Acute, multiple-dose dermal and genetic toxicity of Nu-3: a novel antimicrobial agent.
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.
Sun
Juan
J
College of Veterinary Medicine, China Agricultura University, Beijing 100193, China.
Hu
Yanxin
Y
Cao
Shanping
S
Zhang
Guozhong
G
Sun
Lun-Quan
LQ
Wang
Ming
M
D000704:Analysis of Variance; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000633:toxicity*; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005123:Eye / Q000187:drug effects; D005260:Female; D006651:Histocytochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D009092:Mucous Membrane / Q000187:drug effects; D009152:Mutagenicity Tests / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects; D023422:Skin Irritancy Tests / Q000379:methods; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects; D013938:Thymidine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D013942:Thymine Nucleotides / Q000008:administration & dosage / Q000633:toxicity*; D023382:Toxicity Tests, Acute / Q000379:methods*
D000890:Anti-Infective Agents; D013942:Thymine Nucleotides; C554546:butyl-phosphate-5'-thymidine-3'-phosphate-butyl; D013938:Thymidine Monophosphate