Antinociceptive effect of Nephelium lappaceum L. fruit peel and the participation of nitric oxide, opioid receptors, and ATP-sensitive potassium channels

Introduction:Nephelium lappaceum L. (Sapindaceae) is a plant known as rambutan. It is used for various purposes in traditional medicine.Objective: We aimed to evaluate the antinociceptive effects of the ethanol extract of the fruit peel of N. lappaceum (EENL), the mechanisms involved in these effects, and the acute toxicity in zebrafish.Methods: We performed chromatography coupled to mass spectrometry, acute toxicity assay in zebrafish, and evaluation in mice submitted to models of nociception and locomotor activity.Results: We identified (epi)-catechin, procyanidin B, and ellagic acid and its derivatives in EENL. We did not find any toxicity in zebrafish embryos incubated with EENL. The locomotor activity of mice submitted to oral pretreatment with EENL was not changed, but it reduced the abdominal constrictions induced by acetic acid, the licking/biting time in both the first and second phase of formalin testing and capsaicin testing, and carrageenan-induced paw mechanical allodynia. Oral pretreatment with EENL increased latency time in the hot plate test. This antinociceptive effect was significantly reversed by naloxone, L-arginine, and glibenclamide respectively showing the participation of opioid receptors, nitric oxide, and KATP channels as mediators of EENL-induced antinociception.Conclusion: EENL causes antinociception with the participation of opioid receptors, nitric oxide, and KATP channels, and is not toxic to zebrafish

Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats

PURPOSE: To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion. METHODS: Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed. RESULTS: OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1&#946;, TNF-&#945; and IL-10 remained below the detection limit in all groups. CONCLUSIONS: In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion. METHODS: Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed. RESULTS: OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1&#946;, TNF-&#945; and IL-10 remained below the detection limit in all groups. CONCLUSIONS: In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations28424525

Evaluation of Muscle Damage, Body Temperature, Peak Torque and Fatigue Index in Three Different Methods of Strength Gain

International Journal of Exercise Science 13(3): 1352-1365, 2020. The aim of this study was to evaluate and compare three different strength training protocols for the lower limbs by using biochemical indicators of muscle damage, thermographic analysis, and neuromuscular performance. In total, 10 men (age: 22.50 ± 2.84 years; weight, 75.45 ± 6.86 kg) completed the study. All the athletes were subjected to three methods of resistance training (RT): traditional, tension, and occlusion training. Serum concentrations of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were used as indicators of muscle damage. To measure muscle strength, the peak force, and fatigue index were determined using a Kratos load cell. Images were captured using an infrared camera (FLIR T640sc). The vascular occlusion method demonstrated a 33% reduction in post-training peak torque (p \u3c 0.001; ɳ2p: 2.74), which was recovered within 24 h (p \u3c 0.001; ɳ2p: 1.08). The thermographic analysis revealed a reduction in skin temperature in both thighs after the tension (−9.37%) and vascular occlusion (−6.01%) methods. In conclusion, the occlusion training seems to provide additional benefits as compared to the other two methods of strength training

Effects of Resistance Training on Oxidative Stress Markers and Muscle Damage in Spinal Cord Injured Rats

Background: Spinal cord injury (SCI) is a condition that affects the central nervous system, is characterized by motor and sensory impairments, and impacts individuals’ lives. The objective of this study was to evaluate the effects of resistance training on oxidative stress and muscle damage in spinal cord injured rats. Methodology: Forty Wistar rats were selected and divided equally into five groups: Healthy Control (CON), Sham (SHAM) SCI Untrained group (SCI-U), SCI Trained group (SCI- T), SCI Active Trained group (SCI- AT). Animals in the trained groups were submitted to an incomplete SCI at T9. Thereafter, they performed a protocol of resistance training for four weeks. Results: Significant differences in muscle damage markers and oxidative stress in the trained groups, mainly in SCI- AT, were found. On the other hand, SCI- U group presented higher levels of oxidative stress and biomarkers of LDH and AST. Conclusion: The results highlight that resistance training promoted a decrease in oxidative stress and a significative response in muscle damage markers. Keywords: spinal cord injury; resistance training; oxidative stress; muscle damag

