Aims: Dinoponera quadriceps venom (DqV) was examined to evaluate the antibacterial activity and its bactericidal action mechanism against Staphylococcus aureus. Methods and Results: DqV was tested against a standard strain of methicillinsensitive Staphylococcus aureus (MSSA), Staph. aureus ATCC 6538P and two standard strains of methicillin-resistant Staphylococcus aureus (MRSA), Staph. aureus ATCC 33591 and Staph. aureus CCBH 5330. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the rate of kill and pH sensitivity of the DqV were determined by microdilution tests. Bactericidal and inhibitory concentrations of DqV were tested to check its action on Staph. aureus membrane permeability and cell morphology. The MIC and MBC of DqV were 6Á25 and 12Á5 lg ml À1 forStaph. aureus ATCC 6538P, 12Á5 and 50 lg ml À1 for Staph. aureus CCBH 5330 and 100 and 100 lg ml À1 for Staph. aureus ATCC 33591, respectively.Complete bacterial growth inhibition was observed after 4 h of incubation with the MBC of DqV. A lowest MIC was observed in alkaline pH. Alteration in membrane permeability was observed through the increase in crystal violet uptake, genetic material release and morphology in atomic force microscopy. Conclusions:The results suggest antibacterial activity of DqV against Staph. aureus and that the venom acts in the cell membrane. Significance and Impact of the Study: Alteration in membrane permeability may be associated with the antimicrobial activity of hymenopteran venoms.

Chagas' disease is a neglected disease caused by the protozoan parasite Trypanosoma cruzi and constitutes a serious health problem worldwide. The treatment is limited, with variable efficacy of benznidazole and nifurtimox. Betulinic Acid (BA), a triterpene, can be found in medicinal herbs and has a wide variety of biological and pharmacological activities. The objective was to evaluate betulinic acid effects on the cell death mechanism in Trypanosoma cruzi strain Y. BA inhibited the growth of epimastigotes in periods of 24h (IC=73.43μM), 48h (IC=119.8μM) and 72h (IC=212.2μM) of incubation; of trypomastigotes (IC=51.88μM) in periods of 24h and intracellular amastigotes (IC=25.94μM) in periods of 24 and 48h of incubation, no toxicity on LLC-MK cells at the concentrations used. Analysis of the possible mechanism of parasite cell death showed alterations in mitochondrial membrane potential, alterations in cell membrane integrity, an increase in the formation of reactive oxygen species and increase swelling of the reservosomes. In conclusion, betulinic acid was be able to inhibition all developmental forms of Trypanosoma cruzi Y strain with necrotic mechanism and involvement of mitochondrial membrane potential alteration and increase in reactive oxygen species.

Acute kidney injury (AKI) is one of the most important complications of bothropic poisoning and its early identification remains challenging. The nephrotoxicity of Bothrops insularis venom (BinsV) was previously described by our research group. In this study, we continued to evaluate the effect of BinsV on kidney function in mice and LLC-MK2 proximal tubule cells, evaluating KIM-1 protein as an early AKI biomarker. Male Swiss mice were inoculated with BinsV intramuscularly and observed for 24 h in a metabolic cage model. Urine and blood were collected for biochemical analyses and the kidneys were examined for oxide-reducing balance and submitted to histological analysis. LLC-MK2 cells incubated with BinsV were assessed for cell viability and cell death mechanism by flow cytometry. Histological analysis of the kidneys indicated AKI and the oxide-reducing analyses demonstrated a decreasing in reduced glutathione (GSH) levels and an increasing on Malondialdehyde (MDA) levels. BinsV was cytotoxic to LLC-MK2 and the cytometry analyses suggested necrosis. Within 24 h after the envenomation, urinary creatinine did not increase, but the urinary levels of KIM-1 increased. In conclusion, we found AKI evidence in the kidney tissue and the increase in the KIM-1 levels suggest it can be used as an early AKI biomarker.

Aims: Violacein (VIO), a bacterial pigment produced by Chromobacterium violaceum, was examined to evaluate the antichagasic activity and its action mechanism against Trypanosoma cruzi Y strain. Methods and Results: Violacein was tested against the epimastigote, trypomastigote and amastigote forms of T. cruzi Y strain (benznidazoleresistant strain). VIO inhibited all T. cruzi developmental forms, including amastigotes, which is implicated in the burden of infection in the chronic phase of Chagas disease (CD). VIO induced cell death in T. cruzi through apoptosis, as determined by flow cytometry analyses with specific molecular probes and morphological alterations, such as involvement of reactive oxygen species and changes in mitochondrial membrane potential and cell shrinkage. Conclusion: The results suggest antichagasic activity of VIO against T. cruzi Y strain with apoptotic involvement. Significance and Impact of the Study: The treatment of CD has limited efficacy and side effects that restrict patient tolerability and compliance. The VIO molecule could be used as a model for therapeutic alternatives for this disease.

Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid HIGHLIGHTS  Ischemia-reperfusion triggers acute kidney injury due to reactive oxygen species. Quercetin is an antioxidant flavonoid that modulate the Rennin-Angiotensin System. Quercetin prevents tubular cell death, oxidation, and mitochondrial depolarization. Quercetin interacts with the angiotensin AT1 receptor.2 Canuto, J.A.; et al.