Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load

Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increa...

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Published in:	PLoS neglected tropical diseases 2021-03, Vol.15 (3), p.e0009214-e0009214
Main Authors:	da Silva, Pedro Henrique Lopes, de Castro, Katherine Kelda Gomes, Mendes, Mayara Abud, Calvo, Thyago Leal, Leal, Júlia Monteiro Pereira, Hacker, Mariana de Andréa Vilas-Boas, Nery, José Augusto da Costa, Sarno, Euzenir Nunes, Lourenço, Roberto Alves, Moraes, Milton Ozório, Lara, Flávio Alves, Esquenazi, Danuza
Format:	Article
Language:	eng
Subjects:	Accumulation Age Aged patients Ageing Aging Binding sites Biology and Life Sciences Biomolecules Biopsy Carbonyls Damage accumulation Demographic aspects Developing countries Development and progression Enzymes Free radicals Gene expression Geriatrics Health aspects Health care Immune system Infectious diseases Laboratories LDCs Leprosy Malondialdehyde Medicine and Health Sciences Mitochondria Molecules Older people Oxidation Oxidative stress Physiological aspects Population Proteins Reactive oxygen species Target recognition Tropical diseases
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Summary:	Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.
ISSN:	1935-2735 1935-2727 1935-2735