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Lung adenocarcinoma stands as a leading global cause of cancer-related fatalities, with current therapeutic approaches remaining unsatisfactory. Given the association between elevated oxidative markers and the aggressive nature of cancer cells (including multidrug resistance and metastatic potential) that can predict poor outcome of lung adenocarcinoma patients, any compounds that interfere with their aberrant redox biology should be rationally explored as innovative intervention strategies. This study was designed to screen potential anticancer activities within nine newly synthesized organochalcogen - compounds characterized by the presence of oxygen, sulfur, or selenium elements in their structure and exhibiting antioxidant activity - and systematically evaluated their performance against cisplatin, the cornerstone therapeutic agent for lung adenocarcinoma. Our methodology involved the establishment of optimal conditions for generating single tumor spheroids using A549 human lung adenocarcinoma cell line. The initiation interval for spheroid formation was determined to be four days in vitro (DIV), and these single spheroids demonstrated sustained growth over a period of 20 DIV. Toxic dose-response curves were subsequently performed for each compound after 24 and 48 h of incubation at the 12th DIV. Our findings reveal that at least two of the synthetic organochalcogen compounds exhibited noteworthy anticancer activity, surpassing cisplatin in key parameters such as lower LD (Lethal Dose) 50, larger drug activity area, and maximum amplitude of effect, and are promising drugs for futures studies in the treatment of lung adenocarcinomas. Physicochemical descriptors and prediction ADME (absorption, distribution, metabolism, and excretion) parameters of selected compounds were obtained using SwissADME computational tool; Molinspiration server was used to calculate a biological activity score, and possible molecule targets were evaluated by prediction with the SwissTargetPrediction server. This research not only sheds light on novel avenues for therapeutic exploration but also underscores the potential of synthetic organochalcogen compounds as agents with superior efficacy compared to established treatments.
Assuntos
Adenocarcinoma de Pulmão , Antineoplásicos , Calcogênios , Cisplatino , Neoplasias Pulmonares , Esferoides Celulares , Humanos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Calcogênios/química , Calcogênios/farmacologia , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Células A549 , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Sobrevivência Celular/efeitos dos fármacosRESUMO
The aim of this study was to investigate the antiglioma effect of Cecropia pachystachya Trécul (CEC) leaves extract against C6 and U87 glioblastoma (GB) cells and in a rat preclinical GB model. The CEC extract reduced in vitro cell viability and biomass. In vivo, the extract decreased the tumor volume approximately 62%, without inducing systemic toxicity. The deficit in locomotion and memory and an anxiolytic-like behaviors induced in the GB model were minimized by CEC. The extract decreased the levels of reactive oxygen species, nitrites and thiobarbituric acid reactive substances and increased the activity of antioxidant enzymes in platelets, sera and brains of GB animals. The activity of NTPDases, 5'-nucleotidase and adenosine deaminase (ADA) was evaluated in lymphocytes, platelets and serum. In platelets, ATP and AMP hydrolysis was reduced and hydrolysis of ADP and the activity of ADA were increased in the control, while in CEC-treated animals no alteration in the hydrolysis of ADP was detected. In serum, the reduction in ATP hydrolysis was reversed by CEC. In lymphocytes, the increase in the hydrolysis of ATP, ADP and in the activity of ADA observed in GB model was altered by CEC administration. The observed increase in IL-6 and decrease in IL-10 levels in the serum of GB animals was reversed by CEC. These results demonstrate that CEC extract is a potential complementary treatment to GB, decreasing the tumor size, while modulating aspects of redox and purinergic systems.
RESUMO
Alzheimer's disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.
