magainin-2-peptide--xenopus and Disease-Models--Animal

Due to emergence of multidrug resistance in pathogens, the attention of the scientific community is now directed towards strengthening the reservoir of antimicrobial compounds. Prior to in vivo studies, the interaction and penetration of a hybrid peptide K11 in bacterial cells using confocal microscopy was assessed which was observed as early as 10 min after incubation with the peptide. Cell lysis along with leakage of cytoplasmic content was confirmed by electron microscopy. To evaluate the in vivo performance of the peptide, it was contained in carbopol hydrogel. Efficacy of the hydrogel formulation was then evaluated against Acinetobacter baumannii-infected wounds using a murine excision model. Treatment resulted in restoration of body weight, complete clearance of infection from the wound by day 7 and 99% wound enclosure by day 21, in contrast to the persistence of infection and 70% wound enclosure in the infected group. Further, this treatment resulted in a 2.6-fold decrease in the levels of malondialdehyde along with a 4.5-fold increase in the levels of catalase on day 3. Appearance of normal histo-architecture was observed in the treatment group. Based on these results, the peptide hydrogel can be exploited in future as one of the strategies for developing a topical anti-infective therapeutic agent.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Disease Models, Animal; Hydrogel, Polyethylene Glycol Dimethacrylate; Magainins; Melitten; Mice; Microscopy, Confocal; Microscopy, Electron; Recombinant Fusion Proteins; Time Factors; Treatment Outcome; Wound Healing; Wound Infection; Xenopus Proteins

Topics: Amphibian Proteins; Animals; Anti-Infective Agents; Antimicrobial Cationic Peptides; Bacterial Translocation; Bile Ducts; Disease Models, Animal; Endotoxins; Jaundice, Obstructive; Magainins; Penicillanic Acid; Peptides; Piperacillin; Rats; Tazobactam; Xenopus Proteins

The therapeutic efficacies of three polycationic peptides selected among the class of the magainins (magainin I, magainin II, and magainin II amide), alone and combined with piperacillin, were investigated in a rat model of septic shock. Rats were given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli and randomized to receive intraperitoneally isotonic sodium chloride solution, 60 mg of piperacillin per kg of body weight, and 1 mg of each magainin per kg alone and combined with 60 mg of piperacillin per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatments with the magainins achieved significant reductions of bacterial growth and plasma endotoxin and TNF-alpha concentrations. In general, treatments with the combinations of magainins and piperacillin demonstrated the highest efficacies.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Disease Models, Animal; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Infusions, Parenteral; Magainins; Male; Microbial Sensitivity Tests; Piperacillin; Rats; Rats, Wistar; Shock, Septic; Treatment Outcome; Xenopus Proteins

Linear helical channel-forming peptides structurally similar to the Xenopus-derived antibiotic, Magainin2-amide, were synthesized. Because activity resides in the physicochemical properties of the peptides, an all-D-amino acid as well as an all-L-amino acid sequence were tested for anticancer activity. In vitro activity against carcinoma cells and in vivo efficacy against four murine ascites tumors were determined. The novel peptides proved to have enhanced potency in vitro and in vivo as compared to the parent compound. The 50% inhibitory concentrations against A549 cells for the all-D, the all-L, and Magainin2 were 6, 10, and 110 micrograms/ml, respectively. All three peptides had activity against P388 leukemia, S180 ascites, and a spontaneous ovarian tumor when injected i.p. Increase in life span of over 100% was produced for the analogues in the latter two models. The maximally effective concentrations for the analogues were 20 to 25 mg/kg while Magainin2 required 50-60 mg/kg for in vivo efficacy. The all-D-amino acid peptide, MSI-238, proved as effective as doxorubicin at a more advanced stage of the ovarian tumor and this activity may be attributed to its resistance to proteolytic degradation. Therefore, this class of amphiphilic alpha-helical cationic peptides has potential in the peritoneal treatment of ovarian cancer.

Topics: Amino Acid Sequence; Animals; Antimicrobial Cationic Peptides; Antineoplastic Agents; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; Leukemia L1210; Leukemia P388; Magainins; Male; Mice; Mice, Inbred DBA; Molecular Sequence Data; Neoplasms, Experimental; Ovarian Neoplasms; Peptides; Peritoneal Neoplasms; Sarcoma 180; Teratoma; Xenopus Proteins