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.
Keywords
Full Text:
PDFReferences
Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: An Overview. Cold Spring Harb Perspect Med. 2016 Jun 1;6(6):a027029. https://doi.org/10.1101/cshperspect.a027029
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. https://doi.org/10.1128/aac.02191-12
WHO Global TB Programme. WHO Operational Handbook on Tuberculosis. Modul 4: Treatment - drug-resistant tuberculosis treatment, 2022, update. 2022nd ed. World Health Organization, editor. Vol. 4. Geneva: World Health Organization; 2022.
Shibeshi W, Sheth AN, Admasu A, Berha AB, Negash Z, Yimer G. Nephrotoxicity and ototoxic symptoms of injectable second-line anti-tubercular drugs among patients treated for MDR-TB in Ethiopia: a retrospective cohort study. BMC Pharmacol Toxicol. 2019 Dec 23;20(1):31. https://doi.org/10.1186/s40360-019-0313-y
Perumal R, Abdelghani N, Naidu N, Yende-Zuma N, Dawood H, Naidoo K, et al. Risk of Nephrotoxicity in Patients With Drug-Resistant Tuberculosis Treated With Kanamycin/Capreomycin With or Without Concomitant Use of Tenofovir-Containing Antiretroviral Therapy. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2018;78(5):536–42. https://doi.org/ 10.1097/QAI.0000000000001705
Le TA, Hiba T, Chaudhari D, Preston AN, Palowsky ZR, Ahmadzadeh S, et al. Aminoglycoside-Related Nephrotoxicity and Ototoxicity in Clinical Practice: A Review of Pathophysiological Mechanism and Treatment Options. Adv Ther. 2023;40(4):1357–65. https://doi.org/10.1007/s12325-023-02436-x
Jiang M, Karasawa T, Steyger PS. Aminoglycoside-Induced Cochleotoxicity: A Review. Front Cell Neurosci. 2017;11. https://doi.org/10.3389/fncel.2017.00308
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;385:10–7. https://doi.org/10.1016/j.tox.2017.04.015
Paquette F, Bernier-Jean A, Brunette V, Ammann H, Lavergne V, Pichette V, et al. Acute Kidney Injury and Renal Recovery with the Use of Aminoglycosides: A Large Retrospective Study. Nephron. 2015;131(3):153–60. https://doi.org/10.1159/000440867
Purnasari C, Manggau MA, Kasim H. Studi Pengaruh Dosis Dan Lama Penggunaan Terapi Aminoglikosida Terhadap Fungsi Ginjal. Majalah Farmasi dan Farmakologi. 2019;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;58(12):7468–74. https://doi.org/10.1128/aac.03750-14
Caires RA, da Costa e Silva VT, Burdmann EA, Coelho FO, Costalonga EC. Drug-Induced Acute Kidney Injury. In: Critical Care Nephrology. Elsevier; 2019. p. 214-221.e2. https://doi.org/10.1016/B978-0-323-44942-7.00039-X
Rosenberg CR, Fang X, Allison KR. Potentiating aminoglycoside antibiotics to reduce their toxic side effects. PLoS One. 2020;15(9):e0237948. https://doi.org/10.1371/journal.pone.0237948
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;79(1):33–45. https://doi.org/10.1038/ki.2010.337
Kranzer K, Elamin WF, Cox H, Seddon JA, Ford N, Drobniewski F. A systematic review and meta-analysis of the efficacy and safety of N -acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB. Thorax. 2015;70(11):1070–7. https://doi.org/10.1136/thoraxjnl-2015-207245
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;377:14–24. https://doi.org/10.1016/j.tox.2016.12.003
Mahi-Birjand M, Yaghoubi S, Abdollahpour-Alitappeh M, Keshtkaran Z, Bagheri N, Pirouzi A, et al. Protective effects of pharmacological agents against aminoglycoside-induced nephrotoxicity: A systematic review. Expert Opin Drug Saf. 2020;19(2):167–86. https://doi.org/10.1080/14740338.2020.1712357
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;38(1):57–62. https://doi.org/10.3747/pdi.2017.00133
McWilliam SJ, Antoine DJ, Smyth RL, Pirmohamed M. Aminoglycoside-induced nephrotoxicity in children. Pediatric Nephrology. 2017;32(11):2015–25. https://doi.org/10.1007/s00467-016-3533-z