Assuntos
Doença de Alzheimer , Inosina , Receptores Purinérgicos , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Inosina/farmacologia , Inosina/uso terapêutico , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Doenças Neuroinflamatórias , Ratos , Ratos Wistar , Receptores Purinérgicos/metabolismo , EstreptozocinaRESUMO
Aluminum (Al) is ubiquitously present in the environment and known to be a neurotoxin for humans. The trivalent free Al anion (Al3+) can cross the blood-brain barrier (BBB), accumulate in the brain, and elicit harmful effects to the central nervous system (CNS) cells. Thus, evidence has suggested that Al increases the risk of developing neurodegenerative diseases, particularly Alzheimer's disease (AD). Purinergic signaling has been shown to play a role in several neurological conditions as it can modulate the functioning of several cell types, such as microglial cells, the main resident immune cells of the CNS. However, Al effects on microglial cells and the role of the purinergic system remain elusive. Based on this background, this study is aimed at assessing the modulation of Al on purinergic system parameters of microglial cells. An in vitro study was performed using brain microglial cells exposed to Al chloride (AlCl3) and lipopolysaccharide (LPS) for 96 h. The uptake of Al, metabolism of nucleotides (ATP, ADP, and AMP) and nucleoside (adenosine), and the gene expression and protein density of purinoceptors were investigated. The results showed that both Al and LPS increased the breakdown of adenosine, whereas they decreased nucleotide hydrolysis. Furthermore, the findings revealed that both Al and LPS triggered an increase in gene expression and protein density of P2X7R and A2AR receptors, whereas reduced the A1R receptor expression and density. Taken together, the results showed that Al and LPS altered the setup of the purinergic system of microglial cells. Thus, this study provides new insights into the involvement of the purinergic system in the mechanisms underlying Al toxicity in microglial cells.
Assuntos
Alumínio/efeitos adversos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Receptores Purinérgicos/metabolismo , Animais , Biomarcadores , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/metabolismo , Linhagem Celular , Células Cultivadas , Imunofluorescência , Expressão Gênica , Humanos , Lipopolissacarídeos/imunologia , Camundongos , Microglia/imunologia , Receptores Purinérgicos/genéticaRESUMO
Novel coronavirus disease 2019 (COVID-19) causes pulmonary and cardiovascular disorders and has become a worldwide emergency. Myocardial injury can be caused by direct or indirect damage, particularly mediated by a cytokine storm, a disordered immune response that can cause myocarditis, abnormal coagulation, arrhythmia, acute coronary syndrome, and myocardial infarction. The present review focuses on the mechanisms of this viral infection, cardiac biomarkers, consequences, and the possible therapeutic role of purinergic and adenosinergic signalling systems. In particular, we focus on the interaction of the extracellular nucleotide adenosine triphosphate (ATP) with its receptors P2X1, P2X4, P2X7, P2Y1, and P2Y2 and of adenosine (Ado) with A2A and A3 receptors, as well as their roles in host immune responses. We suggest that receptors of purinergic signalling could be ideal candidates for pharmacological targeting to protect against myocardial injury caused by a cytokine storm in COVID-19, in order to reduce systemic inflammatory damage to cells and tissues, preventing the progression of the disease by modulating the immune response and improving patient quality of life.
Assuntos
Trifosfato de Adenosina/metabolismo , COVID-19/imunologia , Doenças Cardiovasculares/virologia , Receptores Purinérgicos/metabolismo , SARS-CoV-2 , Agonistas do Receptor A2 de Adenosina/farmacologia , COVID-19/metabolismo , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Citocinas/metabolismo , Humanos , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/virologia , Pandemias , Antagonistas Purinérgicos/farmacologia , Receptor A2A de Adenosina/metabolismo , Receptor A3 de Adenosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Tratamento Farmacológico da COVID-19RESUMO
This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of lymphocytes, IL-6 and IL-10 levels and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) activity in rat lymphocytes. The animals were divided into groups: control, caffeine 4 mg/kg, caffeine 8 mg/kg, HIIT, HIIT plus caffeine 4 mg/kg and HIIT plus caffeine 8 mg/kg. The rats were trained three times a week for 6 weeks for a total workload 23% of body weight at the end of the experiment. Caffeine was administered orally 30 min before the training session. When lymphocytes were stimulated with phytohaemagglutinin no changes were observed in proliferative response between trained and sedentary animals; however, when caffeine was associated with HIIT an increase in T lymphocyte proliferation and in the sensitivity of lymphocytes to glucocorticoids occurred. ATP and ADP hydrolysis was decreased in the lymphocytes of the animals only trained and caffeine treatment prevented alterations in ATP hydrolysis. HIIT caused an increase in the ADA and AChE activity in lymphocytes and this effect was more pronounced in rats trained and supplemented with caffeine. The level of IL-6 was increased while the level of IL-10 was decreased in trained animals (HIIT) and caffeine was capable of preventing this exercise effect. Our findings suggest that caffeine ingestion attenuates, as least in part, the immune and inflammatory alterations following a prolonged HIIT protocol.