Characterization of the acute pancreatitis induced by secretory phospholipases A2

Orientador: Edson AntunesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A pancreatite aguda e uma doença inflamatória do pâncreas caracterizada por intensa necrose pancreática e efeitos sistêmicos secundários como lesão pulmonar, os quais são a principal causa da mortalidade observada nessa doença. Ha evidencia de que as fosfolipases A2 (PLA2) tem um importante papel na fisiopatologia da pancreatite aguda. O objetivo deste trabalho foi investigar a capacidade de PLA2s de induzir pancreatite em ratos e os mecanismos envolvidos nesse fenômeno. As seguintes PLA2s foram utilizadas: piratoxina-I (homologo Lys-49 de PLA2 desprovido de atividade catalitica), bothropstoxina-II (homologo Asp-49 de PLA2 com baixa atividade catalítica) e a PLA2 proveniente do veneno de Naja moçambique moçambique (que possui alta atividade catalítica). Ratos Wistar machos (200-250 g) provenientes do CEMIB/UNICAMP foram utilizados. As PLA2s foram injetadas no ducto biliopancreatico de animais anestesiados e apos diferentes tempos experimentais foram avaliados o extravasamento de proteínas plasmáticas no pâncreas, infiltrado de neutrofilos no pâncreas e pulmão e amilase serica. A analise histológica do pâncreas e pulmão também foi realizada em alguns grupos experimentais. Piratoxina-I foi capaz de causar extravasamento de proteínas plasmáticas no pâncreas, infiltrado de neutrofilos no pulmão e os níveis sericos de amilase. Alem disso, a piratoxina-I causou alterações histológicas nos tecidos pancreático (infiltrado de neutrofilos, necrose de células acinares e edema intersticial) e pulmonar (edema intersticial e diminuição do espaço alveolar), que foram mais evidentes nos tempos iniciais da pancreatite (4-12h). Bothropstoxina-II e a PLA2 do veneno de Naja moçambique moçambique, a semelhança da Piratoxina-I, também foram capazes de aumentar o extravasamento de proteínas plasmáticas e o influxo de neutrofilos no tecido pancreático por mecanismos nao relacionados a sua atividade catalítica. Entretanto, o influxo de neutrofilos para o pulmão e o aumento dos níveis sericos de amilase causados por essas PLA2s foi dependente de sua atividade catalítica. As PLA2s também causaram secreção deamilase de acinos pancreáticos isolados, que foi dependente da atividade catalítica dessas enzimas. Adicionalmente, com o objetivo de entender o mecanismo envolvido na pancreatite induzida pela PLA2 de Naja mocambique mocambique animais foram tratados com os seguintes agentes farmacológicos: pentoxifilina (inibidor da sintese de TNF-á), SR140333 (antagonista de receptor NK1), icatibant (antagonista de receptor B2), L-NAME (inibidor não seletivo das NOS), aminoguanidina (inibidor preferencial da NOS induzivel), indometacina (inibidor não seletivo de COX), celecoxib (inibidor seletivo de COX-2), PCA4248 (antagonista dos receptores de PAF) e AA861 (inibidor da 5-lipoxigenase). Em conjunto, nossos dados mostraram que os efeitos locais e secundários são multimediados, envolvendo a participação de bradicinina, substancia P, NO, TNF-á, PAF e metabolitos das COXs. Em conclusão, demonstramos que as PLA2s secretorias são capazes de induzir pancreatite aguda em ratos quando injetadas no ducto biliopancreatico, um quadro caracterizado por efeitos inflamatórios locais e secundários cuja mediação farmacológica envolve vários fatores. Alem disso, a pancreatite aguda induzida pelas PLA2s reproduz algumas alterações observadas na pancreatite aguda em humanos, representando uma nova estratégia de estudo da fisiopatologia da pancreatite agudaAbstract: Acute pancreatitis is an inflammatory disease of the pancreas that is characterized by intense pancreatic necrosis and remote systemic effects such as the lung injury that is the main cause of death during acute pancreatitis. There are evidences that phospholipases A2 (PLA2) have an important role in the acute pancreatitis pathophysiology. The aim of this work was to investigate the ability of PLA2 to induce acute pancreatitis in rats, and the mechanisms underlying this phenomenon. The following PLA2s were used: piratoxin-I (a Lys-49 PLA2 homologue devoid of catalytic activity), bothropstoxin-II (an Asp-49 PLA2 homologue with low catalytic activity) and PLA2 from Naja mocambique mocambique venom (high catalytic activity). Male Wistar rats (200-250g) provided by CEMIBUNICAMP have been used. The PLA2s were injected into the common bile duct of anesthetized rats, after which pancreatic plasma protein extravasation, pancreatic and lung neutrophil infiltration and serum levels of amylase were measured. Histology of the pancreatic and lung tissue has also been carried out in some experimental group. Piratoxin-I was able to increase the pancreatic plasma protein extravasation, lung neutrophil infiltration and serum amylase levels. In addition, Piratoxin-I caused histological changes in the pancreatic (neutrophil infiltration, areas of acinar cell necrosis and interstitial edema) and lung (interstitial edema and diminuition of alveolar space) tissues, which were more evident in the early periods (4-12h) after the injection. Bothropstoxin-II and PLA2 from Naja mocambique mocambique venom were also able to increase the plasma protein extravasation and neutrophil influx in the pancreatic tissue by mechanisms unrelated to their catalytic activity. However, the remote lung neutrophil influx caused by these PLA2s was shown to depend on their catalytic activity. The enhancement of serum amylase levels was also dependent on the catalytic activity of these enzymes. The PLA2s also caused amylase secretion from isolated pancreatic acini, which was dependent on their catalytic activity. Next, in order to further understand the mechanisms involved in pancreatitis induced by PLA2 Naja mocambique mocambique, animals were treated with the following pharmacological agents: pentoxifylline (TNF-á synthesis inhibitior), SR140333 (NK1receptor antagonist), icatibant (B2 receptor antagonist), L-NAME (non-selective NOS inhibitor), aminoguanidine (preferential inducible NOS inhibitor), indomethacin (nonselective COX inhibitor), celecoxib (selective COX-2 inhibitor), PCA4248 (PAF receptor antagonist) and AA861 (5-lipoxygenase inhibitor). Taken together our data showed that local and remote effects are multimediated, involving the participation of bradykinin, substance P, NO, TNF-á, PAF and COXs metabolites. In conclusion, we have shown that secretory PLA2s are able to induce acute pancreatitis in rats when injected into the common bile duct. Therefore, PLA2-induce acute pancreatitis reproduces some aspects of the human disorder representing a new strategy to study the pathophysiology of acute pancreatitisDoutoradoFarmacologiaDoutor em Farmacologi

