RESUMO
INTRODUCTION: Primary Sjögren's syndrome (pSS) is a chronic inflammatory disease primarily affects exocrine glands dysfunction. Oxidative stress (OS) is a phenomenon occurring as a result of an imbalance between the generation of free radicals and antioxidant defense system. Hence, we aimed to establish the status of OS and inflammatory response according to the pSS disease activity index. In this context, we investigated malondialdehyde (MDA), and antioxidant enzymes during pSS. The possible association between MDA and nitric oxide (NO) levels and between MDA and some pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IL-33). METHODS: The study has been conducted on 53 pSS patients. The antioxidant enzymes, represented by glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD), were estimated by a colorimetric activity kit. Whereas, MDA value was assessed by measuring thiobarbituric acid reactive substances. Moreover, pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IL-33) and NO were respectively quantified by enzyme-linked immunosorbent assays (ELISA) and the modified Griess. RESULTS: Interestingly, we report a notable reduction in our pSS patients' antioxidant enzyme activity, while NO, MDA and proinflammatory cytokines values were significantly increased. pSS patients with higher disease activity had much stronger increases in NO and MDA levels. No significant difference was assessed in CRP level. Additionally, substantial significant correlations between plasmatic NO and MDA levels and between MDA, NO and IL-1ß, IL-6, TNF-α cytokines were reported. However, no significant association was found between NO, MDA and IL-33 concentrations. CONCLUSION: Collectively, our data showed altered oxidant-antioxidant balance in pSS patients. MDA, NO, IL-1ß, IL-6, TNF-α seem to be good indicators in monitoring disease activity. Oxidative stress was closely related to inflammation in pSS. Exploiting this relationship might provide valuable indicators in the follow-up and prognosis of pSS with a potential therapeutic value.
Assuntos
Biomarcadores , Citocinas , Malondialdeído , Óxido Nítrico , Estresse Oxidativo , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/metabolismo , Feminino , Pessoa de Meia-Idade , Malondialdeído/sangue , Biomarcadores/sangue , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Masculino , Citocinas/sangue , Adulto , Superóxido Dismutase/sangue , Catalase/sangue , Inflamação/sangue , Glutationa Peroxidase/sangue , Idoso , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Antioxidantes/metabolismoRESUMO
We aimed to investigate ampicillin (AMP) mechanisms in microbiota-gut-brain axis. We evaluated its effect on two gut and brain regions and behavioral performances. We administred AMP (1 g/l) to BALB/c mice for 21 days. Then, we analyzed body weigth change, stool consistency scoring, gut length, intestinal microbiota composition, nitric oxide synthase 2 (NOS2) expression and tissue integrity. We subsequently evaluated NOS2, GFAP, CD68 and NFL cerebral expression and spatial memory.Interestingly, our data showed gut microbiota disruption, NOS2 upregulation and tissue damage, associated to cerebral NOS2, GFAP, CD68 and NFL over-expression and behavioral alteration. Antiobiotic therapy should be prescribed with great caution.
Assuntos
Ampicilina , Eixo Encéfalo-Intestino , Disbiose , Microbioma Gastrointestinal , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II , Animais , Camundongos , Ampicilina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Disbiose/induzido quimicamente , Óxido Nítrico Sintase Tipo II/metabolismo , Masculino , Eixo Encéfalo-Intestino/fisiologia , Eixo Encéfalo-Intestino/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Antibacterianos/farmacologia , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Modelos Animais de Doenças , Doenças Neurodegenerativas/induzido quimicamenteRESUMO
BACKGROUND: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. It is characterized by a gradual decrease in cognitive function and is considered a disorder in which the intensifying neuronal loss. The autopsy is considered the gold standard for the diagnosis of AD and non-AD dementia. OBJECTIVE: Our study aims to clarify the involvement of neuroinflammation processes in brain lesions of AD. METHODS: The defunct was admitted to the forensic medicine department of Issad Hassani Hospital (Algeria). In order to recover the brain, an autopsy was performed within 24 hours of death and then immediately fixed in formaldehyde to maintain structural brain integrity for histological and immunohistochemical analysis. RESULTS: Our findings indicate the presence of tissue lesions in the specific brain regions: right middle frontal gyrus, right cingulate gyrus, right putamen and globus pallidus, right caudate nucleus, right hippocampus, inferior parietal lobule, left parahippocampal gyrus, and left hippocampus. Notably, there is a predominant occurrence of lesions: granulovacuolar degeneration, Hirano bodies, cotton-wool, and neuritic plaques. The causes of neurodegenerative processes are probably related to TNF-α, IL-1ß, and TGF-ß production and iNOS expression by the NF-κB activation pathway in the R-HP, inducing necroptosis. CONCLUSIONS: The occurrence of neuroinflammatory responses is linked to tissue lesions in AD. The production of inflammatory cytokines is the basis of this process, which ultimately leads to the necroptosis, which is triggered by neuroinflammation amplification. The inhibition of neuroinflammation by targeting TNF-α/iNOS could stop tissue damage, this may be a promising therapeutic pathway.