Oxidative Stress, DNA Damage, Inflammation and Endothelial Dysfunction in Snakebite-Induced Acute Kidney Injury

Abstract

Snakebite-induced acute kidney injury (SAKI) is a life-threatening complication. Despite its impact on public health, the understanding of the underlying cellular and molecular mechanisms remains limited. There is a lack of studies investigating the role of oxidative stress, oxidative deoxyribonucleic acid (DNA) damage, inflammation, and endothelial dysfunction in SAKI. This study aims to address this knowledge gap. Biomarkers of oxidative stress, including oxidative DNA damage, inflammation, and endothelial dysfunction were assessed in 30 patients with SAKI and 30 healthy controls. Malondialdehyde (MDA), protein carbonyl content (PCC), advanced glycation end products (AGEs), 8-hydroxy-2’-deoxyguanosine (8-OHdG), ferric reducing ability of plasma (FRAP), high-sensitivity C-reactive protein (hs-CRP), and nitric oxide (NO) were used as biomarkers. We found significantly elevated levels of MDA (2.1590±0.68221 µmol/L vs 0.8769±0.2958 µmol/L, p = <0.001), PCC (0.0905±0.040 nmol/L vs 0.0501±0.024 nmol/L, p = <0.001) and 8-OHdG (47.0757±37.09105 ng/mL vs 18.8450±9.31479 ng/mL, p = <0.001) in SAKI patients compared to controls, indicating increased oxidative damage to lipids, proteins, and DNA respectively. Although AGEs showed higher levels in SAKI patients, the difference was not significant. FRAP levels were significantly reduced [0.214 (0.051-0.489) mmol/L vs 0.470 (0.136-0.564) mmol/L, p = 0.024], indicating compromised antioxidant capacity. Significantly elevated levels of hs-CRP [40.18 (16.96-77.56) mg/L vs 1.44 (0.5-4.45) mg/L, p = <0.001] and NO [25.59 (22.75-28.43) µmol/L vs 14.218 (11.37-16.35) µmol/L, p = <0.001] confirmed the presence of inflammation and endothelial dysfunction in these patients. Our study demonstrated oxidative stress, including oxidative DNA damage, inflammation, and endothelial dysfunction, in SAKI patients. Understanding these intricate mechanisms could lead to the development of novel diagnostic tools and therapeutic strategies.