RESUMO
BACKGROUND: Acinetobacter baumannii poses a significant threat globally, causing infections primarily in healthcare settings, with high mortality rates. Its adaptability to antibiotic resistance and tolerance to various stresses, including reactive oxygen species (ROS), contribute to its persistence in healthcare environments. Previous evidence suggested that the periplasmic heat shock protein, HslJ-like protein (ABUW_2868), could be involved in oxidative stress defense in A. baumannii. In this study, we demonstrate the pivotal function of HslJ as the first line of defense against oxidative damage induced by hydrogen peroxide (H2O2). METHODS: An isogenic site-specific hslJ mutant of A. baumannii AB5075 was used to evaluate its sensitivity to H2O2, survival rate in human macrophages, biofilm, cell surface hydrophobicity, and motility. Additionally, the hslJ expression profile was measured under stress conditions and its OxyR-dependent regulation was assessed both in vitro and in a heterologous host. RESULTS: Herein, we report that HslJ is under the positive regulatory control of OxyR, which upregulates its expression in response to imipenem (IMP) and H2O2, thereby underscoring its importance in A. baumannii survival strategy. In addition, our findings revealed that the hslJ mutant displayed abrogated surface-associated motility accompanied by increased cell surface hydrophobicity (CSH), indicating also a role in maintaining cell membrane properties. CONCLUSIONS: This comprehensive understanding of HslJ multifaceted role not only enriches our knowledge of A. baumannii stress response mechanisms but also provides valuable insights for developing targeted strategies to eradicate this deadly resilient pathogen in healthcare settings.
Assuntos
Acinetobacter baumannii , Peróxido de Hidrogênio , Estresse Oxidativo , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Estresse Oxidativo/fisiologia , Peróxido de Hidrogênio/farmacologia , Humanos , Biofilmes/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas Periplásmicas/metabolismo , Proteínas Periplásmicas/genética , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologiaRESUMO
Parkinson's disease (PD) is a progressive age-related neurodegenerative disease whose annual incidence is increasing as populations continue to age. Although its pathogenesis has not been fully elucidated, oxidative stress has been shown to play an important role in promoting the occurrence and development of the disease. Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length, are also involved in the pathogenesis of PD at the transcriptional level via epigenetic regulation, or at the post-transcriptional level by participating in physiological processes, including aggregation of the α-synuclein, mitochondrial dysfunction, oxidative stress, calcium stabilization, and neuroinflammation. LncRNAs and oxidative stress are correlated during neurodegenerative processes: oxidative stress affects the expression of multiple lncRNAs, while lncRNAs regulate many genes involved in oxidative stress responses. Oxidative stress and lncRNAs also affect other processes associated with neurodegeneration, including mitochondrial dysfunction and increased neuroinflammation that lead to neuronal death. Therefore, modulating the levels of specific lncRNAs may alleviate pathological oxidative damage and have neuroprotective effects. This review discusses the general mechanisms of oxidative stress, pathological mechanism underlying the role of oxidative stress in the pathogenesis of PD, and teases out the mechanisms through which lncRNAs regulate oxidative stress during PD pathogenesis, as well as identifies the possible neuroprotective mechanisms of lncRNAs. Reviewing published studies will help us further understand the mechanisms underlying the role of lncRNAs in the oxidative stress process in PD and to identify potential therapeutic strategies for PD.
Assuntos
Estresse Oxidativo , Doença de Parkinson , RNA Longo não Codificante , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Estresse Oxidativo/fisiologia , Estresse Oxidativo/genética , Humanos , AnimaisRESUMO
The central nervous system (CNS) comprises membranes and barriers that are vital to brain homeostasis. Membranes form a robust shield around neural structures, ensuring protection and structural integrity. At the same time, barriers selectively regulate the exchange of substances between blood and brain tissue, which is essential for maintaining homeostasis. Another highlight is the glymphatic system, which cleans metabolites and waste from the brain. Traumatic brain injury (TBI) represents a significant cause of disability and mortality worldwide, resulting from the application of direct mechanical force to the head that results in a primary injury. Therefore, this review aims to elucidate the mechanisms associated with the secondary injury cascade, in which there is intense activation of glial cells, dysfunction of the glymphatic system, glutamatergic neurotoxicity, additional molecular and biochemical changes that lead to a neuroinflammatory process, and oxidative stress and in which way they can be associated with cognitive damage that is capable of lasting for an extended period.
