THE COMBINED USE OF PROPARGYLGLYCINE AND L-CYSTEINE PREVENTS OXIDATIVE AND NITROSATIVE STRESS IN CARDIAC TISSUES IN FOCAL CEREBRAL ISCHEMIA-REPERFUSION
N.O. Dorofeeva, Yu.P. Korkach, P.R. Sharipov, V.F. Sagach
O.O. Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz67.03.003
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Abstract
Cerebral ischemia is a neurogenerative disoder that leads to
partial or general paralysis and subsequent disability. The
development of oxidative-nitrosative stress on the background
of insufficient production of nitric oxide (NO) and hydrogen
sulfide (H2S) are the main reasons behind the pathogenesis of
focal ischemia-reperfusion and cerebrocardial syndrome. We
studied the combined use of propargylglycine and L-cysteine
as drugs that prevent oxidative and nitrosative stress and are
activators of gasotransmitters - NO and H2S in the heart tissues
of rats with focal ischemia. It was shown that focal ischemiareperfusion was accompanied by a significant increase in the
heart of rats calcium-independent inducible synthesis of NO
(iNOS) and an increase in markers of oxidative stress (superoxide anion radical, hydroxyl radical, diene conjugates)
NO-synthase (cNOS). This caused disruption of nitric oxide
synthesis due to the uncoupling state of cNOS in the rat heart.
The use of a combination of DL-proparlgylglycine (11.31 mg/
kg) and L-cysteine (112.1 mg / kg) 40 min before the modeling
of focal ischemia significantly reduced the activity of iNOS and
the content of markers of oxidative metabolism in the heart of
adult rats and increased the constitutive synthesis of NO, which
led to restoration of the cNOS incoupling. We observed activation of endogenous synthesis of H2S, which interacts closely
with the nitric oxide system and is a powerful antioxidant. It
should also be noted an increase in animal survival after 24 h
by 25%. Thus, the combined use of propargylglycine and Lcysteine in rats prevented disruption of NO and H2S synthesis
in cardiac tissues in ishemia-reperfusion due to a slowing of
the development of oxidative stress, which helped to restore
cNOS coupling.
Keywords:
DL-propargylglycine; L-cysteine; oxidative stress; inducible NO synthase; constitutive NO synthases; hydrogen sulfide; focal cerebral ischemia-reperfusion.
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