Assuntos
Cafeína/farmacologia , Citocinas/metabolismo , Linfócitos/metabolismo , Condicionamento Físico Animal , Receptores Colinérgicos/metabolismo , Receptores Purinérgicos/metabolismo , Transdução de Sinais , Acetilcolinesterase/metabolismo , Adenosina/metabolismo , Adenosina Desaminase/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Glucocorticoides/farmacologia , Hidrólise , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Masculino , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
Evidences show that purinergic signaling is involved in processes associated with health and disease, including noncommunicable, neurological, and degenerative diseases. These diseases strike from children to elderly and are generally characterized by progressive deterioration of cells, eventually leading to tissue or organ degeneration. These pathological conditions can be associated with disturbance in the signaling mediated by nucleotides and nucleosides of adenine, in expression or activity of extracellular ectonucleotidases and in activation of P2X and P2Y receptors. Among the best known of these diseases are atherosclerosis, hypertension, cancer, epilepsy, Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The currently available treatments present limited effectiveness and are mostly palliative. This review aims to present the role of purinergic signaling highlighting the ectonucleotidases E-NTPDase, E-NPP, E-5'-nucleotidase, and adenosine deaminase in noncommunicable, neurological, and degenerative diseases associated with the cardiovascular and central nervous systems and cancer. In conclusion, changes in the activity of ectonucleotidases were verified in all reviewed diseases. Although the role of ectonucleotidases still remains to be further investigated, evidences reviewed here can contribute to a better understanding of the molecular mechanisms of highly complex diseases, which majorly impact on patients' quality of life.
Assuntos
Doenças Cardiovasculares/enzimologia , Neoplasias/enzimologia , Doenças Neurodegenerativas/enzimologia , Nucleotidases/metabolismo , Receptores Purinérgicos/metabolismo , Animais , Humanos , Doenças não Transmissíveis , Qualidade de Vida , Transdução de SinaisRESUMO
Anthocyanins (ANT) are polyphenolic flavonoids with antioxidant and neuroprotective properties. This study evaluated the effect of ANT treatment on cognitive performance and neurochemical parameters in an experimental model of sporadic dementia of Alzheimer's type (SDAT). Adult male rats were divided into four groups: control (1 ml/kg saline, once daily, by gavage), ANT (200 mg/kg, once daily, by gavage), streptozotocin (STZ, 3 mg/kg) and STZ plus ANT. STZ was administered via bilateral intracerebroventricular (ICV) injection (5 µl). ANT were administered after ICV injection for 25 days. Cognitive deficits (short-term memory and spatial memory), oxidative stress parameters, and acetylcholinesterase (AChE) and Na+-K+-ATPase activity in the cerebral cortex and hippocampus were evaluated. ANT treatment protected against the worsening of memory in STZ-induced SDAT. STZ promoted an increase in AChE and Na+-K+-ATPase total and isoform activity in both structures; ANT restored this change. STZ administration induced an increase in lipid peroxidation and decrease in the level of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the cerebral cortex; ANT significantly attenuated these effects. In the hippocampus, an increase in reactive oxygen species (ROS), nitrite and lipid peroxidation levels, and SOD activity and a decrease in CAT and GPx activity were seen after STZ injection. ANT protected against the changes in ROS and antioxidant enzyme levels. In conclusion, the present study showed that treatment with ANT attenuated memory deficits, protected against oxidative damage in the brain, and restored AChE and ion pump activity in an STZ-induced SDAT in rats.