Abstract
ABSTRACTObjective To investigate the relation between oxidative stress markers, human papillomavirus infection and cervical cancer precursor lesions.Methods The study comprised women aged 14 to 60 years living in communities located by Amazon rivers in the state of Pará (Itaituba, Limoeiro do Ajuru and Bragança, 126, 68 and 43 women respectively). Papanicolau smears and polymerase chain reaction tests for human papillomavirus DNA detection were performed. Blood samples were collected to test malondialdehyde, total and oxidized glutathione levels.Results Malondialdehyde, total and oxidized glutathione concentrations did not differ significantly (p>0.05) between women with and without low-grade squamous intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL) were almost five times higher in human papillomavirus-positive compared to human papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically significant difference; p<0.05). Malondialdehyde levels did not differ significantly (p>0.05) between human papillomavirus-positive and human papillomavirus-negative women living in remaining communities. Significant (p<0.05) differences in total glutathione levels between human papillomavirus-positive and human papillomavirus-negative women (8.20μg/mL and 1.47μg/mL, respectively) were limited to those living in Bragança.Conclusion Malondialdehyde and total glutathione levels were significantly associated with human papillomavirus infection. However, lack of similar associations with squamous lesions suggest oxidative stress alone does not explain correlations with cervical carcinogenesis. Other factors may therefore be involved.
Highlights
Cervical cancer is a curable disease when diagnosed early; still it is associated with high morbidity and mortality rates in developing countries.[1]. Cervical carcinogenesis depends upon some human papillomavirus (HPV)associated factors, such as HPV type, immune system and genetics.[2]. Oxidative stress is responsible for the production of reactive oxygen species (ROS) and is thought to play an important role in this process
Two cooperative mechanisms are thought to occur between oxidative stress and HPV: [1] oxidative stress genotoxic activity and HPV-induced genomic instability acting independently to generate molecular damage required to trigger the development of neoplastic cells; and [2] oxidative stress interaction with one or more stages of neoplastic initiation and/or progression induced by HPV infection.[2]
Lower GSH-Px activity, lower plasma antioxidant vitamin levels and higher MDA concentrations were documented in women suffering from cervical intraepithelial neoplasia or invasive cervical cancer compared to women in the Control Group.[7]. Higher MDA levels were reported in cervical cancer patients compared to controls,(8) along with lower levels of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and GSH-Px
Summary
Cervical cancer is a curable disease when diagnosed early; still it is associated with high morbidity and mortality rates in developing countries.[1]. Reactive oxygen species cause irreversible damage to important biomolecules, such as membrane lipids, proteins and DNA, contributing to cell injury and death This dysfunction may impact the development of cervical cancer precursor lesions as well as HPV persistence.[3]. Higher MDA levels have been reported in patients with advanced-stage compared to early-stage cancer.[4] Malondialdehyde is thought to be a potential global plasma biomarker of oxidative damage.[5] Other markers, such as glutathione and enzymes in the MDA catalytic cycle, have been associated with antioxidant defense changes and increased oxidative stress, both of which are thought to be carcinogenic factors. People living along river banks rely on traditional fishing for subsistence and commercial reasons, and are geographically widely dispersed and distributed These populations are prey to socio-economic constraints to education, housing, diet and health. Such living conditions are thought to play a significant role in high cervical cancer rates in Northern Brazil, where communities living by Amazon rivers are many, and poorly investigated
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