The Effect of Antioxidants Uses with Aminoglycosides Antibiotics on Serum Creatinine and Urea Levels
Abstract
Aminoglycosides are older-generation antibiotics used to treat infectious diseases like tuberculosis and urinary tract infections. While they improve multidrug resistant tuberculosis treatment success, their nephrotoxicity hinders optimal therapy. This study investigated the concomitant use of aminoglycosides (streptomycin, gentamicin, and kanamycin) and antioxidants to mitigate nephrotoxicity, as measured by serum creatinine and urea levels. Using a retrospective, descriptive analytical design, we analyzed medical records of 32 patients treated with aminoglycoside antibiotics at dr. Wahidin Sudirohusodo Hospital, Makassar, from January 2017 to November 2018. Patients were grouped based on antioxidant treatment: N-acetylcysteine (NAC), N-acetylcysteine and Curcuma (NAC+Cur), vitamin C (Vit C), Curcuma and vitamin C (Cur+Vit C), and a control group (X) receiving no antioxidants. All antioxidant groups showed decreased creatinine and urea levels with streptomycin, except the control group, which exhibited increased levels. With gentamicin, only vitamin C decreased urea. For kanamycin, NAC, NAC+Cur, and Cur+Vit C decreased urea, while NAC+Cur also decreased creatinine. NAC alone and the NAC+Cur combination showed the greatest ability to reduce serum creatinine and urea levels for both streptomycin and kanamycin. These findings suggest that antioxidant supplementation, particularly NAC and NAC+Cur, may play a crucial role in mitigating aminoglycoside-induced nephrotoxicity. Reduced creatinine and urea levels with antioxidant use could translate to improved renal function and potentially better patient outcomes during aminoglycoside therapy. Further research is needed to confirm these findings and explore optimal antioxidant dosing strategies in clinical practice.
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Reeves AZ, Campbell PJ, Sultana R, Malik S, Murray M, Plikaytis BB, et al. Aminoglycoside Cross-Resistance in Mycobacterium tuberculosis Due to Mutations in the 5′ Untranslated Region of whiB7. Antimicrob Agents Chemother. 2013 Apr;57(4):1857–65.
World Health Organization, editor. WHO Treatment Guidelines for Drug-Resistant Tuberculosis OCTOBER 2016 REVISION [Internet]. Oct 2016 Revision. Geneva: World Health Organization; 2016 [cited 2022 Dec 17]. Available from: https://www.who.int/publications/i/item/9789241549639
Purnasari C, Manggau MA, Kasim H. Study of The Dosage And Duration Effect of Aminoglycoside Therapy To Renal Function. Majalah Farmasi dan Farmakologi. 2019 Mar 18;22(3):76–80.
Picard W, Bazin F, Clouzeau B, Bui HN, Soulat M, Guilhon E, et al. Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock. Antimicrob Agents Chemother. 2014 Dec;58(12):7468–74.
Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 2011 Jan 1;79(1):33–45.
Vicente-Vicente L, Casanova AG, Hernández-Sánchez MT, Pescador M, López-Hernández FJ, Morales AI. A systematic meta-analysis on the efficacy of pre-clinically tested nephroprotectants at preventing aminoglycoside nephrotoxicity. Toxicology. 2017 Feb 15;377:14–24.
Wargo KA, Edwards JD. Aminoglycoside-Induced Nephrotoxicity. J Pharm Pract. 2014 Dec 7;27(6):573–7.
Casanova AG, Vicente-Vicente L, Hernández-Sánchez MT, Pescador M, Prieto M, Martínez-Salgado C, et al. Key role of oxidative stress in animal models of aminoglycoside nephrotoxicity revealed by a systematic analysis of the antioxidant-to-nephroprotective correlation. Toxicology. 2017 Jun 15;385:10–7.
Beauduy CE, Winston LG. Chapter 45 Aminoglycosides & Spectinomycin. In: Katzung BG, editor. Basic and Clinical Pharmacology. 14th Edition. McGraw-Hill Education; 2018. p. 826–33.