Assuntos
Lesões Encefálicas Traumáticas , Doenças Neuroinflamatórias , Estresse Oxidativo , Lesões Encefálicas Traumáticas/metabolismo , Humanos , Animais , Doenças Neuroinflamatórias/metabolismo , Estresse Oxidativo/fisiologia , Sistema Glinfático/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Neuroglia/metabolismoRESUMO
OBJECTIVE: Thiols play an essential role in eliminating oxidative stress in cells. We aimed to evaluate the oxidative stress occurring during labor with thiol-disulfide balance. METHODS: A total of 97 healthy pregnant women in the 37th-41st gestational weeks who underwent delivery between June 2021 and August 2022 were included in the study. Elective cesarean section group 1 (n=33), vaginal deliveries group 2 (n=29), and cesarean section due to cephalopelvic disproportion group 3 (n=35) were determined. Blood samples were taken before delivery, and from the umbilical artery just after the fetus and placenta were delivered. Serum native thiol (µmol/L), total thiol (µmol/L), and disulfide (µmol/L) were measured. Disulfide/native thiol (%), disulfide/total thiol (%), and native thiol/total thiol (%) ratios were calculated. RESULTS: No significant difference was observed in thiol values in maternal blood (p>0.05). There was a significant difference between the groups in terms of native/total thiol (p=0.017), disulfide/total thiol (%) (p=0.018), and disulfide/native thiol (%) (p=0.018) in cord blood. CONCLUSION: In the literature, evidence concerning the impact of the mode of delivery on the level of neonatal and maternal oxidative stress is inconsistent. It is not clear whether parturition accompanied by pain, as in spontaneous vaginal delivery, poses more oxidative stress than a planned operative delivery. Prospective studies in larger cohorts are needed to better understand the impact of oxidative stress on pregnant women and neonates.
Assuntos
Cesárea , Parto Obstétrico , Dissulfetos , Sangue Fetal , Estresse Oxidativo , Compostos de Sulfidrila , Humanos , Gravidez , Feminino , Compostos de Sulfidrila/sangue , Dissulfetos/sangue , Estudos Prospectivos , Estresse Oxidativo/fisiologia , Adulto , Parto Obstétrico/métodos , Sangue Fetal/química , Adulto Jovem , Valores de Referência , Trabalho de Parto/sangue , Trabalho de Parto/fisiologiaRESUMO
BACKGROUND: Many free radicals result in an inflammatory process due to complications caused by gallstones. These free radicals are inactivated by various reactions and participate in different reactions. Molecules are oxidants and antioxidants that take an active role in almost every event that takes place in the body. AIMS: To analyse the changes in total antioxidant level (TAL) and total oxidant level (TOL) in the follow-up of patients hospitalized for cholelithiasis or its complications, showing the active oxidative stress, and to test the usability of these parameters in the evaluation of treatment success. METHODS: Forty-five patients took part in the study. Blood samples were taken twice, previous to surgery and 6 hours after surgery. Tissue samples were also obtained from patients who were operated. Then, the samples were sent to a laboratory to measure the total oxidant and antioxidant status of patients. RESULTS: The median for the TAL_before (pre-operation or hospitalization in non-operational) variable was 2.40 (interquartile range - IQR=0.50), and the median for the TAL_after variable was 2.20 (IQR=0.33). The median of the tissue-derived TAL variable was 0.32 (IQR=0.13), and the median of the TOL variable was 0.43 (IQR=0.52). The median value of the TAL_before variable for men was 2.50 (IQR=0.50), while the median value for the TAL_before variable for women was 2.30 (IQR=0.50). TAL_before variable values did not show a statistically significant difference according to gender (Z=1.446; p=0.154, p>0.05). Similarly, the median values of TOL_before variable by gender were similar (Z=0.614; p=0.545, p>0.05). CONCLUSIONS: Cholelithiasis and its complications cause many inflammatory responses, ending with free radical formation. During follow-up, its level decreases due to consumption or success of the treatment.
