Guilherme de Paula Costa

Dietary supplements have improved performance and muscle hypertrophy in athletes and nonathletes in the past few decades. Theracurmin, a nutraceutical supplement based on curcumin, has been highlighted by its anti-inflammatory and antioxidant properties in physiological and pathological conditions. This study aimed to investigate the effects of theracurmin intake (300 mg/kg), containing 30 mg/kg of curcumin, in male Swiss mice (n = 66) under distinct protocols of climbing stairs (strength exercise) and their respective detraining period. Animals, aged 7–9 weeks, were trained for 8 weeks (5 days/week), with a minimum interval of 24 hr between each session, followed by a 4-week detraining period. After euthanasia, skeletal muscle hypertrophy was evaluated through histological analysis. Tissue inflammatory release of tumor necrosis factor, interleukin (IL)-6, IL-10, and chemokine C–C motif ligand 2, as well as the activity of oxidative stress enzymes (catalase, superoxide dismutase, and lipid peroxidation), were also assessed. In trained animals, inflammatory mediators and skeletal muscle mass increased after training (p = .0004). Theracurmin did not revert the muscle hypertrophy, but it decreased tissue chemokine C–C motif ligand 2 (p = .0001) and lipid peroxidation (p < .0001) after strength training and after detraining (p = .0008 and p = .001, respectively). Tissue tumor necrosis factor was only reduced during the detraining period (p = .037), whereas IL-6 (p = .0001) and IL-10 (p < .0001) increased after the training protocol. No differences were observed in catalase and superoxide dismutase. Our data suggest that theracurmin intake contributes to the reduction of tissue inflammatory mediators during strength training and/or detraining without essential activity on skeletal muscle hypertrophy.

Leishmania amazonensis can cause cutaneous and visceral clinical manifestations of leishmaniasis in infected hosts. Once the treatment against disease is toxic, presents high cost, and/or there is the emergence of parasite-resistant strains, alternative means through which to control the disease must be developed. In this context, immunotherapeutics combining known drugs with immunogens could be applied to control infections and allow hosts to recover from the disease. In this study, immunotherapeutics protocols associating mimotopes selected by phage display and amphotericin B (AmpB) were evaluated in L. amazonensis-infected mice. Immunogens, A4 and A8 phages, were administered alone or associated with AmpB. Other animals received saline, AmpB, a wild-type phage (WTP), or WTP/AmpB as controls. Evaluations performed one and thirty days after the application of immunotherapeutics showed that the A4/AmpB and A8/AmpB combinations induced the most polarized Th1-type immune responses, which reflected in significant reductions in the lesion’s average diameter and in the parasite load in the infected tissue and distinct organs of the animals. In addition, the combination also reduced the drug toxicity, as compared to values found using it alone. In this context, preliminary data presented here suggest the potential to associate A4 and A8 phages with AmpB to be applied in future studies for treatment against leishmaniasis.

Cigarette smoking throughout life causes serious health issues in the lungs. The electronic cigarette (E‐Cig) use increased, since it was first introduced in the world. This research work compared the short‐term exposure consequences to e‐cigarette vapor and cigarette smoke in male mice. Forty‐five C57BL/6 mice were randomized into control (C) in an ambient air exposition cigarette smoke (CS) and aerosol electronic cigarette (EC), both were exposed to 120 puffs, 3 times/day during five days. Then, in the experimental protocol, the euthanized mice had their tissues removed for analysis. Our study showed that CS and EC resulted in higher cell influx into the airways, and an increase in macrophage counts in CS (209.25 ± 7.41) and EC (220.32 ± 8.15) when compared to C (108.40 ± 4.49) (p < 0.0001). The CS (1.92 ± 0.23) displayed a higher pulmonary lipid peroxidation as opposed to C (0.93 ± 0.06) and EC (1.23 ± 0.17) (p < 0.05). The EC (282.30 ± 25.68) and CS (368.50 ± 38.05) promoted increased levels of interleukin 17 when compared to C (177.20 ± 10.49) (p < 0.05). The EC developed shifts in lung histoarchitecture, characterized by a higher volume density in the alveolar air space (60.21; 55.00‐65.83) related to C (51.25; 18.75‐68.75) and CS (50.26; 43.75‐62.08) (p =0.002). The EC (185.6 ± 9.01) presented a higher respiratory rate related to CS (133.6 ± 10.2) (p < 0.002). Therefore, our findings demonstrated that the short‐term exposure to e‐cig promoted more acute inflammation comparing to cigarette smoke in the ventilatory parameters of the animals.

