MELATONIN EFFECT ON THE STATE OF OXIDANT AND ANTIOXIDANT SYSTEMS AND HYDROGEN SULFIDE LEVEL IN THE BLOOD OF RATS UNDER CONDITIONS OF EXPERIMENTAL NEPHROPATHY

Authors

  • I. O. Kolianyk BUKOVYNA STATE MEDICAL UNIVERSITY, CHERNIVTSI
  • I. V. Gerush BUKOVYNA STATE MEDICAL UNIVERSITY, CHERNIVTSI
  • N. P. Grygorieva BUKOVYNA STATE MEDICAL UNIVERSITY, CHERNIVTSI

DOI:

https://doi.org/10.11603/mcch.2410-681X.2021.i1.12106

Keywords:

nephropathy, folic acid, antioxidant system, melatonin, hydrogen sulfide

Abstract

Introduction. Oxidative stress is involved into pathogenesis of various diseases including acute and chronic kidney damage and is characterized by an increased intracellular level of oxygen active forms. It plays an important role in the development of nephropathy and is a potential target for therapeutic intervention. In recent years, the study of Н2S role in maintenance of oxidation-reduction (redox) homeostasis and its effect on the activity of antioxidant protection has become relevant. Melatonin is one of the most common antioxidants. It is able to bind free radicals and stimulate the activity of antioxidant enzymes. Though, the mechanisms of its effect on Н2S content and antioxidant system of blood with nephropathy remain uncertain.

The aim of the study – to find out melatonin effect on blood biochemical values, the oxidative-antioxidative system and hydrogen sulfide level in the blood of rats under conditions of experimental nephropathy.

Research Methods. The experiment was conducted on 127 non-linear male rats with 0.16–0.18 kg of the body weight. Experimental nephropathy was simulated by means of a single injection of folic acid into the peritoneum in the dose of 250 mg/kg of the body weight. Melatonin was introduced into the stomach during 3 and 7 days after nephropathy simulation in the dose of 10 mg/kg. The following values were determined in the blood plasma: urea, creatinine, TBA-active products, carbonyl derivatives of the neutral (OMP370) and alkaline character (OMP430), ceruloplasmin, SH-groups and Н2S. The activity of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) was determined in the hemolysate of erythrocytes.

Results and Discussion. Under conditions of nephropathy the concentration of urea, creatinine, TBA-active products, OMP370, OMP430, ceruloplasmin increased, and the activity of such antioxidant enzymes as catalase, SOD, GPx, GST, the content of SH-groups and Н2S decreased. These changes are indicative of functional disorders of the kidneys, development of oxidative stress and exhaustion of the antioxidant protection. Administration of melatonin during 7 days promotes normalization of the values characterizing the kidney functional state, blood oxidant state, and produces a positive effect on the activity of catalase, GPx, GST, ceruloplasmin level and the content of SH-groups and Н2S.

Conclusion. Administration of exogenous melatonin in the dose of 10 mg/kg during 3 and 7 days reduces the signs of nephrotic syndrome and free radical oxidation of biomolecules, normalizes antioxidative system and Н2S content, which might be associated with its ability to neutralize free radicals and activate antioxidant enzymes.

References

Hong, Y.A., & Park, C.W. (2021). Catalytic anti­oxidants in the Kidney. Antioxidants (Basel), 10 (1), 130.

Irazabal, M. & Torres, V. (2020). Reactive oxygen species and redox signaling in chronic kidney disease. Cells, 9 (6), 1342.

Kuhn, V., Diederich, L., Stevenson Keller IV, T.C., Kramer, C.M., Lückstädt, W., Panknin, Ch., … Cortese-Krott, M.M. (2017). Red blood cell function and dys­function: Redox regulation, nitric oxide metabolism, anemiaegulation, nitric oxide metabolism, anemia. Antioxidants & Redox Signaling, 718-742.

Mohanty, J., Nagababu, E., & Rifkind, J. (2014). Red blood cell oxidative stress impairs oxygen delivery and induces red blood cell aging. Frontiers in Physiology, 5, 84.

Xiao, Q., Ying, J., Xiang, L., & Zhang, C. (2018). The biologic effect of hydrogen sulfide and its function in various diseases. Medicine, 97 (44), e13065.

Corsello, T., Komaravelli, N., & Casola, A., (2018). Role of hydrogen sulfide in NRF2- and sirtuin-dependent maintenance of cellular redox balance. Antioxidants, 7 (10), 129.

Banerjee, A., Chattopadhyay, A., Pal, P. & Ban­dyopadhyay, D. (2020). Melatonin is a potential thera­peutic molecule for oxidative stress induced red blood cell (RBC) injury: A review. Melatonin Research, 3, 1-31.

Gupta, A., Puri, V., Sharma, R. & Puri, S. (2012). Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state. Experimental and Toxicologic Pathology, 64 (3), 225-232.

Nazarenko, O.A., Serheieva, T.A., & Soldatkin, O.P. (2009). Kreatynin ta metody yoho vyznachennia [Creatinine and methods for its determination]. Biotekhnolohiia – Biotechnology, 2, 107-116 [in Ukrainian].

Kamyshnikov, V.S. (2000). Spravochnik po kliniko-biohimicheskoy laboratornoy diagnostike (2-e izd.) [Handbook of clinical and biochemical laboratory diagnostics (2 ed.)]. Minsk [in Russian].