Assuntos
Antioxidantes , Oxidantes , Humanos , Feminino , Masculino , Antioxidantes/análise , Antioxidantes/metabolismo , Pessoa de Meia-Idade , Oxidantes/sangue , Cálculos Biliares/sangue , Cálculos Biliares/cirurgia , Adulto , Idoso , Estresse Oxidativo/fisiologiaRESUMO
BACKGROUND: Excitotoxicity is a process in which NADPH oxidase-2 (NOX-2) plays a pivotal role in the generation of reactive oxygen species (ROS). Oxidative stress influences the expression of Aquaporin 4 (AQP4), a water channel implicated in blood-brain barrier (BBB) permeability and edema formation. The endocannabinoid system is widely distributed in the brain, particularly through the cannabinoid receptor type 1 (CB1) and type 2 (CB2), which have been shown to have a neuroprotective function in brain injury. Given the significant involvement of NOX-2 in ROS production during excitotoxicity, our research aims to assess the participation of NOX-2 in the neuroprotective effect of the cannabinoid receptor agonist WIN55,212-2 against glutamate-induced excitotoxicity damage in the striatum using in vivo model. METHODS: Wild-type mice (C57BL/6) and NOX-2 KO (gp91Cybbtm1Din/J) were stereotactically injected in the striatum with monosodium glutamate or vehicle. Subsequently, a group of mice was administered an intraperitoneal dose of WIN55,212-2, AM251, or AM251/WIN55,212-2 following the intracerebral injection. Motor activity was assessed, and the lesion was examined through histological sections stained with cresyl violet. Additionally, brain water content and Evans blue assay were conducted. The activity of NOX was quantified, and the protein expression of CB1, gp91phox, AQP4, Iba-1, TNF-α, and NF-κB was analyzed using Western blot. Furthermore, ROS formation was measured through the DHE assay. RESULTS: The activation of the endocannabinoid receptors demonstrated a neuroprotective response during excitotoxicity, meditated by NOX-2. The reduction in ROS production led to a decrease in neuroinflammation, and AQP4 expression, resulting in reduced edema formation, and BBB permeability. CONCLUSIONS: During excitotoxic damage, WIN55,212-2 inhibits NOX-2-induced ROS production, reducing brain injury.
Assuntos
Benzoxazinas , Ácido Glutâmico , Camundongos Endogâmicos C57BL , Morfolinas , NADPH Oxidase 2 , Naftalenos , Estresse Oxidativo , Receptor CB1 de Canabinoide , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , NADPH Oxidase 2/metabolismo , Benzoxazinas/farmacologia , Morfolinas/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/toxicidade , Naftalenos/farmacologia , Camundongos , Masculino , Camundongos Knockout , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Espécies Reativas de Oxigênio/metabolismo , Aquaporina 4/metabolismo , Edema Encefálico/metabolismo , Edema Encefálico/prevenção & controleRESUMO
BACKGROUND: Depression and memory loss are prevalent neurodegenerative disorders, with diabetic patients facing an elevated risk of brain dysfunction. Methylglyoxal (MGO) formation, which is heightened in diabetes owing to hyperglycemia and gut dysbiosis, may serve as a critical link between diabetes and brain diseases. Despite the high prevalence of MGO, the precise mechanisms underlying MGO-induced depression and memory loss remain unclear. RESULTS: We investigated the effect of MGO stress on depression like-behavior and memory loss to elucidate the potential interplay between MGO-induced tryptophan (Trp) metabolism impairment and oxidative stress in the brain. It demonstrates that MGO induces depression-like behavior in mice, as confirmed by the OFT, TST, FST, SPT, and EPM behavioral tests. MGO led to the depletion of Trp and related neurotransmitters as 5-HT, EPI, and DA in the mouse brain. Additionally, MGO reduced the cell count in the DG, CA1, and CA3 hippocampal regions and modulated TPH2 levels in the brain. Notably, co-treatment with MGO and Trp mirrored the effects observed after Trp-null treatment in neurons, including reduced TPH1 and TPH2 levels and inhibition of neuronal outgrowth. Furthermore, MGO significantly altered the expression of key proteins associated with neurodegeneration, such as p-Tau, p-GSK-3ß, APP, oAß, BDNF, NGF, and p-TrkB. Concurrently, MGO activated MAPKs through ROS induction, triggering a redox imbalance by downregulating Nrf-2, Ho-1, TXNRD1, Trx, Sirt-3, and Sirt-5 expression levels, NAD+, and CAT activity in the mouse brain. This led to an accelerated neuroinflammatory response, as evidenced by increased expression of Iba-1, p-NF-κB, and the secretion of IL-6 and TNF-α. Importantly, Trp treatment ameliorated MGO-induced depression like-behavior and memory loss in mice and markedly mitigated increased expression of p-Tau, APP, p-ERK1/2, p-pJNK, and p-NF-κB in the brain. Likewise, Trp treatment also induced the expression of MGO detoxifying factors GLO-I and GLO-II and CAT activity, suggesting the induction of an antioxidant system and reduced inflammation by inhibiting IL-6 and TNF-α secretion. CONCLUSIONS: Our data revealed that MGO-induced depression like-behavior and memory deficits resulted from disturbances in Trp, 5-HT, BDNF, and NGF levels, increased p-Tau and APP expression, neuroinflammation, and impaired redox status (Nrf-2/Ho-1/TXNRD1/Sirt3/5) in the brain.
