The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells.
Toxicol In Vitro
; 60: 237-244, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31175926
Pyridostigmine bromide (PB), an acetylcholinesterase (AChE) enzyme inhibitor. Experimental evidence showed that when combined with other drugs or exercise, PB caused extensive neural and/or systemic oxidative stress. However, no studies have been conducted on the genetic influence associated with basal oxidative superoxide-hydrogen peroxide (S-HP) imbalance, such as that triggered by Val16Ala-SOD2 single nucleotide polymorphism (SNP, rs4880). This SNP, (homozygous genotypes) has been associated with several chronic degenerative disorders. Therefore, we evaluated whether the SOD-SNP could alter cyto-genotoxic effects triggered by different PB-concentrations in peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from volunteers carrying different SOD2-genotypes and were cultured with various concentrations of PB. PB effects in quantity of enzyme AChE, mortality rate, oxidative stress markers, and DNA damage were assessed. Protein and gene expression of antioxidant enzymes, apoptotic markers and DNA repair enzyme, were evaluated in 24â¯h cultures. In general, PB up-regulated expression of antioxidant enzymes, and did not trigger apoptotic events. However, AA-PBMCs seemed more sensitive to PB exposure, in a protein decrease of the enzyme AChE by 10%, cell-mortality at concentrations of 20 and 40â¯ng/mL, protein carbonylation, and DNA damage, as analyzed by the Comet assay. Contrarily, PB demonstrated cyto-genoprotective effects on V-allele cells. These results indicated that genetic factors that increase HP-release may affect PB efficiency and safety.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Brometo de Piridostigmina
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Superóxido Dismutase
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Leucócitos Mononucleares
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Inibidores da Colinesterase
Limite:
Adolescent
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Adult
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Humans
Idioma:
En
Revista:
Toxicol In Vitro
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido