Malarial Infection of Female BWF1 Lupus Mice Alters the Redox State in Kidney and Liver Tissues and Confers Protection against Lupus Nephritis

Saleh Al-Quraishy,Mostafa A Abdel-Maksoud,Gamal Badr,Azza El-Amir,Fathy A Abdel-Ghaffar

doi:10.1155/2013/156562

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by an imbalanced redox state and increased apoptosis. Tropical infections, particularly malaria, may confer protection against SLE. Oxidative stress is a hallmark of SLE. We have measured changes in the levels of nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), and reduced glutathione (GSH) in both kidney and liver tissues of female BWF1 lupus mice, an experimental model of SLE, after infection with either live or gamma-irradiated malaria. We observed a decrease in NO, H2O2, and MDA levels in kidney tissues after infection of lupus mice with live malaria. Similarly, the levels of NO and H2O2 were significantly decreased in the liver tissues of lupus mice after infection with live malaria. Conversely, GSH levels were obviously increased in both kidney and liver tissues after infection of lupus mice with either live or gamma-irradiated malaria. Liver and kidney functions were significantly altered after infection of lupus mice with live malaria. We further investigated the ultrastructural changes and detected the number of apoptotic cells in kidney and liver tissues in situ by electron microscopy and TUNEL assays. Our data reveal that infection of lupus mice with malaria confers protection against lupus nephritis.

Highlights

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that is characterized by the appearance of autoantibodies, against nuclear components [1]
The percentage of apoptotic cells in peripheral blood is significantly higher in SLE patients than in normal healthy patients, and the progression of human lupus nephritis is directly proportional to the increase in the rate of apoptosis [7]
The effect of malarial infection on oxidative stress markers in the SLE experimental model was measured by determining the levels of nitric oxide (NO), H2O2, and MDA in kidney and liver samples of the three experimental groups of female BWF1 mice, whereas GSH was the only antioxidant parameter measured in these tissues

Summary

Introduction

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that is characterized by the appearance of autoantibodies, against nuclear components [1]. Because of its multifactorial etiology, which includes genetic, hormonal, and environmental triggers, the molecular mechanisms underlying this disease remain largely unknown. Increased ROS generation has been reported to promote inflammation, necrosis, and apoptosis in chronic kidney disease [4]. Apoptosis plays an important role in SLE, and higher apoptosis rates lead to the production of autoantibodies, subsequently triggering disease activity [6]. The percentage of apoptotic cells in peripheral blood is significantly higher in SLE patients than in normal healthy patients, and the progression of human lupus nephritis is directly proportional to the increase in the rate of apoptosis [7]. The delayed clearance of apoptotic cells induced by ROS production may prolong

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