Ishikawa M, García-Mateo N, Čusak A, López-Hernández I, Fernández-Martínez M, Müller M, et al. Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use. Sci Rep. 2019 Feb 20;9(1):2410.
Jospe-Kaufman M, Siomin L, Fridman M. The relationship between the structure and toxicity of aminoglycoside antibiotics. Bioorg Med Chem Lett. 2020 Jul 1;30(13):127218.
Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J. 2017;16:388–99.
Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. 2018 Jul 3;52(7):751–62.
Vural A, Koçyiğit İ, Şan F, Eroğlu E, Ketenci İ, Ünal A, et al. Long-Term Protective Effect of N-Acetylcysteine against Amikacin-Induced Ototoxicity in End-Stage Renal Disease: A Randomized Trial. Perit Dial Int. 2018 Jan 1;38(1):57–62.
Moreira MA, Nascimento MA, Bozzo TA, Cintra A, da Silva SM, Dalboni MA, et al. Ascorbic acid reduces gentamicin-induced nephrotoxicity in rats through the control of reactive oxygen species. Clinical Nutrition. 2014 Apr 1;33(2):296–301.
Derakhshanfar A, Roshanzamir M, Bidadkosh A. Dose-related protecting effects of vitamin C in gentamicin-induced rat nephrotoxicity: a histopathologic and biochemical study. Comp Clin Path. 2013 May 10;22(3):441–7.
Omotoso DR, Olajumoke JM. Ameliorative Effects of Ascorbic Acid and Allium sativum (Garlic) Ethanol Extract on Renal Parenchyma of Gentamicin-induced Nephropathic Rats. Journal of Complementary and Alternative Medical Research. 2020 May 28;1–8.
Rahmat E, Lee J, Kang Y. Javanese Turmeric (Curcuma xanthorrhiza Roxb.): Ethnobotany, Phytochemistry, Biotechnology, and Pharmacological Activities. Evidence-Based Complementary and Alternative Medicine. 2021 Jun 11;2021:1–15.
Ojha S, Venkataraman B, Kurdi A, Mahgoub E, Sadek B, Rajesh M. Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity. Oxid Med Cell Longev. 2016;2016:1–27.
Ma Q. Role of Nrf2 in Oxidative Stress and Toxicity. Annu Rev Pharmacol Toxicol. 2013 Jan 6;53(1):401–26.
Trujillo J, Molina-Jijón E, Medina-Campos ON, Rodríguez-Muñoz R, Reyes JL, Loredo ML, et al. Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress. Food Funct. 2016;7(1):279–93.
Salim Said SA. A study of hepatoprotective effects of Curcuma Xanthorrhiza and Ipomoea Aquatica on thioacetamide-induced liver cirrhosis in rats (Thesis (Ph.D.). Kuala Lumpur: University of Malaya; 2013.
Kim MB, Kim C, Song Y, Hwang JK. Antihyperglycemic and Anti-Inflammatory Effects of Standardized Curcuma xanthorrhiza Roxb. Extract and Its Active Compound Xanthorrhizol in High-Fat Diet-Induced Obese Mice. Evidence-Based Complementary and Alternative Medicine. 2014;2014:1–10.
Rhee C, Kadri SS, Dekker JP, Danner RL, Chen HC, Fram D, et al. Prevalence of Antibiotic-Resistant Pathogens in Culture-Proven Sepsis and Outcomes Associated With Inadequate and Broad-Spectrum Empiric Antibiotic Use. JAMA Netw Open. 2020 Apr 16;3(4):e202899.
Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: An Overview. Cold Spring Harb Perspect Med. 2016 Jun 1;6(6):a027029.
Wu H, Huang J. Drug-Induced Nephrotoxicity: Pathogenic Mechanisms, Biomarkers and Prevention Strategies. Curr Drug Metab. 2018 Jul 9;19(7):559–67.
DOI: https://doi.org/10.15416/ijcp.2024.13.2.44394
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