L, Casanova G, Hernández-Sánchez T. ve ark. A systematic meta-analysis on the efficacy of pre-clinically tested nephroprotectants at preventing aminoglycoside nephrotoxicity. Toxicology. 2017;377:14-24.