Assuntos
Depressão , Modelos Animais de Doenças , Transtornos da Memória , Estresse Oxidativo , Aldeído Pirúvico , Triptofano , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Aldeído Pirúvico/metabolismo , Transtornos da Memória/metabolismo , Transtornos da Memória/induzido quimicamente , Depressão/metabolismo , Triptofano/metabolismo , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/induzido quimicamente , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
Alcohol Use Disorder (AUD) is a highly prevalent medical condition characterized by impaired control over alcohol consumption, despite negative consequences on the individual's daily life and health. There is increasing evidence suggesting that chronic alcohol intake, like other addictive drugs, induces neuroinflammation and oxidative stress, disrupting glutamate homeostasis in the main brain areas related to drug addiction. This review explores the potential application of mesenchymal stem cells (MSCs)-based therapy for the treatment of AUD. MSCs secrete a broad array of anti-inflammatory and antioxidant molecules, thus, the administration of MSCs, or their secretome, could reduce neuroinflammation and oxidative stress in the brain. These effects correlate with an increase in the expression of the main glutamate transporter, GLT1, which, through the normalization of the extracellular glutamate levels, could mediate the inhibitory effect of MSCs' secretome on chronic alcohol consumption, thus highlighting GLT1 as a central target to reduce chronic alcohol consumption.
Assuntos
Alcoolismo , Transplante de Células-Tronco Mesenquimais , Humanos , Alcoolismo/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Células-Tronco Mesenquimais , Estresse Oxidativo/fisiologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Postoperative cognitive dysfunction (POCD), a complication following procedures such as orthopedic surgery, is associated with a worsened prognosis, especially in the elderly population. Several mechanisms have been proposed for communication between the immune system and the brain after surgery. In an experimental tibial fracture (TF) model, we aimed to understand the role of the NLR family pyrin domain containing 3 (NLRP3) on oxidative stress and mitochondrial dysfunction as mechanisms underlying POCD in aged and adult rats. Adult or aged male Wistar rats were subjected to the TF model and received intracerebroventricular saline or MCC950 (140 ng/kg), a specific small-molecule inhibitor that selectively blocks activation of the NLRP3 inflammasome. We followed the control (sham) and TF groups treated with MCC950 or saline for seven days to determine cognitive function and survival. The prefrontal cortex and hippocampus were isolated for NLRP3 evaluation, cytokine analysis, oxidative stress measurements, myeloperoxidase activity, nitric oxide formation, mitochondrial respiratory chain enzymes, and succinate dehydrogenase (SDH) activity. Seven days after TF induction, NLRP3 levels increased in the hippocampus and prefrontal cortex in both ages, showed an enhancement in aged rats compared to adults, and experienced a reversal with MCC950 administration. The administration of MCC950 restored memory, IL-1ß and IL-10 levels, nitrite/nitrate, lipid peroxidation in the hippocampus and prefrontal cortex, and preserved catalase activity in the prefrontal cortex in aged rats. At the same age, the complex I activity alteration in both regions and complex II, IV, and SDH in the prefrontal cortex were reversed. In conclusion, NLRP3 activation contributes to POCD development because it is intrinsically involved in mitochondrial dysfunction and oxidative stress after orthopedic surgery in aged rats.
