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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

Histopathological observation of Nu-3 treated mice. (a) Livers from the control group. (b) Livers from the Nu1-3 treated group. The hepatic structure is normal no histopathological changes were observed. Original magnification ×400.
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fig2: Histopathological observation of Nu-3 treated mice. (a) Livers from the control group. (b) Livers from the Nu1-3 treated group. The hepatic structure is normal no histopathological changes were observed. Original magnification ×400.

Mentions: Mice were intragastrically administered with a single dose of Nu-3 at 2500 (Group 1), 1988 (Group 2), 1580 (Group 3), 1256 (Group 4), and 1000 (Group 5) mg/kg/mouse (Table 1). Following the single dose, five male and four female mice in Group 1, four female in Group 2 died in 24 hours. One female in Group 2 and one female in Group 4 died on day 1. From day 2 to day 8 none of the mice in all the groups died. According to the mortality of each group, the minimum lethal dose (MLD) was calculated to be 1256 mg/kg. Clinical observations of the dying mice attributed to the administration of Nu-3 were lethargy, tachypnea, and tremor and disheveled clothing hair. The surviving mice did not show any evident toxic symptom in clinical observations. There were no treatment-related effects on mouse behavior in the cage and body weight for males or females (data not shown). In the early dead mice, some pathological changes were found, including livers turning white and brittle with some yellowish brown nidi, the change of the spleen surface into uneven with some hemorrhagic spots, and kidneys showing some gray-white focus on surfaces. It was also observed that there were some damages and hemorrhage in gastric walls and intestinal tracts of mice which died in 5 hours after being administered. There was no obvious pathological change at gross necropsy and histopathological changes in liver for scheduled euthanasia mice in the study (Figure 2).


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)

Histopathological observation of Nu-3 treated mice. (a) Livers from the control group. (b) Livers from the Nu1-3 treated group. The hepatic structure is normal no histopathological changes were observed. Original magnification ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Histopathological observation of Nu-3 treated mice. (a) Livers from the control group. (b) Livers from the Nu1-3 treated group. The hepatic structure is normal no histopathological changes were observed. Original magnification ×400.
Mentions: Mice were intragastrically administered with a single dose of Nu-3 at 2500 (Group 1), 1988 (Group 2), 1580 (Group 3), 1256 (Group 4), and 1000 (Group 5) mg/kg/mouse (Table 1). Following the single dose, five male and four female mice in Group 1, four female in Group 2 died in 24 hours. One female in Group 2 and one female in Group 4 died on day 1. From day 2 to day 8 none of the mice in all the groups died. According to the mortality of each group, the minimum lethal dose (MLD) was calculated to be 1256 mg/kg. Clinical observations of the dying mice attributed to the administration of Nu-3 were lethargy, tachypnea, and tremor and disheveled clothing hair. The surviving mice did not show any evident toxic symptom in clinical observations. There were no treatment-related effects on mouse behavior in the cage and body weight for males or females (data not shown). In the early dead mice, some pathological changes were found, including livers turning white and brittle with some yellowish brown nidi, the change of the spleen surface into uneven with some hemorrhagic spots, and kidneys showing some gray-white focus on surfaces. It was also observed that there were some damages and hemorrhage in gastric walls and intestinal tracts of mice which died in 5 hours after being administered. There was no obvious pathological change at gross necropsy and histopathological changes in liver for scheduled euthanasia mice in the study (Figure 2).

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