The mechanism of cadmium-induced lysozyme enhancement in rabbit kidney

Abstract

The effect of cadmium on the renal lysozyme level was examined by injecting male albino rabbits subcutaneously with 1 mg cadmium/kg body weight three times a week for 1 or 3 months. The lysozyme level in the renal brush border membrane of the cadmium-treated animals was elevated ten-fold. The lysozyme activity in the liver and small intestine tissue homogenates of rabbits was elevated by a 1-month treatment with cadmium, markedly elevated in the kidney, but markedly reduced in the spleen and lungs. Exposure to cadmium for 3 months produced an essentially similar effect on the enzyme level in the tissue, except for the lungs in which the lysozyme level returned to the preinjection level. This marked increase in the lysozyme level in the kidney of cadmium-treated rabbits was confirmed by an indirect immunofluorescent antibody technique. In control animals, intracellular distribution of the enzyme was selectively distributed to only a small number of proximal tubules, with none distributed in the medulla or glomerulus. However, after expose to cadmium, the renal tubules showed strongly positive lysozyme staining. In addition to an increase in intensity of the specific fluorescence, this enzyme was widely distributed not only in the proximal convoluted portion, but also in the straight portion of the proximal tubules, which essentially showed no enzyme activity under normal conditions. The enzyme in these cells was evenly distributed throughout the cytoplasm. The plasma lysozyme level increased immediately after the administration of cadmium, and detectable amounts of the enzyme began to appear in urine from the 3rd week after the first injection, with a 1-week lag after the maximum level of lysozyme in the plasma. This high level of plasma lysozyme, varied two-to four-fold over the control, and lysozymuria continued throughout the experiment. The concentration of cadmium in the renal cortex was 141 micrograms/g wet tissue at 1 month, and 208 micrograms at 3 months. In conclusion, the cadmium-induced enhancement of the lysozyme level in the renal cortex may be due primarily to the elevation of the lysozyme level in plasma by cadmium. The enzymatic high net positive charge, characteristic of lysozyme, may contribute greatly to this mechanism. In addition, the excretion of a large amount of lysozyme into the urine observed in a later stage may be due to the concomitant occurrence of leakage from the destroyed tubular cells and reduced tubular reabsorption of filtered enzyme, whereas lysozymuria at an early stage may be solely due to excess amounts of plasma lysozyme.