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      Role of Uric Acid in Semen

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      Publication date (Electronic):
      Journal: Biomolecules
      Publisher: MDPI
      Keywords: uric acid, sperm, semen quality, antioxidant

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          Abstract

          Since 1963, various research studies and reports have demonstrated the role of uric acid (2,6,8-trihydroxypurine), an end product of adenosine and guanosine catabolism, on semen quality and sperm function. However, this effect has not yet been collectively discussed, even though uric acid has been a well-recognized constituent in semen. Here, we systematically and comprehensively discuss and summarize the role/effect of uric acid in semen quality by searching the main databases for English language articles considering this topic. Additionally, certain significant and relevant papers were considered to support discussions and perceptions. In conclusion, uric acid contributes to maintaining and enhancing sperm motility, viability, and morphology; therefore, protecting sperm function and fertilizing ability. This contribution is performed mainly by neutralizing the damaging effect of oxidizing (e.g., endogenous free radicals and exogenous toxins) and nitrating agents and enhancing certain bioactive enzymes in spermatozoa. In contrast, high levels of uric acid may induce adverse effects to sperm function, at least in part, by reducing the activity of vital enzymes in spermatozoa. However, further research, mainly clinical, is still required to fully explore the role/effect of uric acid in semen.

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          Towards the physiological function of uric acid.

          Esther Becker (1993)
          Uric acid, or more correctly (at physiological pH values), its monoanion urate, is traditionally considered to be a metabolically inert end-product of purine metabolism in man, without any physiological value. However, this ubiquitous compound has proven to be a selective antioxidant, capable especially of reaction with hydroxyl radicals and hypochlorous acid, itself being converted to innocuous products (allantoin, allantoate, glyoxylate, urea, oxalate). There is now evidence for such processes not only in vitro and in isolated organs, but also in the human lung in vivo. Urate may also serve as an oxidisable cosubstrate for the enzyme cyclooxygenase. As shown for the coronary system, a major site of production of urate is the microvascular endothelium, and there is generally a net release of urate from the human myocardium in vivo. In isolated organ preparations, urate protects against reperfusion damage induced by activated granulocytes, cells known to produce a variety of radicals and oxidants. Intriguingly, urate prevents oxidative inactivation of endothelial enzymes (cyclooxygenase, angiotensin converting enzyme) and preserves the ability of the endothelium to mediate vascular dilatation in the face of oxidative stress, suggesting a particular relationship between the site of urate formation and the need for a biologically potent radical scavenger and antioxidant.
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            Oxidative stress and endothelial dysfunction: clinical evidence and therapeutic implications.

            Kensuke Noma, Tatsuya Maruhashi, Yukihito Higashi … (2014)
            An imbalance of nitric oxide (NO) and reactive oxygen species (ROS), so-called "oxidative stress," may promote endothelial dysfunction, leading to cardiovascular complications. Activation of nicotinamide-adenine dinucleotide phosphate oxidase, xanthine oxidase, cyclooxygenase, and mitochondrial electron transport, inactivation of the antioxidant system, and uncoupling of endothelial NO synthase lead to oxidative stress along with an increase in ROS production and decrease in ROS degradation. Although experimental studies, both in vitro and in vivo, have shown a critical role of oxidative stress in endothelial dysfunction under the condition of excessive oxidative stress, there is little information on whether oxidative stress is really involved in endothelial function in humans. In a clinical setting, we showed an association between oxidative stress and endothelial function, especially in patients with renovascular hypertension as a model of increased oxidative stress and in patients with Gilbert syndrome as a model of decreased oxidative stress, through an increase in the antioxidant property of unconjugated bilirubin. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Comparison of Oxidative Stress/DNA Damage in Semen and Blood of Fertile and Infertile Men

              Jolanta Guz, Daniel Gackowski, Marek Foksinski … (2013)
              Abnormal spermatozoa frequently display typical features of oxidative stress, i.e. excessive level of reactive oxygen species (ROS) and depleted antioxidant capacity. Moreover, it has been found that a high level of oxidatively damaged DNA is associated with abnormal spermatozoa and male infertility. Therefore, the aim of our study was the comparison of oxidative stress/DNA damage in semen and blood of fertile and infertile men. The broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair were analyzed in the blood plasma and seminal plasma of groups of fertile and infertile subjects. These parameters include: (i) 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) levels in urine; (ii) 8-oxodG level in DNA isolated from leukocytes and spermatozoa; (iii) antioxidant vitamins (A, C and E) and uric acid. Urinary excretion of 8-oxodG and 8-oxoGua and the level of oxidatively damaged DNA in leukocytes as well as the level of antioxidant vitamins were analyzed using HPLC and HPLC/GC/MS methods. The results of our study demonstrate that 8-oxodG level significantly correlated with every parameter which describe sperm quality: sperm count, motility and morphology. Moreover, the data indicate a higher level of 8-oxodG in sperm DNA compared with DNA of surrogate tissue (leukocytes) in infertile men as well as in healthy control group. For the whole study population the median values of 8-oxodG/106 dG were respectively 7.85 and 5.87 (p = 0.000000002). Since 8-oxodG level in sperm DNA is inversely correlated with urinary excretion rate of 8-oxoGua, which is the product of OGG1 activity, we hypothesize that integrity of spermatozoa DNA may be highly dependent on OGG1 activity. No relationship between the whole body oxidative stress and that of sperm plasma was found, which suggests that the redox status of semen may be rather independent on this characteristic for other tissues.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomolecules
                Journal ID (iso-abbrev): Biomolecules
                Journal ID (publisher-id): biomolecules
                Title: Biomolecules
                Publisher: MDPI
                ISSN (Electronic): 2218-273X
                Publication date (Electronic): 31 July 2018
                Publication date Collection: September 2018
                Volume: 8
                Issue: 3
                Electronic Location Identifier: 65
                Affiliations
                Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan; sabanihani@ 123456just.edu.jo ; Tel.: +962-2-720-1000
                Author information
                https://orcid.org/0000-0002-6830-6247
                Article
                Publisher ID: biomolecules-08-00065
                DOI: 10.3390/biom8030065
                PMC ID: 6164278
                PubMed ID: 30065172
                SO-VID: a24fb441-cbce-430c-9886-a985ca607b97
                Copyright © © 2018 by the author.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 28 June 2018
                Date accepted : 26 July 2018
                Categories
                Subject: Review

                Keywords: uric acid,sperm,semen quality,antioxidant
                Data availability:
                Keywords: uric acid, sperm, semen quality, antioxidant

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