Serum Oxidative-Antioxidative Status in Patients With Alkaptonuria

Abstract

Background Alkaptonuria (AKU) is a rare genetic disease associated with the deposition of melanin-like pigments (ochronosis) in connective tissues. However, data regarding the effect of oxidative stress products on disease pathogenesis are limited. The purpose of this study was to investigate oxidative stress and related factors in patients with alkaptonuria and compare the findings with those in healthy control subjects. Methods The study sample comprised of 21 AKU patients and 19 age- and sex-matched healthy controls. Serum samples were obtained to detect the total antioxidative capacity (TAC), and oxidation degradation products of thiobarbituric acid-reactive substances, protein carbonyls, advanced oxidation protein products, and homogentisic acid levels in urine were determined. Results Serum TAC, oxidation degradation products of thiobarbituric acid-reactive substances, and protein carbonyl levels in the AKU group were higher than those measured for the control subjects, and the difference was statistically significant (P < 0.05). Moreover, a positive correlation was found between the patient’s serum protein carbonyl, patient’s age and AKU severity score (r = 0.492 and 0.746, respectively; P < 0.05). Furthermore, the protein carbonyl serum levels can be used to predict the disease severity score in alkaptonuria patients (P < 0.05). Conclusions In sum, the study results provide further support for the role of oxidation in the pathogenesis of alkaptonuria, suggesting presence of a more complex relationship than what has been previously assumed. Thus, further studies are needed to clarify these conflicting results.

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“…Vitamin C has been proposed as its anti-oxidant properties might be able to stop the oxidation of homogentisic acid (HGA) into harmful metabolites, but later on, found to not affect levels of HGA in urine. 30 In addition, low tyrosine and phenylalanine diet has also been proposed as these two amino acids are degraded into HGA but the effects of going on the diet were not studied on the long term. 31 Additionally, nitisinone was proposed since it is a potent inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase which produces HGA, but it can increase serum tyrosine levels which may lead to corneal irritation.…”

Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease

“…Therefore, in AKU, besides inflammation, patients also suffer from significant oxidative stress caused by high systemic levels of HGA and its products. Despite these recent results, there is still a critical necessity to identify methods for monitoring AKU progression, in particular, its level of oxidative stress, and to evaluate response to treatment (22). In the study of Braconi et al .…”

“…Therefore, in AKU, besides inflammation, patients also suffer from significant oxidative stress caused by high systemic levels of HGA and its products. Despite these recent results, there is still a critical necessity to identify methods for monitoring AKU progression, in particular, its level of oxidative stress, and to evaluate response to treatment (22). In the study of Braconi et al (15), it was described as the first proteomic characterization of plasma and serum samples of 6 individuals with AKU, highlighting proteomic alterations in AKU samples and showing interesting similarities with other rheumatic diseases and further supporting the existence of HGA-related oxidative stress and inflammation in AKU.…”