RESUMO
Many studies have shown that the pathogenesis of liver injury includes oxidative stress. MicroRNA-122 may be a marker for the early diagnosis of drug-induced liver injury. However, the relationship between microRNA-122 and oxidative stress in anti-tuberculosis drug-induced liver injury remains unknown. We measured changes in tissue microRNA-122 levels and indices of oxidative stress during liver injury in mice after administration of isoniazid, a first-line anti-tuberculosis drug. We quantified microRNA-122 expression and indices of oxidative stress at 7 time points, including 1, 3, and 5 days and 1, 2, 3, and 4 weeks. The tissue microRNA-122 levels and oxidative stress significantly changed at 3 and 5 days, suggesting that isoniazid-induced liver injury reduces oxidative stress and microRNA-122 expression compared to in the control group (P < 0.05). Notably, over the time course of isoniazid-induced liver injury, mitochondrial ribosome protein S11 gene, the target of microRNA-122, began to change at 5 days (P < 0.05). The tissue microRNA-122 profile may affect oxidative stress by regulating mitochondrial ribosome protein S11 gene during isoniazid-induced liver injury, which may contribute to the response mechanisms of microRNA-122 and oxidative stress.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , MicroRNAs/genética , Estresse Oxidativo/genética , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Feminino , Expressão Gênica , Isoniazida/efeitos adversos , Testes de Função Hepática , Masculino , Metalotioneína/metabolismo , Camundongos , Oxirredução , Fatores de TempoRESUMO
We investigated the association between interleukin (IL)-6 and IL-10 gene polymorphisms and the susceptibility to pulmonary tuberculosis (PTB). DNA samples were obtained from 191 Han Chinese patients with PTB and 191 healthy control subjects. IL-6 (-572, -174, -597) and IL-10 (-1082, -819) polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism. The IL-6 -572 C/C and IL-10 -819 T/T genotypes were observed less frequently in the case group than in the control group, with crude odds ratios of 0.591 [95% confidence interval (CI) = 0.381-0.917] and 0.401 (95%CI = 0.257-0.627), respectively. A significant association remained after adjusting for environmental factors in multivariate logistic analysis. The homozygote genotypes of IL-6 -572 and IL-10 -819 had an adjusted OR of 0.565 (95%CI = 0.356-0.898) and 0.341 (95%CI = 0.210-0.553), respectively. These results indicate that the mutant heterozygote IL-10 -1082 A/ G+G/G genotype and the homozygote IL-10 -819 T/T genotype have a combined effect on PTB. These results suggest that the IL-6 -572 C/C and IL-10 -819 T/T genotype polymorphisms are protective factors against PTB.
Assuntos
Etnicidade , Interleucina-10/genética , Interleucina-6/genética , Tuberculose Pulmonar/genética , Sequência de Bases , Estudos de Casos e Controles , China , Primers do DNA , HumanosRESUMO
We examined the relationships between N-transacetylase 2 (NAT2), cytochrome P450 (CYP) 2E1 enzyme, glutathione S-transferase M1, T1 (GSTM1/GSTT1) gene polymorphisms, and anti-tuberculosis drug-induced hepatic injury (ADIH). A one-to-one matched case-control study was carried out using clinical data. NAT2, CYP2E1, GSTM1, and GSTT1 polymorphisms were identified in 173 pairs of research subjects. Statistical analysis was performed to determine risk factors of ADIH. The results showed that low body mass index and alcohol consumption were risk factors of ADIH, with odds ratios of 6.852 and 3.203, respectively. The frequencies of NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and the GSTM1 null genotype were higher in the case group than in the control group, with odds ratios of 2.260, 2.696, 4.714, and 2.440, respectively. GSTT1 was not found to be related to ADIH. Interactive analysis showed that NAT2 slow acetylator and the GSTM1 null genotype were mutually synergistic, while an antagonistic relationship was observed between the CYP2E1 wild-type genotype and the other 3 genetic types. The risks of hepatic injury were higher after anti-tuberculosis therapy in patients carrying the NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and GSTM1 null genotype.