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Antocianinas/farmacologia , Bombas de Íon/metabolismo , Transtornos da Memória/tratamento farmacológico , Estresse Oxidativo , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Animais , Antioxidantes/uso terapêutico , Encéfalo/metabolismo , Catalase/metabolismo , Córtex Cerebral/metabolismo , Cognição , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Infusões Intraventriculares , Peroxidação de Lipídeos , Masculino , Aprendizagem em Labirinto , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Wistar , Estreptozocina/efeitos adversos , Compostos de Sulfidrila , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND AND PURPOSE: Postoperative pain is one of the most common manifestations of acute pain and is an important problem faced by patients after surgery. Moreover, neuronal trauma or chemotherapeutic treatment often causes neuropathic pain, which induces disabling and distressing symptoms. At present, treatments of both painful conditions are inadequate. α-Spinasterol, which is well characterized as a transient receptor potential vanilloid 1 antagonist, has anti-inflammatory, antioxidant and antinociceptive effects. Therefore, we investigated its antinociceptive potential on postoperative and neuropathic pain, as well as its effect on COX-1 and COX-2 activities. EXPERIMENTAL APPROACH: Nociceptive responses in a postoperative pain model (surgical incision-induced) or different neuropathic pain models (trauma or chemotherapy-induced) were investigated in mice. KEY RESULTS: Oral administration of α-spinasterol reduced postoperative pain, when given as a pre- (0.5 h before incision) or post-treatment (0.5 h after incision), and reduced cell infiltration in the injured tissue. α-Spinasterol also reduced the mechanical allodynia induced by partial sciatic nerve ligation and the mechanical and cold allodynia induced by paclitaxel. Moreover, α-spinasterol inhibited COX-1 and COX-2 enzyme activities without altering the body temperature of animals. Importantly, α-spinasterol did not alter spontaneous or forced locomotor activity. Furthermore, it did not cause gastric damage or liver and kidney changes, nor did it alter cell viability in the cerebral cortex and spinal cord slices of mice. CONCLUSION AND IMPLICATIONS: α-Spinasterol is an effective and safe COX inhibitor with antinociceptive effects in postoperative and neuropathic pain models. Therefore, it is an interesting prototype for the development of novel analgesic drugs.
Assuntos
Neuralgia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Estigmasterol/análogos & derivados , Dor Aguda/tratamento farmacológico , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/toxicidade , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/toxicidade , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Estigmasterol/administração & dosagem , Estigmasterol/farmacologia , Estigmasterol/toxicidade , Canais de Cátion TRPV/antagonistas & inibidores , Fatores de TempoRESUMO
Diabetes is associated with long-term complications in the brain and reduced cognitive ability. Vitamin D3 (VD3 ) appears to be involved in the amelioration of hyperglycaemia in streptozotocin (STZ)-induced diabetic rats. Our aim was to analyse the potential of VD3 in avoiding brain damage through evaluation of acetylcholinesterase (AChE), Na(+) K(+) -adenosine triphosphatase (ATPase) and delta aminolevulinate dehydratase (δ-ALA-D) activities and thiobarbituric acid reactive substance (TBARS) levels from cerebral cortex, as well as memory in STZ-induced diabetic rats. Animals were divided into eight groups (n = 5): control/saline, control/metformin (Metf), control/VD3 , control/Metf + VD3 , diabetic/saline, diabetic/Metf, diabetic/VD3 and diabetic/Metf + VD3 . Thirty days after treatment, animals were submitted to contextual fear-conditioning and open-field behavioural tests, after which they were sacrificed and the cerebral cortex was dissected. Our results demonstrate a significant memory deficit, an increase in AChE activity and TBARS levels and a decrease in δ-ALA-D and Na(+) K(+) -ATPase activities in diabetic rats when compared with the controls. Treatment of diabetic rats with Metf and VD3 prevented the increase in AChE activity when compared with the diabetic/saline group. In treated diabetic rats, the decrease in Na(+) K(+) -ATPase was reverted when compared with non-treated rats, but the increase in δ-ALA-D activity was not. VD3 prevented diabetes-induced TBARS level and improved memory. Our results show that VD3 can avoid cognitive deficit through prevention of changes in important enzymes such as Na(+) K(+) -ATPase and AChE in cerebral cortex in type 1 diabetic rats.
