Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections

Abstract

Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management.

Differences in serum markers of oxidative stress in well controlled and poorly controlled asthma in Sri Lankan children: a pilot study

“…There are different biomarkers to assess the redox status of tissues including free radicals, lipid peroxidation products and alterations of antioxidant levels (as a surrogate marker). In this study serum nitrites, nitrates and TAOC were used as these assays have been used and validated for the local population previously for non-asthma related pathologies including leptospirosis [ 28 , 35 , 37 ], dengue haemorrhagic fever [ 34 ] and Parkinson disease [ 38 ]. Other studies which measured pro-oxidant levels in patients with asthma used exhaled nitric oxide (eNO) as this is a sensitive and specific marker of airway inflammation and a higher level of eNO was recorded in patients with asthma as compared to healthy controls [ 39 – 41 ].…”

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

“…High levels of protein carbonyl (>C=O) groups have been observed in some diseases, including Alzheimer's disease (AD), rheumatoid arthritis, diabetes, sepsis, chronic renal failure, and respiratory distress syndrome (Pullaiah et al, 2018). In microbial infections (e.g., leptospirosis), induced oxidative stress like the protein carbonyls are of diagnostic value (Fernando et al, 2016). Also, it was reported that urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is a DNA oxidative stress biomarker and a risk factor for cancer, atherosclerosis, and diabetes (Wu et al, 2004; Kawai et al, 2018).…”

Leptospirosis: challenges in diagnosis, and predictors of severity

“…We also included 30 patients with critical phase dengue, and 30 healthy controls (table 5). 36 Lipid peroxide levels were measured using the Ferrous Oxidation-Xylenol orange (FOX2) assay. Our findings showed that lipid peroxide levels were high in patients with leptospirosis, and were low in patients with dengue and healthy controls.…”