In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium

BPP-BrachyNH2 is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog Brachycephalus ephippium, which possess in vitro inhibitory activity of angiotensin-I converting enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH2. The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH2 induced high predicted LD50 values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH2 at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH2, leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.info:eu-repo/semantics/publishedVersio

Mechanical Periodontal Therapy Recovered the Phagocytic Function of Monocytes in Periodontitis

Background. Several studies have focused on the association between periodontitis and systemic implications; however, the biological mechanisms of the immune responses before and after periodontal therapy involved in this relationship, such as phagocytic functions, remain unclear. Objectives. This study aimed to investigate whether periodontal treatment improves the phagocytic function of blood monocytes in patients with severe periodontitis. Materials and Methods. A nonrandomized sample of 55 participants was enrolled in the study. Two groups were studied: control (n = 27, healthy subjects without periodontal disease) and patients (n = 28, individuals with periodontitis). Treatment of periodontitis (scaling and root planing) was performed until the clinical resolution of periodontal pockets and inflammation. The following clinical periodontal parameters were assessed: probing depth, clinical attachment level, visible plaque index (PI), and gingival bleeding on probing index before and after mechanical periodontal treatment. The phagocytic index (PhI) and nitro blue tetrazolium test (NBT) were assessed before and immediately after the end of treatment. Results. Periodontitis induced impaired phagocytosis by monocytes. Phagocytosis at baseline was significantly lower in periodontitis patients [median, 13.2 (range of 7.1 to 20.8) and 60.7 (40.6 to 88.6)] than in controls [27.4 (15.5 to 40.5)] and 98 (68.2 to 122.9)] for nonsensitized or sensitized samples, respectively. After supportive therapy, patients showed a significant enhancement of phagocytic functions [33.7 (14.6 to 53.2) and 108.5 (99.6 to 159.5)] for nonsensitized and sensitized samples, respectively. Periodontal treatment increased the phagocytic capacity to a level similar to that observed in the control group and improved the capacity of phagocytes to produce superoxide anion. Conclusions. The results suggest that periodontal therapy in patients with severe periodontitis provides a state of homeostasis due to the reestablishment of phagocytic function and increased production of NBT (Regional Registry No. RBR-24T799; Universal Registry No. U1111-1133-5512)

Anthelmintic Activity In Vivo of Epiisopiloturine against Juvenile and Adult Worms of Schistosoma mansoni

Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds. This work reports the in vivo effect of the alkaloid epiisopiloturine (EPI) against adults and juvenile worms of Schistosoma mansoni. EPI was first purified its thermal behavior and theoretical solubility parameters charaterised. In the experiment, mice were treated with EPI over the 21 days post-infection with the doses of 40 and 200 mg/kg, and 45 days post-infection with single doses of 40, 100 and 300 mg/kg. The treatment with EPI at 40 mg/kg was more effective in adult worms when compared with doses of 100 and 300 mg/kg. The treatment with 40 mg/kg in adult worms reduced parasite burden significantly, lead to reduction in hepatosplenomegaly, reduced the egg burden in faeces, and decreased granuloma diameter. Scanning electron microscopy revealed morphological changes to the parasite tegument after treatment, including the loss of important features. Additionally, the in vivo treatment against juvenile with 40 mg/kg showed a reduction of the total worm burden of 50.2%. Histopathological studies were performed on liver, spleen, lung, kidney and brain and EPI was shown to have a DL50 of 8000 mg/kg. Therefore EPI shows potential to be used in schistosomiasis treatment. This is the first time that schistosomicidal in vivo activity of EPI has been reported