Vaccinium macrocarpon

We evaluated the effect of the hydroethanolic extract of fruits of Vaccinium macrocarpon (HEVm) in a model of acute pancreatitis (AP) in mice. AP was induced by two injections of L-arginine and animals were treated with HEVm (50, 100, and 200 mg/kg, p.o.) or vehicle (saline) every 24 h, starting 1 h after the induction of AP. Phytochemical analysis of the extract and measurement of inflammatory and oxidative stress parameters, as well as abdominal hyperalgesia, were performed. Catechin, epicatechin, rutin, and anthocyanins were identified in HEVm. Treatment with HEVm decreased L-arginine-induced abdominal hyperalgesia (from 48 to 72 h). Also, treatment with HEVm decreased L-arginine-induced pancreatic edema, pancreatic and pulmonary neutrophil infiltration, and levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6, after 72 h of induction. L-arginine-induced hyperamylasemia and hyperlipasemia were also reduced by the treatment with HEVm in comparison to vehicle-treated group. Moreover, lipoperoxidation, carbonyl radicals, nonprotein sulfhydryl groups, and activity of catalase and superoxide dismutase, but not glutathione peroxidase, were restored by the treatment with HEVm. These results show that treatment with HEVm decreased hyperalgesia and pancreatic/extrapancreatic inflammation and oxidative damage in L-arginine-induced AP, making this extract attractive for future approaches designed to treat this condition