Assuntos
Colecalciferol/farmacologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Vitaminas/farmacologia , Acetilcolinesterase/metabolismo , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/psicologia , Ingestão de Alimentos/efeitos dos fármacos , Medo/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Masculino , Memória/efeitos dos fármacos , Metformina/farmacologia , Sintase do Porfobilinogênio/metabolismo , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Estreptozocina , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitaminas/uso terapêuticoRESUMO
Diabetes mellitus (DM) is associated with brain alterations that may contribute to cognitive dysfunctions. Chlorogenic acid (CGA) and caffeine (CA), abundant in coffee (CF), are natural compounds that have showed important actions in the brain. The present study aimed to evaluate the effect of CGA, CA, and CF on acetylcholinesterase (AChE), Na(+), K(+)-ATPase, aminolevulinate dehydratase (δ-ALA-D) activities and TBARS levels from cerebral cortex, as well as memory and anxiety in streptozotocin-induced diabetic rats. Animals were divided into eight groups (n = 5-10): control; control/CGA 5 mg/kg; control/CA 15 mg/kg; control/CF 0.5 g/kg; diabetic; diabetic/CGA 5 mg/kg; diabetic/CA 15 mg/kg; and diabetic/CF 0.5 g/kg. Our results demonstrated an increase in AChE activity and TBARS levels in cerebral cortex, while δ-ALA-D and Na(+), K(+)-ATPase activities were decreased in the diabetic rats when compared to control water group. Furthermore, a memory deficit and an increase in anxiety in diabetic rats were observed. The treatment with CGA and CA prevented the increase in AChE activity in diabetic rats when compared to the diabetic water group. CGA, CA, and CF intake partially prevented cerebral δ-ALA-D and Na(+), K(+)-ATPase activity decrease due to diabetes. Moreover, CGA prevented diabetes-induced TBARS production, improved memory, and decreased anxiety. In conclusion, among the compounds studied CGA proved to be a compound which acts better in the prevention of brain disorders promoted by DM.
Assuntos
Comportamento Animal/efeitos dos fármacos , Cafeína/farmacologia , Ácido Clorogênico/farmacologia , Café , Diabetes Mellitus Experimental/tratamento farmacológico , Acetilcolinesterase/biossíntese , Animais , Ansiedade/tratamento farmacológico , Peso Corporal/efeitos dos fármacos , Córtex Cerebral/metabolismo , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Sintase do Porfobilinogênio/biossíntese , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/biossíntese , Estreptozocina , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Cigarette smoke-exposure promotes neurobiological changes associated with neurocognitive abnormalities. Curcumin, a natural polyphenol, have shown to be able to prevent cigarette smoke-induced cognitive impairment. Here, we investigated possible mechanisms involved in curcumin protection against cigarette smoke-induced cognitive impairment and, due to its poor bioavailability, we investigated the potential of using curcumin-loaded lipid-core nanocapsules (C-LNC) suspension. Rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. Animals were divided into ten groups: I, control (vehicle/corn oil); II, curcumin 12.5mg/kg; III, curcumin 25mg/kg; IV, curcumin 50mg/kg; V, C-LNC 4 mg/kg; VI, tobacco exposed; VII, curcumin 12.5mg/kg along with tobacco exposure; VIII, curcumin 25mg/kg along with tobacco exposure; IX, curcumin 50mg/kg along with tobacco exposure; X, C-LNC 4 mg/kg along with tobacco exposure. Cigarette smoke-exposure impaired object recognition memory (P<0.001), indicated by the low recognition index, increased biomarkers of oxidative/nitrosative stress such as TBARS (P<0.05) and NOx (P<0.01), decreased antioxidant defenses such as NPSH content (P<0.01) and SOD activity (P<0.01) and inhibited the activities of enzymes involved in ion homeostasis such as Na(+),K(+)-ATPase and Ca(2+)-ATPase. Both curcumin formulations (free and nanoencapsulated) prevented the memory impairment, the redox imbalance and the alterations observed in the ATPases activities. Maintenance of ion homeostasis and redox balance is involved in the protective mechanism of curcumin against tobacco-induced cognitive impairment. Our results suggest that curcumin is a potential therapeutic agent for neurocognition and that C-LNC may be an alternative to its poor bioavailability.