Meshchishen, I.F. (1998) Metod vyznachennia okysno-modyfikovanykh bilkiv plazmy (syrovatky) krovi [Method of determination of oxidative modifiers of plasma proteins (serum)]. Bukovynskyi medychnyi vіsnyk – Bu­kovyna Medical Bulletin, 2 (1), 156-158 [in Ukrainian]

Kolb, V.G., & Kamyshnikov, V.S. (1982). Spravochnik po klinicheskoy khimii [Reference book on Clinical Chemistry]. Minsk [in Russian].

Meshchishen, I. F., & Grigoyeva, N.P. (2002). Metod kilkisnoho vyznachennia HS-hrup u krovi [The method of confirmation of the HS group in blood]. Buko­vynskyi medychnyi vіsnyk – Bukovyna Medical Bulletin, 6, 190-192 [in Ukrainian].

Dombkowski, R.A., Russell, M.J., & Olson, K.R. (2004). Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout. American Journal of physiology. Regulatory, Integrative and Comparative Physiology, 286, 678-685.

Chumakov, V.N., & Osinskaya, L.F. (1979). Kolichestvennyy metod opredeleniya Cu, Zn-zavisimoy superoksiddismutazy v biologicheskom materiale [A quantitative method for the determination of Cu, Zn-dependent superoxide dismutase in biological material]. Vopr. med. khimii – Issues of Medical Chemistry, 5, 716-721 [in Russian].

Korolyuk, M.A., Mayorova, L., & Tokarev, V.E. (1988). Metod opredeleniya aktivnosti katalazy [Method for determination of catalase activity]. Laboratornoe delo – Laboratory Business, 1, 16-19 [in Russian].

Vlasova, S.N., Shabunina, E.I., & Perslegina, I.A. (1990). Aktivnost glutationzavisimykh enzimov eritrotsitov pri khronicheskikh zabolevaniyakh pecheni u detey [The activity of glutathione-dependent erythrocyte enzymes in children with chronic liver diseases]. Laboratornoe delo – Laboratory Business, 8, 19-22 [in Russian].

Gerush, I. V., & Meshchishen, I. F. (1998). Stan hlutationovoi systemy krovi za umov eksperymentalnoho vyrazkovoho urazhennia hastroduodenalnoi zony ta dii nastoiky ekhinatsei purpurovoi [The state of the glutathione blood system under the conditions of experimental ulcerative lesions of the gastroduodenal zone and the action of tincture of Echinacea purpurea]. Visnyk problem biol. ta medytsyny – Bulletin of Problems of Biology and Medicine, 7, 10-15 [in Ukrainian].

Habig, W.H., Pabs, M. J., & Fleischner, G. (1974). The identity of glutathione S-transferase B with ligandin, a major binding protein of liver. Proceedings of the National Academy of Sciences, 71 (10), 3879-3882.

Zhou, T., Prather, E., Garrison, D. & Zuo, L., (2018). Interplay between ROS and antioxidants during ischemia-reperfusion injuries in cardiac and skeletal muscle. In­ternational Journal of Molecular Sciences, 19 (2), 417.

Nandi, A., Yan, L., Jana, C. & Das, N., (2019). Role of catalase in oxidative stress- and age-associated degenerative diseases. Oxidative Medicine and Cellular Longevity, 1-19.

Kaur, M., & Jindal, R. (2017). Oxidative stress response in liver, kidney and gills of ctenopharyngodon idellus(cuvier & valenciennes) exposed to chlorpyrifos. MOJ Biology and Medicine, 1 (4), 103-112.

Luhinich, N.M., & Gerush, I.V. (2019). Vplyv vvedennia melatoninu na stan hlutationovoi systemy i riven hidrohen sulfidu u krovi shchuriv pry aloksanovomu tsukrovomu diabeti [Influence of melatonin introduction on the state of glutathione system and the level of hydrogen sulfide in blood of rats with alloxan induced diabetes mellitus]. Ukrainskyi biofarmatsevtychnyi zhurnal – Ukrainian Biopharmaceutical Journal, 3 (60), 51-56 [in Ukrainian].

Zhao, R., Jiang, S., Zhang, L., & Yu, Z. (2019). Mitochondrial electron transport chain, ROS generation and uncoupling (Review). International Journal of Mo­lecular Medicine, 44, 3-15.

Kurhaluk, N., Tkachenko, H., Lukash, O., Win­klewski, P. & Wszedybyl-Winklewska, M., (2020). Mela­tonin maintains the function of the blood redox system at combined ethanol-induced toxicity and sub­clinical in­flammation in mice. Sleep and Breathing.

Zinchuk, V.V., & Firago, M.Е. (2017). Uchastie melatonina v regulyatsii kislorodtransportnoy funktsii krovi pri okislitelnom stresse, vyzvannom vvedeniem lipo­polisaharida [Participation of melatonin in regulation of blood oxygen-transport function in oxidative stress indu­ced by injection of lipopolisaccaride]. Biomeditsinskaya khimiya – Biomedical Chemistry, 63 (6), 520-526 [in Russian].

Reiter, R.J., Tan, D.X., Rosales-Corral, S., Galano, A., Zhou, X.J. & Xu, B. (2018). Mitochondria: Central organelles for melatonin's antioxidant and anti-aging actions. Molecules, 23, 509.

Published

2021-05-22

How to Cite

Kolianyk, I. O., Gerush, I. V., & Grygorieva, N. P. (2021). MELATONIN EFFECT ON THE STATE OF OXIDANT AND ANTIOXIDANT SYSTEMS AND HYDROGEN SULFIDE LEVEL IN THE BLOOD OF RATS UNDER CONDITIONS OF EXPERIMENTAL NEPHROPATHY . Medical and Clinical Chemistry, (1), 37–44. https://doi.org/10.11603/mcch.2410-681X.2021.i1.12106

Issue

Section

ORIGINAL INVESTIGATIONS