Abstract
Abstract: :
We have noted the cytotoxic/apoptogenic activity of the synthetic bacterial cell wall component, muramyl dipeptide (MDP; N-acetyl muramyl L-alanyl-D-isoglutamine) in rabbit renal cells. Purpose: Using the rabbit renal cell bioassay, we investigate the clearance of MDP from the rabbit aqueous after intracameral (i.c.) injection and from the blood after intravenous (i.v.) injection. Methods: Aqueous samples were collected from adult rabbits at 0.5, 1, 2, 3, and 6 h post i.c. injection with 50 mg/0.05 ml MDP. Tear, blood and urine samples were collected from 4 two yr-old rabbits given i.v. MDP (1 mg/kg). The levels of MDP induced cytotoxicity (CD50/ml) was determined by bioassay. Results: The levels of MDP-induced toxicity rapidly decreased to undetectable levels by 6 h with ≷90% reduction in MDP within 3 h post i.v. MDP injection. MDP was detected in tear fluid up to 2 h post i.v. injection. Conjunctivitis and anterior uveitis was detected at 1-2 h post i.v. injection. Blood levels of MDP became undetectable in 3 of 4 rabbits by 6 h. In 2 rabbits the MDP (≷90%) was detected in urine within 24. However, the other 2 rabbits only cleared 56% and 75% of the injected the MDP and died at 5 and 7 d post injection, respectively. Conclusions: MDP is rapidly cleared from the anterior chamber and from blood by the kidney and most is excreted. Our results indicate that rabbits that failed to clear the MDP died.
Keywords: 328 bacterial disease • 612 uveitis-clinical/animal model • 469 microbial pathogenesis: experimental studies