Lack of toxicity of oral and intrapulmonary group B streptococcal lipoteichoic acid.
Lipoteichoic acid (LTA) was prepared from type III group B streptococci and administered by topical oral application or intravenous or intratracheal injection in weanling and adult white New Zealand rabbits. Tritiated [3H]LTA in tissues and body fluids was measured by scintillation spectrometry. Five minutes to 120 h after intravenous injection of 10 mg (17 x 10(6) dpm) of [3H]LTA, none was present in blood. Combined urine and fecal excretion peaked at 24 h and decreased over 5 days. There was no effect on collagen-induced platelet aggregation. [3H]LTA concentrations were greatest in colon, bone, stomach, and skin 1 day after intravenous injection. After a 5-mg oral dose (8.5 x 10(6) dpm) in an adult animal, fecal excretion peaked at 24 h and decreased after 4 days. No systemic absorption was noted. No [3H]LTA was found in any of seven tissues examined at autopsy 3 days after 1 to 5 mg/kg oral doses in weanling animals with normal or traumatized buccal mucosa. No effect was noted on platelet aggregation or serum complement, there was no increase in the incidence of nephrocalcinosis and the buccal mucosa remained histologically normal. Intratracheal injection of 0.5 to 2.5 mg/kg of LTA resulted in no tachypnea or alteration in blood gases. All animals remained healthy after LTA administration. The absence of toxicity and absorption in animals suggests that studies could be performed in humans to evaluate the safety and efficacy of oral LTA.
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D002610:Cheek; D003176:Complement C3 / Q000378:metabolism; D005243:Feces / Q000032:analysis; D005260:Female; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000473:pathology; D009397:Nephrocalcinosis / Q000139:chemically induced; D010712:Phosphatidic Acids / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity* / Q000652:urine; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013292:Streptococcus agalactiae; D013682:Teichoic Acids / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity* / Q000652:urine; D013997:Time Factors; D014018:Tissue Distribution
D003176:Complement C3; D008070:Lipopolysaccharides; D010712:Phosphatidic Acids; D013682:Teichoic Acids; C009900:lipoteichoic acid