Eduardo Benedetti Parisotto

Creatine monohydrate supplementation is commonly combined with exercise training to promote muscle hypertrophy and enhance performance. This study investigated the effects of creatine monohydrate supplementation on hepatic markers of tissue damage, lipoperoxidation intensity, and enzymatic antioxidant cofactor levels in healthy rats submitted to high-intensity interval training (HIIT). Male Wistar rats were assigned to four groups: sedentary control (C), sedentary creatine supplementation (Cr), HIIT (HT), and HIIT combined with creatine supplementation (HTC). The C and HT groups received standard commercial chow, whereas the Cr and HTC groups received a diet supplemented with 2% creatine. The HT and HTC groups also completed a 12-week treadmill HIIT protocol. After the intervention, biochemical profile, serum liver function markers, and hepatic morphology were analyzed. Malondialdehyde (MDA) levels were assessed as a marker of lipoperoxidation, while hepatic Cu, Mn, Zn, and Se levels were measured as antioxidant cofactors using spectrophotometry. Results were analyzed using two-way ANOVA followed by appropriate post hoc tests. HIIT was associated with greater running distance and maximal speed than the sedentary condition. Creatine supplementation increased alkaline phosphatase levels, whereas HIIT increased serum creatinine and reduced serum triacylglycerol levels. In the liver, HIIT increased MDA and decreased selenium levels independently of creatine supplementation. These changes were not accompanied by histopathological evidence of hepatic damage. In conclusion, HIIT induced lipoperoxidation that was not counterbalanced by enzymatic antioxidant processes related to Cu, Mn, Zn, and Se cofactors, resulting in relative hepatic antioxidant imbalance without tissue damage. Creatine supplementation did not modify the effects of exercise training on the liver.

Oxidative stress (OS) plays a key role in the pathophysiology of COVID-19 and may be associated with sequelae after severe SARS-CoV-2 infection. This study evaluated OS and inflammation biomarkers in blood from individuals with post-acute sequelae of COVID-19 (PASC). 64 male and female participants were distributed into three groups: healthy individuals (n = 20), acute COVID-19 patients (symptoms for 12 weeks, n = 29). Analyses included inflammatory cytokines, myeloperoxidase (MPO) activity, and OS markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), gamma-glutamyl transferase (GGT), reduced glutathione (GSH), uric acid (UA), thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC). Individuals with PASC showed increased IL-6 and IL-8. Both COVID-19 groups exhibited decreased SOD and CAT. GST decreased only in the acute group. Elevated GGT and GSH were found in the PASC group. High UA levels were observed in PASC individuals. There were no changes in TBARS values ⁣⁣in the PASC group. However, PC concentrations were elevated only in this group. Correlations were identified between inflammatory markers and OS parameters. These findings suggest that individuals with PASC pronounced OS, which potentially exacerbates disease complications. Monitoring OS biomarkers could aid in patient prognosis and management.

The aim of this study was to evaluate the effect of ylang-ylang (Cananga odorata) essential oil (YEO) on models of experimental arthritis, persistent inflammation, and nociception in mice. YEO treatment at doses of 100 and 200 mg/kg reduced the infiltration of leukocytes into the joint cavities of mice submitted to zymosan-induced arthritis 6 h and 7 days after arthritis induction. At these doses, YEO treatment reduced the formation of joint edema 4 and 6 h after arthritis induction, and at a dose of 200 mg/kg, YEO treatment reduced mechanical hyperalgesia 3 and 4 h after arthritis induction. At the dose of 200 mg/kg, YEO treatment reduced interleukin-6 (IL-6) levels and cartilage destruction in the zymosan-induced arthritis model, and reduced edema formation and mechanical hyperalgesia in the model of persistent inflammation (21 days) induced by complete Freund’s adjuvant (CFA) in mice. YEO treatment at a dose of 200 mg/kg reduced the nociceptive response in experimental models of nociception induced by acetic acid and formalin. The YEO treatment reduced inflammatory parameters in the experimental arthritis model, and presented antiarthritic, anti-hyperalgesic, antinociceptive, and anti-inflammatory properties.

The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 μg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. These compounds included selenium-substituted indole, coumarin, chromone, oxadiazole, imidazo[1,2-a]pyridine, Imidazo[2,1-b]thiazole, and oxazole, among others. These compounds were screened against Leishmania amazonensis promastigotes and intracellular amastigotes, and their cytotoxicity was assessed in peritoneal macrophages, NIH/3T3, and J774A.1 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes with reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC₅₀ values of 3.97 µM and 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in host cells (CC₅₀ > 200 µM). Also, compounds MRK-107 and MRK-113 showed activity against intracellular amastigotes (IC50 18.31 and 15.93 µM and SI 12.55 and 10.92, respectively). In conclusion, the identified selenium-containing compounds hold potential structures as antileishmanial drug candidates to be further explored in subsequent studies. These findings represent a significant step toward the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. The compounds were subjected to screening against L. amazonensis promastigotes, and their cytotoxicity was assessed in NIH/3T3 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes while demonstrating reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM, 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in NIH/3T3 cells (CC50 > 200 µM). Although these results are promising, additional investigations focusing on intracellular amastigotes are required to determine the antileishmanial activity of the compounds. In conclusion, the identified selenium-containing compounds hold considerable potential as antileishmanial drug candidates and warrant further exploration in subsequent studies. These findings represent a significant step towards the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

Colon cancer incidence rates are increasing annually, a scenario aggravated by genetic and epigenetic alterations that promote drug resistance. Recent studies showed that novel synthetic selenium compounds are more efficient and less toxic than conventional drugs, demonstrating biocompatibility and pro-oxidant effects on tumor cells. This study aimed to investigate the cytotoxic effect of MRK-107, an imidazo [1,2- a]pyridine derivative, in 2D and 3D cell culture models of colon cancer (Caco-2 and HT-29). Sulforhodamine B results revealed a GI50 of 2.4 µM for Caco-2, 1.1 µM for HT-29, and 22.19 µM for NIH/3T3 in 2D cultures after 48 h of treatment. Cell recovery, migration, clonogenic, and Ki-67 results corroborated that MRK-107 inhibits cell proliferation and prevents cell regeneration and metastatic transition by selectively reducing migratory and clonogenic capacity; non-tumor cells (NIH/3T3) re-established proliferation in less than 18 h. The oxidative stress markers DCFH-DA and TBARS revealed increased ROS generation and oxidative damage. Caspases-3/7 are activated and induce apoptosis as the main mode of cell death in both cell models, as assessed by annexin V-FITC and acridine orange/ethidium bromide staining. MRK-107 is a selective, redox-active compound with pro-oxidant and pro-apoptotic properties and the capacity to activate antiproliferative pathways, showing promise in anticancer drug research.