Assuntos
Mitocôndrias , Proteína 3 que Contém Domínio de Pirina da Família NLR , Estresse Oxidativo , Complicações Cognitivas Pós-Operatórias , Ratos Wistar , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Masculino , Ratos , Complicações Cognitivas Pós-Operatórias/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Envelhecimento/metabolismo , Indenos/farmacologia , Sulfonamidas/farmacologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Furanos/farmacologia , Sulfonas/farmacologiaRESUMO
BACKGROUND: Although important information concerning COVID-19 vaccination is available, the effects of the CoronaVac and ChadOx-1 vaccines on immunity and the redox balance in the upper airway mucosa of the aged population are not fully understood. Therefore, the aim of this study was to investigate the impacts of two doses of the CoronaVac or ChadOx-1 vaccine on immune/inflammatory responses and oxidative stress in the airway mucosa of older adults. METHODS: Seventy-six older adults of both sexes, with a mean age of 75.1 ± 6.4 years, were separated according to vaccination status into the CoronaVac (n = 52) and ChadOx-1 (n = 24) groups. Saliva samples were collected before (pre) and 30 days after (post) the administration of the second dose of the CoronaVac or ChadOx-1 vaccine to assess the levels of antibodies (sIgA and IgG), antimicrobial peptides, cytokines, and oxidant/antioxidant agents. RESULTS: The immunogenicity in the ChadOx-1 group was 37.5% for sIgA and 25% for IgG, while that in the CoronaVac group was 18.9% for sIgA and 13.2% for IgG. Intergroup analysis revealed that (1) lower levels of IFN-α, IFN-γ, and IL-10 and a greater IFN-γ/IL-10 ratio, in addition to a greater IL-6/IL-10 ratio, were found in both the pre- and postvaccination periods, and (2) lower levels of total sIgA, IL-12p70, IL-17A, TNF-α, and the IL-12p70/IL-10 ratio, in addition to higher levels of specific sIgA for SARS-CoV-2 antigens and lysozyme, were observed only in the postvaccination period in the ChadOx-1 group than in the CoronaVac group. Intragroup analysis revealed (1) a significant increase in the salivary levels of total peroxides in the postvaccination period compared to those in the prevaccination period in both volunteer groups; (2) a decrease in the levels of lysozyme and the ratio between total antioxidant capacity (TAC) and total peroxides in the postvaccination period in the CoronaVac group compared with those in the prevaccination period; and (3) decreases in the TNF-α, IL-6, and IL-12p70 levels, and the IL-12p70/IL-10 ratio in the ChadoX-1 group, as well as a higher lactoferrin concentration in the postvaccination period than in the prevaccination period. Several positive and negative correlations between the parameters assessed here were found. CONCLUSIONS: In general, the ChadOx-1 group exhibited improvements in both immune/inflammatory responses and redox balance and greater immunogenicity than did the CoronaVac group.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Estresse Oxidativo , Saliva , Humanos , Feminino , Masculino , Idoso , Estresse Oxidativo/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Saliva/metabolismo , Saliva/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Idoso de 80 Anos ou mais , Citocinas/metabolismo , SARS-CoV-2/imunologia , Imunoglobulina G , Inflamação/metabolismo , Vacinas de Produtos InativadosRESUMO
Objective: Sex differences in lipid metabolism associated with prevalent small dense (S-) low-density lipoprotein (LDL) cholesterol particles are not elucidated. An LDL to apolipoprotein B (ApoB) ratio < 1.2 can estimate how prevalent S-LDL particles are and, thus, reflect cardiovascular risk. The aim of this study was to evaluate the sex distribution of LDL/ApoB ratio among patients with type 2 diabetes (DM) and to assess, in both sexes, the correlations between key lipid parameters and LDL/ApoB < 1.2. Subjects and methods: The study included 190 Caucasian participants (mean age 51.8 ± 6.4 years) with DM (DM group) or without DM (control group) divided into subgroups according to sex. The participants were examined for levels of several lipid parameters, selected lipid-related oxidative stress markers, and estimated S-LDL prevalence. Results: An LDL/ApoB < 1.2 (p < 0.05) was observed in 67% of male and female patients with DM. Although triglyceride levels did not differ between men and women, women had higher levels of total cholesterol (p < 0.05) and LDL cholesterol (p < 0.01) than men. Among women with LDL/ApoB < 1.2, strong correlations were observed between values of lipid hydroperoxides (LOOH) and atherogenic index of plasma (p < 0.005) and between levels of triglycerides and LOOH (p < 0.005) and ApoB (p < 0.0001). Conclusions: The findings indicate that women with LDL/ApoB < 1.2 tend to have a higher cardiovascular risk than men. Additionally, LDL/ApoB < 1.2 can be a surrogate marker for estimating the S-LDL prevalence in individuals with potentially increased cardiovascular risk.
