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<title>Saudi Pharmaceutical Journal December 2022</title>
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<originInfo>
<place><placeTerm type="text">Arab Saudi</placeTerm></place>
<publisher>University of Jeddah</publisher>
<dateIssued>2022</dateIssued>
<issuance>monographic</issuance>
<edition>December 2022</edition>
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<languageTerm type="text">Indonesia</languageTerm>
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<note>abstract
Background: The therapeutic activity of Glyceryl trinitrate (GTN) is mainly regulated by liberating nitric
oxide (NO) and reactive nitrogen species (RNS). During this biotransformation, oxidative stress and lipid

peroxidation inside the red blood cells (RBCs) occur. Hemoglobin tightly binds to NO forming methe-
moglobin altering the erythrocytic antioxidant defense system.

Aim: The principal objective of our research is to show the ameliorating effect of L-ascorbic acid for the
deleterious effects of chronic administration of nitrovasodilator drugs used in cardiovascular diseases
such as oxidative stresses and tolerance.
Method: We studied some biochemical parameters for the oxidative stress using groups of high sucrose/-
fat (HSF) diet Wistar male rats chronically orally administered different concentrations of Isosorbide-5-
mononitrate (ISMN) 0.3 mg/kg, 0.6 mg/kg and 1.2 mg/kg. Afterwards, we evaluated the role of L-ascorbic
acid against these biochemical changes in cardiac tissues.
Results: Chronic treatment with organic nitrates caused elevated serum levels of lipid peroxidation,
hemoglobin derivatives as methemoglobin and carboxyhemoglobin, rate of hemoglobin autoxidation,

the cellular levels of the pro-inflammatory cytokines marker (NF-jB) and apoptosis markers (caspase-
3) in the myocardium muscles in a dose-dependent manner. Meanwhile, such exposure caused a decline

in the enzymatic effect of SOD, GSH and CAT accompanied by a decrease in the level of mitochondrial
oxidative stress marker (nrf2) in the myocardium muscles and a decrease in the serum iron and total
iron-binding capacity (TIBC) in a dose-dependent manner. Concomitant treatment with L-ascorbic acid
significantly diminished these changes for all examined parameters.
Conclusion: Chronic administration of organic nitrates leads to the alteration of the level of oxidative

stress factors in the myocardium tissue due to the generation of reactive oxygen species. Using L- ascorbic acid can effectively ameliorate such intoxication to overcome nitrate tolerance.</note>
<subject authority=""><topic>Oxidative stress</topic></subject>
<subject authority=""><topic>L-ascorbic acid</topic></subject>
<subject authority=""><topic>Organic nitrates</topic></subject>
<subject authority=""><topic>Methemoglobin</topic></subject>
<classification></classification><identifier type="isbn"></identifier><location>
<physicalLocation>PERPUSTAKAAN SEKOLAH TINGGI ILMU KESEHATAN SAMARINDA REPOSITORY</physicalLocation>
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<sublocation>Perpus.Akfarsam (Jurnal Farmasi Internasional)</sublocation>
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