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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.

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Snake bites are a severe problem in the countryside of Brazil and are usually attributed to snakes of the genera Bothrops, Crotalus, and Lachesis. Snake venom can release ectoenzymes and nucleotidases that modulate the purinergic system. In addition to serum therapy against snake poisoning, medicinal plants with anti-inflammatory activities, such as Tabebuia aurea, is empirically applied in accidents that occur in difficult-to-access areas. This study aimed was to verify the presence and activity of nucleotidases in the crude venom of Bothrops mattogrossensis (BmtV) in vitro and characterize the modulation of purinergic components, myeloid differentiation, and inflammatory/oxidative stress markers by BmtV in vivo and in vitro. Moreover, our study assessed the inhibitory activities of specioside, an iridoid isolated from Tabebuia aurea, against the effects of BmtV. Proteomic analysis of venom content and nucleotidase activity confirm the presence of ectonucleotidase-like enzymes in BmtV. In in vivo experiments, BmtV altered purinergic component expression (P2X7 receptor, CD39 and CD73), increased neutrophil numbers in peripheral blood, and elevated oxidative stress/inflammatory parameters such as lipid peroxidation and myeloperoxidase activity. BmtV also decreased viability and increased spreading index and phagocytic activity on macrophages. Specioside inhibited nucleotidase activity, restored neutrophil numbers, and mediate the oxidative/inflammatory effects produced by BmtV. We highlight the effects produced by BmtV in purinergic system components, myeloid differentiation, and inflammatory/oxidative stress parameters, while specioside reduced the main BmtV-dependent effects.

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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.

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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.

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Coronavirus disease (COVID-19) is an acute respiratory disease caused by the new coronavirus (SARS-CoV-2) that has spread throughout the world causing millions of deaths. COVID-19 promotes excessive release of pro-inflammatory cytokines leading to acute lung injury and death. Reactive oxygen species (ROS) and oxidative stress (OS) may also play a role in the pathophysiology of COVID-19. The present study investigated levels of inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12) and OS biomarkers (MPO, SOD, CAT, GST enzymes and contents of GSH, TBARS and PC) in patients with SARS-CoV-2 infection, which were correlated with disease severity. Patients with SARS significantly increased IL-1ß levels, while IL-6 levels were elevated in both groups of SARS-CoV-2 positive patients. The most severe patients showed increased levels of IL-8 and IL-10, while subjects without SARS showed lower values. MPO activity were higher in both groups of SARS-CoV-2 positive patients, while SOD and CAT activity were decreased in both groups. Compared to controls, GGT was elevated only in the SARS patient group, while GST values were increased in the group of positive patients in SARS-CoV-2 without SARS and were decreased in patients with SARS. GSH and UA contents decreased in SARS-CoV-2 positive subjects, whereas TBARS and PC contents increased in both groups of SARS-CoV-2 positive patients, particularly in the SARS patient group. In addition, several important correlations were found between cytokines and the different OS parameters suggesting some inter-relationship in the complex antioxidant system of the patients. In general, patients with SARS-CoV-2 infection showed higher levels of OS biomarkers, and also elevated contents of IL-6 and IL-10, probably worsening the damage caused by SARS-CoV-2 infection. This damage may contribute to the severity of the disease and its complications, as well as a prognosis for SARS-CoV-2 patients.

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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.

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ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Miconia albicans have been extensively used as a traditional medicine to treat inflammation, infection, arthritis, joint pain, and analgesia, which can be purchased easily. Nevertheless, the scientific evidence of chemical profile identification and toxicity investigation is meager. AIM OF THE STUDY: This study aimed to determine the chemical profile of Miconia albicans aqueous extract (MAAE), to investigate its anti-inflammatory and hyperalgesic effects, and toxicity (acute and repeated-dose oral) in vivo studies. MATERIALS AND METHODS: MAAE was obtained by infusion method and its chemical constituents were analyzed and annotated by LC-DAD-MS. The in vivo tests were performed with male and female Swiss mice. Toxicity studies were examined by acute (2000 mg/kg) and repeated-dose oral assays (51.2; 256; 1280 mg/kg); anti-inflammatory evaluation was performed by paw edema and leukocyte migration, and anti-hyperalgesic properties were analyzed by abdominal writhing induced by acetic acid and formalin. The animals were treated by oral means with 51.2, 256, and 1280 mg/kg of MAAE. RESULTS: Twenty-four compounds were annotated from MAAE by LC-DAD-MS, such as ellagitannins, ellagic acid derivatives, flavan-3-ol, and O-glycosylated compounds, including flavonols, triterpenes, and megastigmanes. MAAE induced no significant toxicological effects in the acute and repeated-dose oral assays at lower doses and no histological changes were observed. Hematological and biochemical showed no significant alterations. The oral administration of MAAE 256 mg/kg inhibited the edematogenic effect and reduced the leukocyte migration. In addition, MAAE decreased the abdominal writhings induced by acetic acid and the paw-licking time by formalin assay. CONCLUSION: MAAE showed a significant reduction in inflammatory levels and leukocyte migration, revealing anti-hyperalgesic properties. Additionally, MAAE revealed no acute and repeated-doses toxicities.

