Abstract
Nu-3 [butyl-phosphate-5′-thymidine-3′-phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria including Pseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an LD50 of 2001mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.
Highlights
Pseudomonas aeruginosa has become the most common gram-negative bacterial species associated with serious hospital-acquired infections [1, 2]
To provide clinicians with credible alternative treatments to reduce the increasing human mortality and morbidity associated with the infectious diseases by drug-resistant bacterial pathogens, there is a compelling need to develop new therapeutic agents that are effective against drug-resistant mutants [10]
The healthcare community is desperate for new therapeutics
Summary
Pseudomonas aeruginosa has become the most common gram-negative bacterial species associated with serious hospital-acquired infections [1, 2]. Immediate use of effective antimicrobial therapy for P. aeruginosa bacteremia has been shown to significantly reduce mortality [4]. The intrinsic resistance of P. aeruginosa to many antimicrobial agents and, in addition, the variety of their increasingly recognized acquired resistance mechanisms make their management in the hospital setting problematic [5]. The development of new antibiotics with activity against gram-negative organisms has not kept pace with the increase in prevalence of multidrug resistant pathogens. To provide clinicians with credible alternative treatments to reduce the increasing human mortality and morbidity associated with the infectious diseases by drug-resistant bacterial pathogens, there is a compelling need to develop new therapeutic agents that are effective against drug-resistant mutants [10]
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