Background: to evaluate the effects of one week of supplementation with curcumin combined with piperine on physical performance, immune system cell counts, muscle damage, and plasma levels of inflammatory markers after a treadmill running training session. Methods: This study is a double-blind, crossover-balanced clinical trial with a three-week intervention. Sixteen male runners with a mean age of 36 ± 9 years and VO2 max of 60.6 ± 9.03 mL.kg ⁻¹ min ⁻¹ were recruited and randomly divided into 2 groups: the first group (CPG) was supplemented daily for 7 days with 500 mg of curcumin + 20 mg piperine, and the second group (PG) was supplemented with 540 mg of cellulose. After the 7th day of supplementation, the volunteers participated in the experimental running protocol, where blood samples were collected before, after, and one hour after exercise for analysis of the number of leukocytes, creatine kinase, and cytokine concentration (IL-2, TNF-α, IFN, IL-6, and IL-10) using flow cytometry. This process was repeated, reversing the supplementation offered to the groups. Results: curcumin and piperine supplementation could not change the physical performance, immune cell counts, and muscle damage; however, the aerobic fatiguing exercise protocol inhibited the elevation of the plasmatic levels of some cytokines. The running exercise protocol could elevate the circulating levels of IL-2 (from 49.7 to 59.3 pg/mL), TNF-α (from 48.5 to 51.5 pg/mL), INF (from 128.8 to 165.0 pg/mL), IL-6 (from 63.1 to 77.3 pg/mL), and IL-10 (from 48.9 to 59.6 pg/mL) 1 h after the end of the running protocol. However, the curcumin and piperine supplementation could inhibit this elevation. Conclusions: curcumin and piperine supplementation had no effect on physical performance, immune cell counts, or muscle damage; however, the supplementation could modulate the kinetics of IL-2, TNF-α, INF, IL-6, and IL-10 1 h after the end of exercise.

Cigarette smoke (CS) is the major cause of preventable death worldwide, and it can also cause damage to extrapulmonary organs, such as the liver, mainly due the generation of reactive oxygen species (ROS). The liver is an essential organ for human survival since it is mainly responsible for the body metabolism and among other things and it is the place where many endogenous and exogenous substances undergo biological transformation. Lycopene is a nonprovitamin A carotenoid found in red fruits and vegetables, and its role as a potent antioxidant is well known. In this study, we hypothesized that lycopene could protect mouse liver against long‐term CS exposure. Thirty C57BL/6 mice were exposed to twelve cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 25 mg/kg/day or 50 mg/kg/day of lycopene via orogastric gavage. After euthanasia, the hepatic tissue was collected for histopathological, antioxidant defense, oxidative stress, inflammatory, and collagen deposition analysis. Our analysis demonstrated that lycopene results in a suitable outcome to ameliorate the pathological changes, inflammatory and antioxidant profile in a mouse model of long‐term CS exposure, and collagen accumulation in the hepatic extracellular matrix. This study demonstrates for the first time that supplementation of lycopene can be a possible pharmacological tool for the treatment of hepatic damage caused by exposure to long‐term CS.

Habitual food intake and physical activity can affect chronic low‐grade inflammation, which is common in the elderly, because of changes in the immune system and body composition. Thus, the present study proposes an evaluation of the influence of past eating habits on the effects of an intervention of resistance training plus dietary advice on the inflammatory profile of the elderly. We conducted an intervention study with 40 elderly people. The Revised Diet Quality Index (HEI‐R) and the dietary total antioxidant capacity (dTAC) were calculated before the intervention based on a food frequency questionnaire validated to the elderly population. Participants were categorized according to the median of HEI‐R and dTAC to assess the influence of the habitual diet quality on anthropometry and inflammatory markers (CRP, IL‐8, CCL‐2, and leptin) before and after the intervention. The 19‐week intervention provided a long‐term progressive resistance training associated with dietary advice focused on foods rich in compounds with anti‐inflammatory and antioxidant properties. There was a greater reduction in weight, body mass index (BMI), and body fat (%) in the group with the lowest HEI‐R and a greater reduction in the body fat (%) in the group with the lowest dTAC, indicating that the group that had a worse diet quality before the intervention responded better to it. The index HEI‐R correlated negatively with Δweight and ΔBMI. dTAC correlated positively with Δmonocyte 1 chemotactic protein (CCL‐2) and ΔC‐reactive protein (CRP). In this scenario, elderly persons with bad habits can benefit from interventions to lifestyle change, while the better diet quality including dietary antioxidant sources can be useful to control weight and inflammatory biomarkers in this population.