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Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.

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The present study investigated the effects of perinatal exposure to glyphosate-based herbicide (GBH) in offspring's liver. Pregnant Wistar rats were exposed to GBH (70 mg glyphosate/Kg body weight/day) in drinking water from gestation day 5 to postnatal day 15. The perinatal exposure to GBH increased 45Ca2+ influx in offspring's liver. Pharmacological tools indicated a role played by oxidative stress, phospholipase C (PLC) and Akt pathways, as well as voltage-dependent Ca2+ channel modulation on GBH-induced Ca2+ influx in offspring's liver. In addition, changes in the enzymatic antioxidant defense system, decreased GSH content, lipid peroxidation and protein carbonylation suggest a connection between GBH-induced hepatotoxic mechanism and redox imbalance. The perinatal exposure to GBH also increased the enzymatic activities of transaminases and gamma-glutamyl transferase in offspring's liver and blood, suggesting a pesticide-induced liver injury. Moreover, we detected increased iron levels in liver, blood and bone marrow of GBH-exposed rats, which were accompanied by increased transferrin saturation and decreased transferrin levels in blood. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were increased in the liver of rats perinatally exposed to GBH, which were associated with. Increased phospho-p65NFκB immunocontent. Therefore, we propose that excessive amounts of iron in offspring's liver, blood and bone marrow induced by perinatal exposure to GBH may account for iron-driven hepatotoxicity, which was associated with Ca2+ influx, oxidative damage and inflammation. Further studies will clarify whether these events can ultimately impact on liver function.

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This study investigated the antimicrobial and antibiofilm activity of KWI18, a new synthetic peptide. KWI18 was tested against planktonic cells and Pseudomonas aeruginosa and Candida parapsilosis biofilms. Time-kill and synergism assays were performed. Sorbitol, ergosterol, lipid peroxidation, and protein oxidation assays were used to gain insight into the mechanism of action of the peptide. Toxicity was evaluated against erythrocytes and Galleria mellonella. KWI18 showed antimicrobial activity, with minimum inhibitory concentration (MIC) values ranging from 0.5 to 10 µM. KWI18 at 10 × MIC reduced P. aeruginosa and C. parapsilosis biofilm formation and cell viability. Time-kill assays revealed that KWI18 inhibited the growth of P. aeruginosa in 4 h and that of C. parapsilosis in 6 h. The mechanism of action was related to ergosterol as well as induction of oxidative damage in cells and biofilms. Furthermore, KWI18 demonstrated low toxicity to erythrocytes and G. mellonella. KWI18 proved to be an effective antibiofilm agent, opening opportunities for the development of new antimicrobials.

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INTRODUCTION: Oxidative stress (OS) occurs in cystic fibrosis (CF). OBJECTIVE: The objective of this work is to evaluate the influence of bacterial infection on biomarkers of OS (catalase [CAT], glutathione peroxidade [GPx], reduced glutathione [GSH]), markers of oxidative damage (protein carbonyls [PC], thiobarbituric acid reactive substances [TBARS]), together with the nutritional status and lung function in children with CF. METHODS: Cross-sectional study including CF group (CFG, n = 55) and control group (CG, n = 31), median age: 3.89 and 4.62 years, respectively. CFG was distributed into CFG negative bacteriology (CFGB-, n = 27) or CFG positive bacteriology (CFGB+, n = 28), and CFG negative Pseudomonas aeruginosa (CFGPa-, n = 36) or CFG positive Pseudomonas aeruginosa (CFGPa+, n = 19). RESULTS: Compared with CG, CFG (P = .034) and CFGB+ (P = .042) had lower body mass index-for-age z-score; forced expiratory volume in the first second was lower in CFGB+ and CFGPa+ (both P < .001). After adjusting for confounders and compared with CG: CFG showed higher TBARS (P ≤ .001) and PC (P = .048), and lower CAT (P = .004) and GPx (P = .003); the increase in PC levels was observed in CFGB+ (P = .011) and CFGPa+ (P = .001) but not in CFGB- (P = .510) and CFGPa- (P = .460). CONCLUSIONS: These results indicate a systemic OS in children with CF. The presence of bacterial infection particularly Pseudomonas aeruginosa seems to be determinant to exacerbate the oxidative damage to proteins, in which PC may be a useful biomarker of OS in CF.