Assuntos
Doenças Cardiovasculares , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Fatores de Risco de Doenças Cardíacas , Humanos , Diabetes Mellitus Tipo 2/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Fatores Sexuais , Adulto , Apolipoproteínas B/sangue , Biomarcadores/sangue , Triglicerídeos/sangue , Fatores de Risco , Estresse Oxidativo/fisiologia , Lipídeos/sangueRESUMO
Pulmonary arterial hypertension (PAH) is a disease that affects millions of people worldwide. Besides the effects on the lungs and heart, PAH can affect other organs, including the liver, kidneys, brain, glands, and testis. This study aimed to evaluate the impact of PAH and physical resistance training (RT), a complementary treatment for hypertension, on epididymis morphology and function and sperm parameters. Wistar rats were divided into four experimental groups (n = 8/ group): sedentary control, sedentary PAH, RT control, and RT + PAH. PAH was induced using monocrotaline injections on Day 1 and 7 of the experiment. Sixteen rats from RT groups underwent RT training for 30 days, while rats from sedentary groups did not exercise. The epididymis was processed and analyzed using microscopic, biochemical, and functional approaches. Sperm were harvested from the cauda epididymis and evaluated for morphology and motility. Our results showed that PAH compromised the epididymis antioxidant defense system and reduced NO levels, leading to an imbalance in the organ's mineral content. These alterations affected the epididymis morphology and reduced the sperm transit time in the proximal epididymis, resulting in an increase in abnormal sperm morphology in the cauda region. Unfortunately, RT was not a good therapy against the PAH effect on the epididymis. PAH negatively affected epididymis functions with consequences to male gametes. Dysfunctions in the post-testicular environment may lead to male infertility due to the disturbance of spermatozoa fecundity.
Assuntos
Epididimo , Condicionamento Físico Animal , Ratos Wistar , Espermatozoides , Animais , Masculino , Epididimo/metabolismo , Epididimo/patologia , Ratos , Condicionamento Físico Animal/fisiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/patologia , Motilidade dos Espermatozoides/fisiologia , Comportamento Sedentário , Estresse Oxidativo/fisiologiaRESUMO
Data about the impacts of hemodialysis on antioxidant status and markers of oxidative stress are controversial, probably due to the use of different methodological approaches. The aim of this study was to assess the changes in the oxidative damage markers and antioxidant enzymes, and the serum antioxidant capacity by using in vitro model systems of free radical generation before and after one hemodialysis session. Blood samples were collected from 40 patients with kidney failure before and after hemodialysis. In pre- and post-hemodialysis serum samples, concentrations of biomarkers of oxidative damage and the activities of antioxidant enzymes were measured, as well as the in vitro antioxidant potential. The high concentrations of oxidative stress markers in serum of kidney failure patients were decreased after one hemodialysis session. In pre-hemodialysis, low activities of antioxidant enzymes were observed, including paraoxonase-1, however paraoxonase-1 activity was partially recovered after hemodialysis. Crocin bleaching and radical scavenging assays showed that serum antioxidant potential was decreased after hemodialysis. Although one hemodialysis session increased paraoxonase-1 activity and decreased oxidative stress markers, it caused a decrease in the serum antioxidant potential. Future research is needed to prospect strategies to mitigate the impacts of oxidative stress in the scenario of hemodialysis repetitions.
Assuntos
Antioxidantes , Biomarcadores , Estresse Oxidativo , Diálise Renal , Humanos , Estresse Oxidativo/fisiologia , Diálise Renal/efeitos adversos , Biomarcadores/sangue , Masculino , Antioxidantes/metabolismo , Antioxidantes/análise , Feminino , Pessoa de Meia-Idade , Arildialquilfosfatase/sangue , Adulto , Insuficiência Renal/sangue , Insuficiência Renal/terapia , Falência Renal Crônica/terapia , Falência Renal Crônica/sangue , IdosoRESUMO
Oxidative stress (OS) is a ubiquitous process for protecting against microorganisms' challenges. This review maps the most used methods for obtaining samples and analysing reactive oxygen species levels in apical periodontitis, following the PRISMA Extension for Scoping Reviews and is registered in Open Science Framework ([https://doi.org/10.17605/OSF.IO/D5U76]). A systematic search was conducted in electronic databases MEDLINE (PubMed), Embase, Scopus, Web of Science, LILACS, SciElo, OATD and DANS up to 17 July 2023. A total of 18 studies were included, with periapical tissue being the most common sample. Twenty-eight different oxidative stress markers were identified, with inducible nitric oxide synthase being the most prevalent. The use of diverse biomarkers for oxidative stress assessment lacks specificity in identifying particular OS species for evaluating apical periodontitis and potential systemic effects. Studies are necessary to compare results obtained from less invasive methods (such as saliva and crevicular fluid) with those from periapical lesion samples.
