The distribution kinetics of topical 14C-sulfur mustard in rabbit ocular tissues and the effect of acetylcysteine

Sulfur mustard (2,2-dichlorodiethyl sulfide; HD), is a potent alkylating agent which in liquid or vapor form is capable of causing severe injuries to skin and respiratory tract, and was shown to cause short- and long-term ocular injuries. N-Acetylcysteine (NAC) may act as a mucolytic agent, changing the "wetting" and scavenging properties of the cornea and thus the adhesion of HD. Moreover, NAC is a scavenger of HD, an antioxidant and a glutathione precursor, which was shown to reduce HD toxicity in various systems. The ocular distribution of C-14, after topical application of liquid C-14- sulfur mustard (C-14-HD) to the rabbit cornea, and the role of NAC in reducing HD retention and toxicity are presented in this study. Groups of rabbits were exposed to 0.4 muL of liquid C-14-HD, placed at the center of the cornea, with or without NAC treatment. Fifty muL NAC (10% aqueous solution) was topically applied, 10 minutes before and 10 minutes after HD exposure. Three time points were evaluated: 1, 6, and 24 hr after HD exposure, six rabbits per time point. Evaluation consisted of clinical observation, measurement of biochemical parameters in aqueous humor (AQ), counting radioactivity concentration in ocular tissues, and histology of corneal sections. One hour after corneal exposure to liquid C-14-HD, approximately 2% of total applied radioactivity was recovered. The highest C-14 concentration was found in the cornea, followed by the tarsal section of eyelid, aqueous humor, nictitating membrane, and the frontal sclera (including conjunctiva). The rate of radioactivity decrease varied from one ocular tissue to the other, the highest rate was found in aqueous and vitreous humors, also in accordance with their higher turnover rates. The NAC treatment reduced the radioactivity in most ocular tissues. The HD exposure caused typical clinical and histological signs of HD intoxication, and increased the aqueous protein and prostaglandin (PGE) content. The NAC treatment lowered eyelid edema but had no effect on AQ protein or PGE content; however, there was some aggravating effect of the NAC treatment on corneal epithelial cells, seen at 1 and 6 hr after exposure.