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PURPOSE: To evaluate the oxidative stress in swine neonates submitted to hypoxia. METHODS: Ten large white piglets, healthy newborns, of both sexes, were divided into two groups and submitted to an experimental hypoxia protocol with reduced inspired oxygen fraction. The hypoxia group, composed of six animals, was submitted to oxygen reduction for 180 min. The animals in the control group, n = 4, were handled and evaluated simultaneously, but without oxygen reduction. RESULTS: 180 min after the start of the hypoxic insult, a significant difference was observed in the oximetry, and heart rate of the hypoxia group was compared to the control group (p<0.05). There was no significant difference in the oxidative stress analyses. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (TBARS), protein carbonyl (PC), and myeloperoxidase (MPO) in the piglets' brain tissue were analyzed. CONCLUSIONS: Hypoxia causes adverse effects in swine neonates, although there is a natural physiological resistance of swine neonates to respond to this insult. Analyses of GSH, SOD, CAT, TBARS, MPO, and PC were tabulated and are presented as parameters for further studies to be carried out on an animal model of swine hypoxia.

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Acrocomia aculeata fruits are rich in monounsaturated fatty acid, ß-carotene, tocopherol, and other antioxidant compounds. The aim of our study was to investigate and compare the protective effects of A. aculeata pulp oil and microencapsulated pulp oil on brain oxidative damage induced by chronic restraint stress (CRS) in rats (cortex, hippocampus, and striatum). Thirty-six Wistar rats were divided into six treatment groups: C, P, and M groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively. The SC, SP, and SM groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively, and were then subjected to uninterrupted 6 h of CRS. After 21 days of testing, the rats were euthanized and the brain tissue of the groups was removed for evaluation for oxidative damage markers and antioxidant enzymes. Endpoints of oxidative stress (OS) markers (lipid peroxidation, protein carbonylation, and reduced glutathione [GSH]) and antioxidant enzymes (superoxide dismutase and catalase) were evaluated. By imposing chronic stress on rats, pulp oil and microcapsules of pulp oil induced positive antioxidant responses, mainly by increasing the GSH content, increasing the ability of neural tissues to deal with inherent OS, thus protecting against neurodegenerative diseases. The administration of A. aculeata pulp oil and microencapsulated pulp oil made the reversal of the oxidant parameters, which may protect the brain tissue of rats altered by CRS. The Clinical Trial Registration number: n° 1.008/2018 CEUA/UFMS.

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Metabolic syndrome (MetS) and obesity are growing in many parts of the world, becoming public health problems. It is proposed that foods with functional properties can assist in the treatment of these diseases. Crude buriti pulp oil (BPO) is a food traditionally consumed by residents in the Pantanal, Cerrado and Brazilian Amazon. It is rich in oleic acid, tocopherols and carotenoids, emerging as a potential functional food. Thus, this study aimed to evaluate the effect of the supplementation of BPO on metabolic disorders caused by a high-fat diet. Four groups of C57BL6 mice were used, a lean group with AIN-93M diet and control oil supplementation, an obese group with a high-fat diet and control oil supplementation, and two obese groups with a high-fat diet and BPO supplementation in the amounts of 50 and 100 mg/kg. BPO worsened the metabolic state caused by the high-fat diet, worsening risk factors associated with MetS, as the abdominal circumference and retroperitoneal fat, serum levels of total cholesterol, uric acid, alanine transaminase, glucose and triglycerides, and renal fat, in addition to changes in glycaemic control and oxidative stress markers. C57BL/6 mice fed with a high-fat diet and supplemented with BPO presented a worsening in metabolic risk factors associated with MetS.

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Purpose To evaluate the oxidative stress in swine neonates submitted to hypoxia. Methods Ten large white piglets, healthy newborns, of both sexes, were divided into two groups and submitted to an experimental hypoxia protocol with reduced inspired oxygen fraction. The hypoxia group, composed of six animals, was submitted to oxygen reduction for 180 min. The animals in the control group, n = 4, were handled and evaluated simultaneously, but without oxygen reduction. Results 180 min after the start of the hypoxic insult, a significant difference was observed in the oximetry, and heart rate of the hypoxia group was compared to the control group (p<0.05). There was no significant difference in the oxidative stress analyses. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (TBARS), protein carbonyl (PC), and myeloperoxidase (MPO) in the piglets’ brain tissue were analyzed. Conclusions Hypoxia causes adverse effects in swine neonates, although there is a natural physiological resistance of swine neonates to respond to this insult. Analyses of GSH, SOD, CAT, TBARS, MPO, and PC were tabulated and are presented as parameters for further studies to be carried out on an animal model of swine hypoxia.

