Cadmium toxicity in primary cultures of rat hepatocytes

Primary cultures of rat hepatocytes served as an experimental model to evaluate the cytotoxicity of cadmium chloride. Cellular injury was assessed by a series of enzymatic and functional indices in 24-h-old cultures exposed for 1 h to concentrations of cadmium chloride ranging from 50 to 400 muM. In cultures that were evaluated immediately after the 1-h exposure to cadmium, little evidence of toxicity was observed as evaluated by total cellular protein content and cell viability. In similarly treated cultures, leakage of lactate dehydrogenase from the hepatocytes into the culture medium was increased in a dose-dependent manner. The most sensitive indicators of cadmium toxicity proved to be two parameters of metabolic activity: lactate-to-pyruvate (L/P) ratios, and intracellular levels of urea. Cadmium exposure produced substantial increases in L/P ratios and decreases in urea content in the cultured liver cells. If the cultures were allowed to recover by replacing the cadmium-containing medium after 1 h of exposure with fresh medium for 24 h, cellular protein content and cell viability were shown to decrease by 40%. These findings indicate that measures of metabolic integrity of cultured hepatocytes are more sensitive indices of early cadmium cytotoxicity than are routine, nonspecific measures such as cellular protein content and dye-exclusion viability tests, which detect the later stages of cell injury, i.e., cell death.