Mechanical ventilation (MV) is essential for the treatment of critical patients since it may provide a desired gas exchange. However, MV itself can trigger ventilator‐associated lung injury in patients. We hypothesized that the mechanisms of lung injury through redox imbalance might also be associated with pulmonary inflammatory status, which has not been so far described. We tested it by delivering different tidal volumes to normal lungs undergoing MV. Healthy Wistar rats were divided into spontaneously breathing animals (control group, CG), and rats were submitted to MV (controlled ventilation mode) with tidal volumes of 4 mL/kg (MVG4), 8 mL/kg (MVG8), or 12 mL/kg (MVG12), zero end‐expiratory pressure (ZEEP), and normoxia (FiO₂ = 21%) for 1 hour. After ventilation and euthanasia, arterial blood, bronchoalveolar lavage fluid (BALF), and lungs were collected for subsequent analysis. MVG12 presented lower PaCO₂ and bicarbonate content in the arterial blood than CG, MVG4, and MVG8. Neutrophil influx in BALF and MPO activity in lung tissue homogenate were significantly higher in MVG12 than in CG. The levels of CCL5, TNF‐α, IL‐1, and IL‐6 in lung tissue homogenate were higher in MVG12 than in CG and MVG4. In the lung parenchyma, the lipid peroxidation was more important in MVG12 than in CG, MVG4, and MVG8, while there was more protein oxidation in MVG12 than in CG and MVG4. The stereological analysis confirmed the histological pulmonary changes in MVG12. The association of controlled mode ventilation and high tidal volume, without PEEP and normoxia, impaired pulmonary histoarchitecture and triggered redox imbalance and lung inflammation in healthy adult rats.

Cigarette smoke is highly toxic, and it can promote increased production of reactive species and inflammatory response and leads to liver diseases. Quercetin is a flavonoid that displays antioxidant and anti‐inflammatory activities in liver diseases. This study aimed at evaluating the protective effects of quercetin on livers from mice exposed to long‐term cigarette smoke exposure. Male C57BL/6 mice were divided into five groups: control (CG), vehicle (VG), quercetin (QG), cigarette smoke (CSG), quercetin, and cigarette smoke (QCSG). CSG and QCSG were exposed to cigarette smoke for sixty consecutive days; at the end of the exposures, all animals were euthanized. Mice that received quercetin daily and were exposed to cigarette smoke showed a reduced influx of inflammatory cells, oxidative stress, inflammatory reaction, and histopathological changes in the liver, compared to CSG. These results suggest that quercetin may be an effective adjuvant for treating damage to the liver due to cigarette smoke exposure.

In addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia. Male BALB/c mice (8–10 weeks), a strain highly sensitive to hyperoxia, received the exogenous surfactant-containing protein SP-B and SP-C by intranasal instillation 12 h before starting 24 h of exposure to hyperoxia in an inhalation chamber and were compared to mice receiving hyperoxia alone and to controls subjected to normoxia. Compared to the hyperoxia group, the administration of exogenous surfactant was able to reduce lung inflammation through a reduction in the influx of neutrophils and inflammatory biomarkers such as TNF, IL-17, and HMGB1 expression. The antioxidant activity prevented oxidative damage by reducing lipid peroxidation and protein carbonylation and increasing superoxide dismutase activity when compared to the hyperoxia group. Our results offer new perspectives on the effects and the mechanism of exogenous surfactant in protecting the airway and lungs, in oxygen-rich lung microenvironment, against oxidative damage and aggravation of acute inflammation induced by hyperoxia.