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ABSTRACT Background: Thrombocytopenia (TP) is the major event associated with linezolid (LZD) therapy. We investigated the incidence and risk factors for thrombocytopenia in hospitalized adults who received LZD (1200 mg/day) between 2015 and 2017. HIV-positive, death during follow-up and those with a baseline platelet count ≤100 × 103/mm3 were excluded. Method: TP was defined as a decrease in platelet count of ≥20% from the baseline level at the initiation of linezolid therapy and a final count of <100 × 103/mm3. The odds ratios (OR) for thrombocytopenia were obtained using multivariate stepwise logistic regression analysis. Main results: A total of 66 patients were included (mean age [SD] 62 [18], male gender [%], 37 [56]). LZD-associated TP was identified in 12 patients (18.2%). For TP, the adjusted OR [95% CI] of the platelet count ≤200 × 103/mm3, serum creatinine and renal impairment at baseline were 5.66 [1.15-27.9], 4.57 [1.26-16.5] and 9.41 [1.09-80.54], respectively. Male gender and dosage per weight per day (DPWD) >20 mg/kg/day were not risk factors. Conclusion: The results showed that the incidence of linezolid-induced thrombocytopenia was lower in patients with normal renal function and higher in those with platelet counts ≤200 × 103/mm3 or serum creatinine >1.5 mg/dL at the start of the treatment.

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The objective of this study was to evaluate the level of genomic instability in patients with celiac disease and to establish a relationship between inflammation, oxidative stress, and DNA damage in these patients. Myeloperoxidase (MPO) activity, adenosine deaminase, nitric oxide (NOx), thiobarbituric acid, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and DNA damage were evaluated in peripheral blood samples from 47 celiac disease patients and 31 controls. Patients with celiac disease presented higher levels of DNA damage in comparison to controls (p=0.023). This difference was also observed for markers of oxidative stress, such as CAT (p=0.011) and SOD (p=0.013), and inflammatory markers such as MPO (p < 0.001) and NOx (p=0.009). Positive correlations were found between DNA damage levels and the values of CAT (r=0.405; p=0.009) and SOD (r=0.516; p < 0.001). Positive correlations were also found between GPx and NOx (r=0.349; p=0.030) and MPO and NOx (r=0.239; p=0.039). CAT and NOx showed a negative correlation (r= -0.315; p=0.042). In conclusion, intestinal inflammation can have systemic effects, causing an imbalance between oxidant and antioxidant markers, which may promote increased levels of DNA damage.

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PURPOSE: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. METHODS: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. RESULTS: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. CONCLUSIONS: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

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BACKGROUND: Thrombocytopenia (TP) is the major event associated with linezolid (LZD) therapy. We investigated the incidence and risk factors for thrombocytopenia in hospitalized adults who received LZD (1200mg/day) between 2015 and 2017. HIV-positive, death during follow-up and those with a baseline platelet count ≤100×103/mm3 were excluded. METHOD: TP was defined as a decrease in platelet count of ≥20% from the baseline level at the initiation of linezolid therapy and a final count of <100×103/mm3. The odds ratios (OR) for thrombocytopenia were obtained using multivariate stepwise logistic regression analysis. MAIN RESULTS: A total of 66 patients were included (mean age [SD] 62 [18], male gender [%], 37 [56]). LZD-associated TP was identified in 12 patients (18.2%). For TP, the adjusted OR [95% CI] of the platelet count ≤200×103/mm3, serum creatinine and renal impairment at baseline were 5.66 [1.15-27.9], 4.57 [1.26-16.5] and 9.41 [1.09-80.54], respectively. Male gender and dosage per weight per day (DPWD) >20mg/kg/day were not risk factors. CONCLUSION: The results showed that the incidence of linezolid-induced thrombocytopenia was lower in patients with normal renal function and higher in those with platelet counts ≤200×103/mm3 or serum creatinine >1.5mg/dL at the start of the treatment.

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Several reports have shown the presence of P2 receptors in hematopoietic stem cells (HSCs). These receptors are activated by extracellular nucleotides released from different sources. In the hematopoietic niche, the release of purines and pyrimidines in the milieu by lytic and nonlytic mechanisms has been described. The expression of P2 receptors from HSCs until maturity is still intriguing scientists. Several reports have shown the participation of P2 receptors in events associated with modulation of the immune system, but their participation in other physiological processes is under investigation. The presence of P2 receptors in HSCs and their ability to modulate this population have awakened interest in exploring the involvement of P2 receptors in hematopoiesis and their participation in hematopoietic disorders. Among the P2 receptors, the receptor P2X7 is of particular interest, because of its different roles in hematopoietic cells (e.g., infection, inflammation, cell death and survival, leukemias and lymphomas), making the P2X7 receptor a promising pharmacological target. Additionally, the role of P2Y12 receptor in platelet activation has been well-documented and is the main example of the importance of the pharmacological modulation of P2 receptor activity. In this review, we focus on the role of P2 receptors in the hematopoietic system, addressing these receptors as potential pharmacological targets.

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