Wargo KA, Edwards JD. Aminoglycoside-Induced Nephrotoxicity. J Pharm Pract. 2014;27(6):573–7. https://doi.org/10.1177/0897190014546836
Beauduy CE, Winston LG. Chapter 45 Aminoglycosides & Spectinomycin. In: Katzung BG, editor. Basic and Clinical Pharmacology 14th Edition. 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;9(1):2410. https://doi.org/10.1038/s41598-019-38634-3
Jospe-Kaufman M, Siomin L, Fridman M. The relationship between the structure and toxicity of aminoglycoside antibiotics. Bioorg Med Chem Lett. 2020;30(13):127218. https://doi.org/10.1016/j.bmcl.2020.127218
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. https://doi.org/10.17179/excli2017-165
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;52(7):751–62. https://doi.org/10.1080/10715762.2018.1468564
Gounden V, Bhatt H, Jialal I. Renal Function Tests. [Updated 2024 Jul 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK507821/
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;33(2):296–301. https://doi.org/10.1016/j.clnu.2013.05.005
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;22(3):441–7. https://doi.org/10.1007/s00580-012-1430-9
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;1–8. https://doi.org/10.9734/jocamr/2020/v9i430146
Rahmat E, Lee J, Kang Y. Javanese Turmeric (Curcuma xanthorrhiza Roxb.): Ethnobotany, Phytochemistry, Biotechnology, and Pharmacological Activities. Evidence-Based Complementary and Alternative Medicine. 2021;2021:1–15. https://doi.org/10.1155/2021/9960813
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. https://doi.org/10.1155/2016/4320374
Ma Q. Role of Nrf2 in Oxidative Stress and Toxicity. Annu Rev Pharmacol Toxicol. 2013;53(1):401–26. https://doi.org/10.1146/annurev-pharmtox-011112-140320
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. https://doi.org/10.1039/C5FO00624D
Salim Said SA. A study of hepatoprotective effects of Curcuma Xanthorrhiza and Ipomoea Aquatica on thioacetamide-induced liver cirrhosis in rats [Thesis (PhD)]. [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. https://doi.org/10.1155/2014/205915
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;3(4):e202899. https://doi.org/10.1001/jamanetworkopen.2020.2899
Sutanto M, Harsini, Reviono, Aphridasari, Eko V. Relationship Between Kanamycin Injection Treatment and Evaluation of Hearing Loss in MDR-TB Patients in Dr. Moewardi Hospital. [cited 2024 Jul 8]; Available from: https://pulmonologi.fk.uns.ac.id/wp-content/uploads/2016/11/Abstrak-full-text-dr.Magda-revisi.pdf
Ramírez-Marroquín OA, Jiménez-Arellanes MA. Hepato-Protective Effect from Natural Compounds, Biological Products and Medicinal Plant Extracts on Antitubercular Drug-Induced Liver Injuries: A Systematic Review. Med Aromat Plants (Los Angel). 2019;08(05). https://doi.org/ 10.35248/2167-0412.19.8.339
Ulya N, Sumarny R, Arozal W, Musridharta E. Analisis Pemberian N-acetylcysteine Dosis Tinggi Terhadap Fungsi Ginjal Pasien yang Didiagnosis Acute Kidney Injury Periode Januari – Desember 2021 di RSPON Jakarta. Syntax Literate ; Jurnal Ilmiah Indonesia. 2024; 9(8):3970–82. https://doi.org/10.36418/syntax-literate.v9i8
Simatupang LD, Susalit E, Wijaya IP. Peran Kombinasi Hidrasi dan N-Acetyl Cysteine terhadap Nefropati akibat Kontras 48 Jam Pasca Percutaneous Coronary Intervention pada Pasien Penyakit Ginjal Kronik Stadium 3. Jurnal Penyakit Dalam Indonesia. 2017;3(3):125. https://doi.org/10.7454/jpdi.v3i3.22
Wu H, Huang J. Drug-Induced Nephrotoxicity: Pathogenic Mechanisms, Biomarkers and Prevention Strategies. Curr Drug Metab. 2018;19(7):559–67. https://doi.org/10.2174/1389200218666171108154419
DOI: https://doi.org/10.15416/ijcp.2024.13.2.44394
Refbacks
- There are currently no refbacks.
Indonesian Journal of Clinical Pharmacy is indexed by
