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Acute, multiple-dose dermal and genetic toxicity of Nu-3: a novel antimicrobial agent.

Sun J, Hu Y, Cao S, Zhang G, Sun LQ, Wang M - J. Biomed. Biotechnol. (2010)

Bottom Line: However, data on the toxicological profile of Nu-3 are still lacking.The acute oral toxicity test in mice showed that Nu-3 had an LD(50) of 2001 mg/kg body weight.Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, China Agricultura University, Beijing 100193, China.

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 LD(50) of 2001 mg/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.

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Related in: MedlinePlus

Clinical observations after repeated dermal doses of Nu-3 for 28 days. (a) Body weight; (b) water uptake; (c) food uptake.
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Related In: Results  -  Collection


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fig4: Clinical observations after repeated dermal doses of Nu-3 for 28 days. (a) Body weight; (b) water uptake; (c) food uptake.

Mentions: Rats were applied with 50 μl of 100 mg/ml Nu-3 (total dose of 250 mg/kg/day) for 28 days. Cage side observation was made twice everyday. There were no evident toxic symptoms in both treated and control rats during observation time. Local dermal irritation was not observed in all test rats. Control and test rats showed a similar pattern of weight growth, food and water uptake (Figure 4). Although there seemed to be some lagging in water uptake in treated group compared to control (Figure 4(b)), the body weight of test group seemed to increase faster (Figure 4(a)). There were no treatment-related changes on food uptake in treated rats compared to the controls (Figure 4(c)). During the observation time after administrating Nu-3 on the back of the body for 28 days, there were no significant differences between the treated and control rats in the body weight gain although the treated rats took less water and food compared to the controls.


Acute, multiple-dose dermal and genetic toxicity of Nu-3: a novel antimicrobial agent.

Sun J, Hu Y, Cao S, Zhang G, Sun LQ, Wang M - J. Biomed. Biotechnol. (2010)

Clinical observations after repeated dermal doses of Nu-3 for 28 days. (a) Body weight; (b) water uptake; (c) food uptake.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2914288&req=5

fig4: Clinical observations after repeated dermal doses of Nu-3 for 28 days. (a) Body weight; (b) water uptake; (c) food uptake.
Mentions: Rats were applied with 50 μl of 100 mg/ml Nu-3 (total dose of 250 mg/kg/day) for 28 days. Cage side observation was made twice everyday. There were no evident toxic symptoms in both treated and control rats during observation time. Local dermal irritation was not observed in all test rats. Control and test rats showed a similar pattern of weight growth, food and water uptake (Figure 4). Although there seemed to be some lagging in water uptake in treated group compared to control (Figure 4(b)), the body weight of test group seemed to increase faster (Figure 4(a)). There were no treatment-related changes on food uptake in treated rats compared to the controls (Figure 4(c)). During the observation time after administrating Nu-3 on the back of the body for 28 days, there were no significant differences between the treated and control rats in the body weight gain although the treated rats took less water and food compared to the controls.

Bottom Line: However, data on the toxicological profile of Nu-3 are still lacking.The acute oral toxicity test in mice showed that Nu-3 had an LD(50) of 2001 mg/kg body weight.Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, China Agricultura University, Beijing 100193, China.

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 LD(50) of 2001 mg/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.

Show MeSH
Related in: MedlinePlus