Oxidative Stress Markers Correlate with Renal Dysfunction and Thrombocytopenia in Severe Leptospirosis

Abstract

Abstract. Leptospirosis is a zoonotic disease that causes severe manifestations such as Weil's disease and pulmonary hemorrhage syndrome. The aim of this study was to evaluate whether reactive oxygen species (ROS) production and antioxidant reduced glutathione (GSH) levels are related to complications in patients hospitalized with leptospirosis. The ROS production and GSH levels were measured in blood samples of 12 patients and nine healthy controls using chemiluminescence and absorbance assays. We found that ROS production was higher and GSH levels were lower in leptospirosis patients compared with healthy individuals. Among patients, GSH depletion was correlated with thrombocytopenia and elevated serum creatinine, whereas a strong positive correlation was observed between ROS production and elevated serum potassium. Additional investigation of the biological significance of ROS production and GSH levels is warranted as they may guide the development of novel adjuvant therapies for leptospirosis targeting oxidative stress.

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

“…Oxidative stress is known to be responsible for tissue damage in other diseases. For example, in severe sepsis, it has been demonstrated that increased production of ROS and RNS together with depletion of anti-oxidants results in increased oxidative stress and this is associated with tissue injury and disease severity[ 18 ].Similar findings have been recorded in human leptospirosis [ 18 , 21 – 23 ]. It is thought that the pathogenesis of leptospirosis is significantly different from bacterial sepsis.…”

The adaptive transcriptional response of pathogenicLeptospirato peroxide reveals new defenses against infection-related oxidative stress

“…superoxide anion (  O 2 -), hydrogen peroxide, (H 2 O 2 ), hydroxyl radicals (  OH), hypochlorous acid (HOCl), and nitric oxide anion (  NO) are produced upon infection by Leptospira. Indeed, the internalization of pathogenic Leptospira by macrophages and concomitant production of these oxidants have been demonstrated in vitro (6), and leptospirosis-associated oxidative stress has been observed in leptospirosis patients (7) and infected animals (8). Consistent with these findings was the demonstration that catalase, that catalyzes the degradation of H 2 O 2 , is required for Leptospira interrogans virulence (9).…”

“…The increased expression of heme biosynthesis genes, which is PerR-independent and probably participated in the peroxidase activities of catalase, AhpC and CCP, is not represented here.When the level of ROS overwhelms the detoxification capacity of the up-regulated peroxidases and becomes damaging for the cellular constituents (B), in addition of a higher production of catalase, AhpC and CCP, other machineries are up-regulated such as thiol oxido-reductases (including thioredoxin, DsbD, etc. )(7), molecular chaperones (8) and DNA repair proteins(9). The increased expression of the aforementioned machineries is PerRindependent and probably involves other transcriptional regulator (TFs) and noncoding RNAs.Supporting information.…”

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

“…PMN may act against Leptospira using soluble factors like antimicrobial peptides or oxidative stress [7–9]. The production of reactive oxygen species (ROS) seems to be more elevated in leptospirosis patients compared to controls, and is correlated to levels of markers of tissue injury, although the source of ROS and the contribution of PMN was not evaluated [10]. Recent findings suggest that the production of neutrophil’s extracellular traps (NETosis) could be a reliable mechanism of defense to prevent bacterial dissemination [11].…”