Assuntos
Transtornos Cognitivos/prevenção & controle , Curcumina/farmacologia , Memória/efeitos dos fármacos , Nicotiana/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Fumaça/efeitos adversos , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Memória/fisiologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Oxirredução , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Cigarette smoke, a widely spread habit, is associated with a decline in cognitive function and studies have demonstrated that curcumin (Cur), an Indian spice, possesses a strong neuroprotective potential. Considering the relevance of investigating dietary compounds this study aimed to investigate the effect of Cur on memory and acetylcholinesterase (AChE) activity in brain structures and blood of cigarette smoke-exposed rats. Male Wistar rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. The experimental procedures were divided in two sets of experiments. In the first, the animals were divided into 4 groups: Vehicle (corn oil), Cur 12.5 mg/kg, Cur 25 mg/kg and Cur 50 mg/kg. In the second, the animals were divided into 5 groups: Vehicle (corn oil), Smoke, Smoke plus Cur 12.5 mg/kg, Smoke plus Cur 25 mg/kg and Smoke plus Cur 50 mg/kg. Treatment with Cur significantly prevented the decreased latency and cholinergic alterations in cigarette smoke-exposed rats. These AChE alterations could suggest a role in the memory impairment promoted by cigarette smoke-exposure and point toward the potential of Cur to modulate cholinergic neurotransmission and, consequently, improve cognition deficits induced by smoke. This study suggests that the dietary compound Cur may be involved in cholinergic system modulation and as a consequence exert an effect on learning and memory.
Assuntos
Acetilcolinesterase/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/tratamento farmacológico , Curcumina/uso terapêutico , Poluição por Fumaça de Tabaco/efeitos adversos , Análise de Variância , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Transtornos Cognitivos/enzimologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacosRESUMO
The aim of this study was to investigate the effect of the aqueous extract (AE) of Achyrocline satureioides on serum lipid profile, liver oxidative profile and Na(+),K(+)-ATPase activity of rats submitted to a hyperlipidic diet. The animals were divided into four groups: control (C), AE 10% (A(10)), hyperlipidic (H) and hyperlipidic/AE 10% (HA(10)). In serum, we measured the levels of total cholesterol (TC), high-density lipoprotein, very-low-density lipoprotein, low-density lipoprotein (LDL) and triglyceride (TG). In liver homogenates, we measured the thiobarbituric acid reactive substances, the carbonyl proteins, the non-protein thiols (NPSHs) and the activity of superoxide dismutase, catalase (CAT) and Na(+),K(+)-ATPase. We observed a significant increase in the TC and LDL levels in the H group. A. satureioides prevented these effects, decreased the TG levels in the HA(10) group and increased the NPSH levels in the A(10) and HA(10) groups. The H group showed an increase in the carbonyl protein level and a decrease in CAT and Na(+),K(+)-ATPase activities. With the use of this model, results show that increased levels of lipids are related to a redox imbalance in the liver, which is also related to the inhibition of Na(+),K(+)-ATPase activity, and that chronic administration of the AE of A. satureioides is capable of changing this profile.