Protective Effects of L-Arginine on Mitochondria of Rat Epididymis in Hyperhomocysteinemia Induced by Prolonged Methionine Load

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Abstract

INTRODUCTION: The study of markers of oxidative stress, metabolites of nitric oxide (II) (NOx) and the balance of carnitine fractions in mitochondria of rat epididymis, permits to evaluate the protective role of L-arginine in experimental hyperhomocysteinemia.

AIM: To study the influence of L-arginine on the parameters of energy metabolism, level of NO metabolites, oxidative modification of proteins and balance of carnitine fractions in mitochondria of the head and tail of rat epididymis in hyperhomocysteinemia.

MATERIALS AND METHODS: In animals of group 1 (n = 8), severe hyperhomocysteinemia (HHcy) was modeled by administration of methionine suspension at a dose of 1.5 g/kg twice daily for 21 days with addition of 1% methionine in drinking water; group 2 rats (n = 8) received suspension base without methionine; animals of group 3 (n = 8) were daily administered L-arginine solution at a dose of 500 mg/kg intragastrically against the background methionine load from day 11 to day 21; group 4 animals (n = 8) were administered L-arginine solution of at a dose of 500 mg/kg for 10 days; group 5 (n = 8) served as a control for group 4 and received drinking water intragastrically. Concentrations of total homocysteine and NOx were determined in serum. In the mitochondrial fraction of the homogenate of epididymis tissues, the level of oxidatively modified proteins (OMP), the concentration of NOx, lactate and carnitine fractions, the activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD), H+-ATPase, succinate dehydrogenase (SDH) were evaluated.

RESULTS: HHcy was accompanied by reduction of the level of NOx in blood serum and mitochondria of epididymis head tissues. In mitochondria of tissues of head and tail of epididymis, a marked reduction of all fractions of carnitine, activity of LDH, H+-ATPase, SDH, increase in the activity of SOD and in the level of OMP were observed. With modeled HHcy, L-arginine reduced the extent of hyperhomocysteinemia, prevented reduction of NOx level in the blood serum and epididymis head and reduced the content of OMP of the epididymis mitochondria.

CONCLUSION: L-arginine introduced in combination with methionine, reduces the extent of severity of hyperhomocysteinemia. The positive effect of L-arginine on increase in the concentration of NOx metabolites in blood serum and mitochondria of epididymis in conditions of methionine load was also confirmed. L-arginine exhibits antioxidant properties, reducing the severity of oxidative stress induced by hyperhomocysteinemia. Differences in the adaptive response to oxidative stress of the mitochondria of the head and tail of epididymis were demonstrated.

About the authors

Valentina I. Zvyagina

Ryazan State Medical University

Email: vizvyagina@yandex.ru
ORCID iD: 0000-0003-2800-5789
SPIN-code: 7553-8641

Cand. Sci. (Biol.), Associate Professor

 
Russian Federation, Ryazan

Konstantin B. Shumaev

The Federal Research Centre ‘Fundamentals of Biotechnology’ of the Russian Academy of Sciences

Email: tomorov@mail.ru
ORCID iD: 0000-0001-8835-5188
SPIN-code: 7765-3295

Dr. Sci. (Biol.)

 
Russian Federation, Moscow

Eduard S. Belskikh

Ryazan State Medical University

Email: ed.bels@yandex.ru
ORCID iD: 0000-0003-1803-0542
SPIN-code: 9350-9360

MD, Cand. Sci. (Med.)

 
Russian Federation, Ryazan

Oleg M. Uryasyev

Ryazan State Medical University

Email: uryasev08@yandex.ru
ORCID iD: 0000-0001-8693-4696
SPIN-code: 7903-4609

MD, Dr. Sci. (Med.), Professor

Russian Federation, Ryazan

Sabina R. Akhmedova

Ryazan State Medical University

Author for correspondence.
Email: danfeyt@mail.ru
ORCID iD: 0000-0002-6437-8120
Russian Federation, Ryazan

Yulia A. Marsyanova

Ryazan State Medical University

Email: yuliyamarsyanova@yahoo.com
ORCID iD: 0000-0003-4948-4504
SPIN-code: 4075-3169

 

 
Russian Federation, Ryazan

Anna M. Shitikova

Ryazan State Medical University

Email: anyakudlaeva@mail.ru
ORCID iD: 0000-0002-4004-9058
SPIN-code: 3416-3961

Cand. Sci. (Biol.), Associate Professor

Russian Federation, Ryazan

Olga N. Suchkova

Ryazan State Medical University

Email: suchkovaon@gmail.com
ORCID iD: 0000-0001-5227-7288
SPIN-code: 2282-3653
Russian Federation, Ryazan

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Supplementary files

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2. Fig. 1. Concentration of NOx, homocysteine and free carnitine in blood serum of study groups of animals, Me [Q1; Q3].

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3. Fig. 2. Comparison of the levels of NO (II) metabolites and lactate of mitochondria in the study models, Me [Q1; Q3].

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4. Fig. 3. Comparison of study parameters of oxidative stress of mitochondria in study models, Me [Q1; Q3].

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5. Fig. 4. Comparison of the activity of mitochondrial enzymes in the study models, Me [Q1; Q3].

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6. Fig. 5. Comparison of the content of L-carnitine in mitochondria of homogenates of the head and tail of epididymis in the study models, Me [Q1; Q3].

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7. Fig. 6. Levels of NO (II) metabolites and carnitine in blood serum of intact animals and with introduction of L-arginine, Me [Q1; Q3].

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8. Fig. 7. Changes of the studied parameters of mitochondria of the head and tail of epididymis with administration of L-arginine, Me [Q1; Q3].

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9. Fig. 8. A scheme of probable mechanisms of reduction of the level of homocysteine with administration of L-arginine.

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Copyright (c) 2022 Zvyagina V.I., Shumaev K.B., Belskikh E.S., Uryasyev O.M., Akhmedova S.R., Marsyanova Y.A., Shitikova A.M., Suchkova O.N.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


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