Assuntos
Bibliometria , Biomarcadores , Estresse Oxidativo , Periodontite Periapical , Humanos , Biomarcadores/análise , Estresse Oxidativo/fisiologia , Periodontite Periapical/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/análiseRESUMO
Pentylenetetrazole (PTZ), a tetrazole derivative, is commonly used as a chemical agent to induce neurological disorders and replicate the characteristics of human epileptic seizures in animal models. This review offers a comprehensive analysis of the behavioral, neurophysiological, and neurochemical changes induced by PTZ. The epileptogenic and neurotoxic mechanisms of PTZ are associated with an imbalance between the GABAergic and glutamatergic systems. At doses exceeding 60 mg/kg, PTZ exerts its epileptic effects by non-competitively antagonizing GABAA receptors and activating NMDA receptors, resulting in an increased influx of cations such as Na+ and Ca2+. Additionally, PTZ promotes oxidative stress, microglial activation, and the synthesis of pro-inflammatory mediators, all of which are features characteristic of glutamatergic excitotoxicity. These mechanisms ultimately lead to epileptic seizures and neuronal cell death, which depend on the dosage and method of administration. The behavioral, electroencephalographic, and histological changes associated with PTZ further establish it as a valuable preclinical model for the study of epileptic seizures, owing to its simplicity, cost-effectiveness, and reproducibility.
Assuntos
Pentilenotetrazol , Pentilenotetrazol/toxicidade , Animais , Humanos , Convulsões/induzido quimicamente , Convulsões/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Epilepsia/induzido quimicamente , Convulsivantes/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologiaRESUMO
Neonatal immune activation (NIA) through exposure to lipopolysaccharide (LPS) induces adult behavioral changes in rodents that resemble symptoms of developmental disorders, such as autism spectrum disorder. The neonatal timing of LPS exposure appears to play a crucial role in determining the nature and extent of long-term changes. This study aims to explore whether a 3-day LPS-NIA triggers sex- and age-related changes in gut function, potentially linking LPS-NIA to gastrointestinal dysfunction. Male and female Swiss mice received intraperitoneal injections of LPS or saline on postnatal days (PN) 3, 5, and 7. At PN35 (juvenile) and PN70 (adult), gut inflammation and oxidative stress were evaluated in addition to assessments of working memory, depressive-like symptoms, sociability, and repetitive behavior. Gut examination showed elevated C-X-C motif chemokine receptor 3 (CXCR3) in LPS-NIA mice, while MyD88 and Zonulin expressions were significantly higher only in adult LPS-NIA females. Interleukin (IL)-23 expression increased in juvenile and adult male and juvenile female LPS-NIA mice. Oxidative changes included decreased duodenal reduced glutathione (GSH) in juvenile females and ileal GSH in adult females exposed to LPS-NIA. Regarding behavioral alterations, adult LPS-NIA females exhibited depressive-like behavior. Working memory deficits were observed across all LPS-NIA groups. Only juvenile LPS-NIA females increased grooming, while rearing was higher in adult LPS-NIA mice of both sexes. The findings imply that LPS-NIA impacts intestinal barrier function and causes gut inflammatory alterations that are sex- and age-specific. These findings pave the way for exploring potential mechanisms that could contribute to LPS-induced gastrointestinal disturbances among individuals with ASD.
Assuntos
Animais Recém-Nascidos , Lipopolissacarídeos , Caracteres Sexuais , Animais , Lipopolissacarídeos/toxicidade , Feminino , Camundongos , Masculino , Fatores Etários , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Envelhecimento/imunologia , Envelhecimento/fisiologiaRESUMO
Aging is a major risk factor for cognitive deficits, impaired locomotion, and gait disorders. Although oxidative stress and circadian disruption are involved in both normal aging and the pathogenesis of age-associated diseases, just a very few studies explore the consequences of aging on circadian rhythms in the cerebellum. Here, we investigated age-dependent changes in the circadian organization of the molecular clock, antioxidant defenses and synaptic plasticity-related factors, in the rat cerebellum, and discussed the impact of that altered temporal organization on the cognitive function of this brain area. Particularly, we examined the circadian patterns of Brain and muscle ARNT-like 1 (BMAL1) protein levels, Glutathione peroxidase 4 (GPx4) gene expression, GPx and Catalase (CAT) enzymes activity, reduced glutathione (GSH) levels, and the Brain-derived neurotrophic factor (Bdnf) and its Tyrosine kinase receptor B (TrkB) circadian expression. Endogenously-driven circadian rhythms of BMAL1, GPx4, CAT, GSH, and Bdnf/TrkB factors, were observed in the young rat cerebellum. The rhythms' acrophases show a circadian organization that might be crucial for the daily cerebellar-dependent cognitive functions. Notably, aging disrupted circadian rhythms and the temporal organization of BMAL1, antioxidant defenses, and cognitive Bdnf/TrkB gene expression. Increased oxidative stress and disruption of clock-controlled rhythms during aging, might precede and cause the loss of circadian organization in the aged cerebellum. We expect our results highlight circadian rhythms of the studied factors as new targets for the treatment of age-dependent cerebellar disorders.
