Drugs in R&D · 2014
Assessment of anti-plasmodial activity of non-hemolytic, non-immunogenic, non-toxic antimicrobial peptides (AMPs LR14) produced by Lactobacillus plantarum LR/14.
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Gupta Ruchi, Rajendran Vinoth, Ghosh Prahlad C, Srivastava Sheela
Аннотация
BACKGROUND AND OBJECTIVES: Lactobacillus plantarum strains are known to exhibit an antimicrobial property against bacteria and fungi. In the present investigation, AMPs LR14, antimicrobial peptides produced by L. plantarum strain LR/14, were tested against a protozoan system, Plasmodium falciparum and its non-toxic nature was envisaged on a mammalian system.
METHODS: Human erythrocytes infected with chloroquine-sensitive and -resistant strains of P. falciparum were treated with purified AMPs LR14. The loss in cell viability was assessed by monitoring the incorporation of [(3)H]-hypoxanthine in the nucleic acid of the parasite. The hemolytic activity of AMPs LR14 was monitored at different concentrations and the investigations into the in vivo toxicity of AMPs LR14 were carried out on a mammalian system (Wistar rat). The level of toxicity in the tissues was visualized by histopathological studies conducted on the liver and kidney of the test and control rats. A study was also undertaken to see the production of antibodies in an animal (rabbit) after it was immunized with AMPs LR14.
RESULTS: A loss in cell viability was observed in both test strains of P. falciparum. However, the dose required for inhibition of the chloroquine-resistant strain was ~2 times the dose required for the chloroquine-sensitive strain. At these concentrations, no hemolysis of human erythrocytes was observed. The studies conducted on in vivo toxicity of AMPs LR14 suggest that the lethal dose (LD50) is beyond 1,000 mg/kg body weight, suggesting its safe use against microbes and protozoans. Antibodies were also not detected against these peptides, indicating a non-immunogenic nature.
CONCLUSION: The data indicate that AMPs LR14 are non-toxic, potent anti-plasmodial peptides causing growth inhibition of P. falciparum without causing hemolysis. These results pave the way for the development of bioactive peptides as therapeutics.
METHODS: Human erythrocytes infected with chloroquine-sensitive and -resistant strains of P. falciparum were treated with purified AMPs LR14. The loss in cell viability was assessed by monitoring the incorporation of [(3)H]-hypoxanthine in the nucleic acid of the parasite. The hemolytic activity of AMPs LR14 was monitored at different concentrations and the investigations into the in vivo toxicity of AMPs LR14 were carried out on a mammalian system (Wistar rat). The level of toxicity in the tissues was visualized by histopathological studies conducted on the liver and kidney of the test and control rats. A study was also undertaken to see the production of antibodies in an animal (rabbit) after it was immunized with AMPs LR14.
RESULTS: A loss in cell viability was observed in both test strains of P. falciparum. However, the dose required for inhibition of the chloroquine-resistant strain was ~2 times the dose required for the chloroquine-sensitive strain. At these concentrations, no hemolysis of human erythrocytes was observed. The studies conducted on in vivo toxicity of AMPs LR14 suggest that the lethal dose (LD50) is beyond 1,000 mg/kg body weight, suggesting its safe use against microbes and protozoans. Antibodies were also not detected against these peptides, indicating a non-immunogenic nature.
CONCLUSION: The data indicate that AMPs LR14 are non-toxic, potent anti-plasmodial peptides causing growth inhibition of P. falciparum without causing hemolysis. These results pave the way for the development of bioactive peptides as therapeutics.