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JP Ganley, D Chen, MP Langford; Clearance of Cytotoxic Bacterial Cell Wall Component (Muramyl Dipeptide) from Rabbit Aqueous and Blood . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2249.
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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.
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