Heshan Kuruppu, Maneshka Karunananda, Chandima Jeewandara, Laksiri Gomes, D M C B Dissanayake, Chathura Ranatunga, Padukkage Harshani Chathurangika, Nushara Senatilleke, Navanjana Warnakulasuriya, Rivindu H Wickramanayake, Ananda Wijewickrama, Damayanthi Idampitiya, Graham S Ogg, Gathsaurie Neelika Malavige
{"title":"Oxidative stress induced liver damage in dengue is exacerbated in those with obesity.","authors":"Heshan Kuruppu, Maneshka Karunananda, Chandima Jeewandara, Laksiri Gomes, D M C B Dissanayake, Chathura Ranatunga, Padukkage Harshani Chathurangika, Nushara Senatilleke, Navanjana Warnakulasuriya, Rivindu H Wickramanayake, Ananda Wijewickrama, Damayanthi Idampitiya, Graham S Ogg, Gathsaurie Neelika Malavige","doi":"10.1101/2025.03.18.25324170","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obesity and diabetes are risk factors for severe dengue. As there are limited data on the association of obesity with liver dysfunction and oxidative stress in patients with acute dengue, we investigated liver dysfunction associated with obesity, oxidative stress and inflammatory markers, in a large cohort of patients with varying severity of acute dengue.</p><p><strong>Methods: </strong>577 adults dengue patients with acute disease, presenting with a duration of illness ≤ 4 days, were enrolled and followed up from admission to discharge, with clinical and laboratory features recorded. Aspartate transaminase (AST), alanine transaminase (ALT), C-reactive protein, ferritin, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) levels were measured, along with the height, weight and waist circumference.</p><p><strong>Results: </strong>AST, ALT, CRP and ferritin levels were significantly higher in patients with central obesity (waist circumference of ≥80cm in women or ≥90cm in men) compared to leaner individuals. ALT and CRP levels were also significantly higher in patients with a BMI of ≥ 23.9 kg/m <sup>2</sup> . 4-HNE levels significantly increased with the rise in AST levels and with ALT levels although not significant. In contrast, MDA levels gradually decreased with the rise in AST levels and ALT levels. There were no differences in 4-HNE and MDA levels in relation to clinical disease severity. However, MDA levels were significantly higher in younger individuals, and leaner individuals with a normal BMI. Furthermore, MDA levels inversely correlated with serum ferritin levels, while AST, ALT and CRP levels significantly correlated ferritin levels.</p><p><strong>Conclusions: </strong>4-HNE and MDA which are markers of lipid peroxidation, appear to play different roles in the pathogenesis of dengue, which should be further investigated for identification of therapeutic targets for treatment of dengue.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957102/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv : the preprint server for health sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2025.03.18.25324170","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Obesity and diabetes are risk factors for severe dengue. As there are limited data on the association of obesity with liver dysfunction and oxidative stress in patients with acute dengue, we investigated liver dysfunction associated with obesity, oxidative stress and inflammatory markers, in a large cohort of patients with varying severity of acute dengue.
Methods: 577 adults dengue patients with acute disease, presenting with a duration of illness ≤ 4 days, were enrolled and followed up from admission to discharge, with clinical and laboratory features recorded. Aspartate transaminase (AST), alanine transaminase (ALT), C-reactive protein, ferritin, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) levels were measured, along with the height, weight and waist circumference.
Results: AST, ALT, CRP and ferritin levels were significantly higher in patients with central obesity (waist circumference of ≥80cm in women or ≥90cm in men) compared to leaner individuals. ALT and CRP levels were also significantly higher in patients with a BMI of ≥ 23.9 kg/m 2 . 4-HNE levels significantly increased with the rise in AST levels and with ALT levels although not significant. In contrast, MDA levels gradually decreased with the rise in AST levels and ALT levels. There were no differences in 4-HNE and MDA levels in relation to clinical disease severity. However, MDA levels were significantly higher in younger individuals, and leaner individuals with a normal BMI. Furthermore, MDA levels inversely correlated with serum ferritin levels, while AST, ALT and CRP levels significantly correlated ferritin levels.
Conclusions: 4-HNE and MDA which are markers of lipid peroxidation, appear to play different roles in the pathogenesis of dengue, which should be further investigated for identification of therapeutic targets for treatment of dengue.