Assuntos
Fatores de Transcrição ARNTL , Envelhecimento , Antioxidantes , Fator Neurotrófico Derivado do Encéfalo , Catalase , Cerebelo , Ritmo Circadiano , Ratos Wistar , Animais , Cerebelo/metabolismo , Envelhecimento/metabolismo , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Ritmo Circadiano/fisiologia , Antioxidantes/metabolismo , Catalase/metabolismo , Catalase/genética , Ratos , Cognição/fisiologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Receptor trkB/metabolismo , Receptor trkB/genética , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/genética , Estresse Oxidativo/fisiologia , Doenças Cerebelares/metabolismo , Doenças Cerebelares/genética , Glutationa/metabolismo , Expressão GênicaRESUMO
Complex regional pain syndrome (CRPS) presents as a persistent and distressing pain condition often stemming from limb trauma or ischemia, manifesting as either CRPS-I (without initial nerve injury) or CRPS-II (accompanied by nerve injury). Despite its prevalence and significant impact on functionality and emotional well-being, standard treatments for CRPS remain elusive. The multifaceted nature of CRPS complicates the identification of its underlying mechanisms. In efforts to elucidate these mechanisms, researchers have turned to animal models such as chronic post-ischemic pain (CPIP), which mirrors the symptoms of CRPS-I. Various mechanisms have been proposed to underlie the acute and chronic pain experienced in CRPS-I, including oxidative stress and inflammation. Traditional treatment approaches often involve antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), and opioids. However, these methods frequently fall short of providing adequate relief. Accordingly, there is a growing interest in exploring alternative treatments, such as antioxidant supplementation, anti-inflammatory agents, and non-pharmacological interventions. Future research directions should focus on optimizing treatment strategies and addressing remaining gaps in knowledge to improve patient outcomes. This review aims to delve into the pathophysiological mechanisms implicated in the CPIP model, specifically focusing on oxidative stress and inflammation, with the ultimate goal of proposing innovative therapeutic strategies for alleviating the symptoms of CRPS-I.
Assuntos
Inflamação , Estresse Oxidativo , Estresse Oxidativo/fisiologia , Humanos , Animais , Inflamação/metabolismo , Síndromes da Dor Regional Complexa/fisiopatologia , Síndromes da Dor Regional Complexa/terapia , Síndromes da Dor Regional Complexa/metabolismo , Dor Crônica/metabolismo , Isquemia/metabolismo , Modelos Animais de DoençasRESUMO
Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.
Assuntos
Lipopolissacarídeos , Transtornos da Memória , Doenças Neuroinflamatórias , Condicionamento Físico Animal , Ratos Wistar , Animais , Masculino , Lipopolissacarídeos/toxicidade , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Ratos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/induzido quimicamente , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Treinamento Resistido/métodos , Córtex Cerebral/metabolismo , Córtex Cerebral/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Receptor Muscarínico M1/metabolismoRESUMO
OBJECTIVE: The purpose of the present study was to examine the association of oxidative stress markers with sarcopenia in the general United States population under the age of 60. METHODS: We used the National Health and Nutrition Examination Survey data from 2011â2014 and performed Restricted Cubic Spline (RCS) plots, weighted multivariable logistic regression analysis to calculate ratio ratios and 95% Confidence Intervals, and subgroup analysis based on age, sex, hypertension, diabetes mellitus, and body mass index stratification to determine the association of markers of oxidative stress with the prevalence of sarcopenia. RESULTS: The present analysis included a total of 8,782 participants. Firstly, the RCS plots showed a roughly L-shaped curve association of total bilirubin and serum iron with a prevalence of sarcopenia. Secondly, albumin was negatively and linearly associated with the risk of sarcopenia. Finally, with the increase in gamma-glutamyl transferase, the prevalence of sarcopenia showed a trend of first rising and then declining as a result of the iron increase. CONCLUSIONS: We demonstrated a nonlinear association between markers of oxidative stress and sarcopenia. The need to focus more on levels of oxidative stress in the body could provide better prevention strategies for sarcopenia.