Morphofunctional state of rat kidneys under the conditions of cisplatin-induced acute kidney injury and its correction by melatonin
Ye.A. Dudka, T.S. Shchudrova, A.Ye. Petriuk, I.I. Zamorskii
Higher State Educational Establishment of Ukraine “Bukovinian State Medical University”,
Chernivtsi, Ukraine
DOI: https://doi.org/10.15407/fz64.06.077
Abstract
In experiments on laboratory nonlinear white mature rats, the effect of melatonin (5 mg/kg) on the morphofunctional state of kidneys under the conditions of cisplatin-induced acute kidney injury was studied. It was found that single administration of cisplatin at a dose of 6 mg/kg causes necrosis and disseminated degenerative changes of tubular cells with the development of oliguric form of toxic nephropathy, which is accompanied by a decrease in diuresis by 2.9 times, a reduction of glomerular filtration rate by 5 times, an
increase in plasma creatinine level by 2.2 times, a significant proteinuria and decreased tubular reabsorption capacity. It was established that the use of melatonin in the prophylactic-therapeutic regimen demonstrates a cytoprotective effect in relation to the epitheliocytes of the renal tubules, significantly limiting the degree
and prevalence of histopathological changes, and thus preventing the development of oliguria, as evidenced by a significant increase in diuresis by 1.8 times, glomerular filtration rate – by 2,6 times comparing to untreated animals; prevention of retention azotemia, hypokalemia, and significant loss of sodium ions, reducing proteinuria by 1.7 times and activating ammoniagenesis. The research results prove the prospects
of the further studies to investigate the nephroprotective potential of melatonin under the conditions of renal pathology of different genesis.
Keywords:
cisplatin-induced acute kidney injury; melatonin; nephroprotection
References
- Sharman EH, Bondy SC. Melatonin: A safe nutraceutical and clinical agent. Nutraceuticals: Efficacy, Safety and Toxicity. 2016;501-9.
- Pishak VP, Bulyk RYe, Zamorskii II, Tkachuk SS. Pineal gland: pathomorphology, pathological physiology, pharmacology. Chernivtsi; 2012. [Ukrainian].
- Bonnefont-Rousselot D, Collin F. Melatonin: Action as antioxidant and potential applications in human disease and aging. Toxicology. 2010;278(1):55-67.
CrossRef
PubMed
- Reiter R, Rosales-Corral S, Tan D, Jou M, Galano A, Xu B. Melatonin as a mitochondria-targeted antioxidant: one of evolution's best ideas. Cell Mol Life Sci. 2017;74(21):3863-81.
CrossRef
PubMed
- Espino J, Rodriguez A, Pariente J. Melatonin and Oxidative Stress in the Diabetic State: Clinical Implications and Potential Therapeutic Applications. Curr Med Chem. 2018;25.
CrossRef
- Ničković V, Novaković T, Lazarević S, Šulović L, Živković Z, Živković J et al. Pre- vs. post-treatment with melatonin in CCl4-induced liver damage: Oxidative stress inferred from biochemical and pathohistological studies. Life Sci. 2018;202:28-34.
CrossRef
PubMed
- Majidinia M, Sadeghpour A, Mehrzadi S, Reiter R, Khatami N, Yousefi B. Melatonin: A pleiotropic molecule that modulates DNA damage response and repair pathways. J Pineal Res. 2017;63(1):e12416.
CrossRef
PubMed
- Lowes D, Webster N, Murphy M, Galley H. Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis. Br J Anaesth. 2013;110(3):472-80.
CrossRef
PubMed PubMedCentral
- Andersen L, Gögenur I, Rosenberg J, Reiter R. The Safety of Melatonin in Humans. Clin Drug Investig. 2015;36(3):169-75.
CrossRef
PubMed
- Bai X, He T, Gao J, Liu Y, Liu J, Han S et al. Melatonin prevents acute kidney injury in severely burned rats via the activation of SIRT1. Sci Rep. 2016;6(1):32199.
CrossRef
PubMed PubMedCentral
- Elbe H, Vardi N, Esrefoglu M, Ates B, Yologlu S, Taskapan C. Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Hum Exp Toxicol. 2014;34(1):100-13.
CrossRef
PubMed
- Fadda L, Mohamed A, Ali H, Hagar H, Aldossari M. Prophylactic administration of carnosine and melatonin abates the incidence of renal toxicity induced by an over dose of titanium dioxide nanoparticles. J Biochem Mol Toxicol. 2018;32(3):e22040.
CrossRef
PubMed
- Hill N, Fatoba S, Oke J, Hirst J, O'Callaghan C, Lasserson D et al. Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. PLoS One. 2016;11(7):e0158765.
CrossRef
PubMed PubMedCentral
- Hayati F, Hossainzadeh M, Shayanpour S, AbediGheshlaghi Z, Beladi Mousavi SS. Prevention of cisplatin nephrotoxicity. J Nephropharmacol. 2016;5(1):57-60.
PubMed
- Oh G, Kim H, Shen A, Lee S, Khadka D, Pandit A et al. Cisplatin-induced Kidney Dysfunction and Perspectives on Improving Treatment Strategies. Electrolyte Blood Press. 2014;12(2):55.
CrossRef
PubMed PubMedCentral
- Kandhare A, Mukherjee A. Efficacy of Antioxidant Supplements on Prevention and Amelioration of Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Value Health. 2017;20(9):A895.
CrossRef
- Kilic U, Kilic E, Tuzcu Z, Tuzcu M, Ozercan I, Yilmaz O et al. Melatonin suppresses cisplatin-induced nephrotoxicity via activation of Nrf-2/HO-1 pathway. Nutr Metab. 2013;10(1):7.
CrossRef
PubMed PubMedCentral
- Zemła A., Grzegorek I., Dzięgiel P., Jabłońska K. Melatonin Synergizes the Chemotherapeutic Effect of Cisplatin in Ovarian Cancer Cells Independently of MT1 Melatonin Receptors. In Vivo. 2017;31(5):801-9.
PubMed PubMedCentral
- Singh AP, Junemann A, Muthuraman A, Jaggi AS, Singh N, Grover K et al. Animal models of acute renal failure. Pharmacol Reports. 2012;64(1):31-44.
CrossRef
- Kamyshnikov VS. Manual on clinical biochemical studies and laboratory diagnostics. 3rd ed. Moscow; 2009. [Russian].
|