Transport and toxicity of methylmercury along the proximal tubule of the rabbit.

Toxicity and transport of methylmercury were studied in isolated perfused S1, S2, and S3 segments of the renal proximal tubule of the rabbit. Methylmercury (II) chloride, ranging from 1 nM-1 mM, was perfused through the lumen of the three segments for up to 60 min. Lumen-to-bath transport of methylmercury was studied when the concentration of methylmercury in the perfusing solution was 18.4 microM. S1 segments of the proximal tubule were most vulnerable to the toxic effects of methylmercury. Cellular swelling and blebbing occurred when the concentration of methylmercury in the perfusate was as low as 1 nM. In the S2 and S3 segments, morphologically discernable cellular injury did not occur until the concentration of methylmercury in the perfusate was greater than 100 nM. Due to severe cellular injury and luminal occlusion, transport data could not be obtained from S1 segments. However, transport could be measured in both S2 and S3 segments. Methylmercury (18.4 microM) disappeared from the luminal fluid across the luminal membrane (JD) very rapidly in both segments. The rate was so rapid that about 80% of the methylmercury that entered the luminal fluid was abstracted. Interestingly, the rate at which mercury appeared in the bathing solution (JA) was statistically equivalent to the JD. Since the predicted leak of methylmercury was very low, most of the JA represented actual transepithelial flux of methylmercury. When 80 microM glutathione (GSH) was added to the perfusate along with 18.4 microM methylmercury, the JD was decreased significantly in both S2 and S3 segments. Moreover, the addition of 80 microM GSH caused cellular injury to be exacerbated in the S3 segments. In conclusion, there are differences in the toxicity of methylmercury along the three segments of the proximal tubule when the methylmercury is delivered to the lumen of the segments in a simple electrolyte solution. Methylmercury is very avidly transported across the tubular epithelium in S2 and S3 segments of the proximal tubule. In addition, when 80 microM GSH is added to the perfusate, the toxicity and transport of methylmercury are modified.