Relationship of oxidative stress and antioxidant response with vaso-occlusive crisis in sickle cell anaemia

Abstract

Background: Though sickle cell anaemia (SCA) is known to promote oxidative stress, there is paucity of information on the relationship between oxidative stress and vaso-occlusive crisis (VOC).
 Objective: This study was undertaken to evaluate the relationship of oxidative stress and antioxidant response with VOC in SCA.
 Methods: A cross-sectional case-control study was carried out at University of Nigeria Teaching Hospital (UNTH), Itu- ku-Ozalla, Enugu Nigeria involving 116 individuals which included 36 SCA subject, 40 sickle cell carriers (AS) and 40 healthy individuals (AA). Baseline information as well as the frequency of VOC was obtained from the participants and anaemia as well as oxidative stress and antioxidant indices were assessed in blood.
 Results: Anaemia was prevalent (88.9 %) in SCA individuals compared to AS (52.5%) and AA (47.5 %) individuals. Nitric oxide scavenging (NOS) and superoxide dismutase (SOD) activities as well as glutathione level were significantly (p<0.005) lower while catalase activity was higher in SCA individuals compared to controls (AA and AS). Higher malondialdehyde (MDA) level was associated with very severe VOC while low level of NOS activity was associated with severe VOC in SCA individuals.
 Conclusion: Sickle cell anaemia exhibited oxidative stress and alteration in the levels of antioxidant indices which was pos- sibly associated with vaso-occlusive crisis.
 Keywords: Sickle cell anaemia; oxidative stress; antioxidant; vaso-occlusive crisis.

A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia

“…The importance of the spleen in preventing the development of autoimmune processes has been demonstrated in studies which have documented high autoantibody titres after splenectomy [ 68 ]. Moreover, chronic inflammation [ 28 ] and alloimmunisation by multiple transfusions have also been implicated in the development of autoantibodies, but these have not been fully confirmed in clinical studies [ 27 , 66 , 67 ]). The coexistence of SCD and autoimmune disease is difficult to treat as those receiving steroids, which are used to control the inflammatory response, experience repeated VOC [ 69 , 70 , 71 ].…”

“…Oxidative stress is an important contributor to the pathogenesis of sickle cell anaemia (SCD) and associated complications such as sickling, vaso-occlusion, and ischemia–reperfusion injury [ 2 , 27 , 36 , 75 , 76 ]. Oxidative stress occurs due to an imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the ability of antioxidant agents, including enzymes such as superoxide dismutases, catalase, and glutathione peroxidase, to neutralise them [ 28 , 36 , 77 ]. Patients with SCD are frequently exposed to oxidative stress, and studies have found higher levels of ROS in the RBCs of SCD patients compared to healthy controls.…”

“…Patients with SCD are frequently exposed to oxidative stress, and studies have found higher levels of ROS in the RBCs of SCD patients compared to healthy controls. The concentration of the reactive intermediates generated from the oxidative reactions has often been used as markers of disease severity [ 28 , 78 ], and the mechanisms leading to oxidative stress in SCD patients’ red blood cells (RBCs) are well established. Some of these include haemoglobin (Hb) autoxidation.…”

“…When SaQ1234567890 */haemoglobin is released into the bloodstream as a result of haemolysis, superoxide (O 2 ) produced, which can dismutate into hydrogen peroxide (H 2 O 2 ) and serve as a starting point for additional oxidative reactions [ 9 , 79 ]. Apart from haemoglobin (Hb) oxidation, other factors enhancing ROS production include ischemia–reperfusion injury caused by oxygen deprivation [ 12 ], which has been reported to promote the activation of pro-inflammatory mediators such as xanthine oxidase, NADPH oxidase, nitric oxide synthase, and lipoxygenase [ 2 , 28 ]. Another factor contributing to the excessive ROS in SCD patients is the release of iron and heme from unstable HbS, which may catalyse the Fenton reaction.…”

“…The innate and adaptive immune responses in SCD are impaired and cannot effectively protect against infection [25,26] with some researchers reporting that the persistent activation of the innate immune system results in the generation of excessive amounts of reactive oxygen species (ROS) (13,(28)(29)(30). According to Ahmad and Ahsan [27], Engwa et al [28] and Atiku et al [10] elevated amounts of reactive species induce oxidative stress and tissue injury, while other reports have revealed that the adaptive immune cells are also dysfunctional, resulting in lower antibody levels compared to healthy individuals [24]. In addition, preliminary studies have revealed that the number of T and B cells, as well as their function, are impaired [24,26,29].…”