Aluminum uptake and toxicity in cultured mouse hepatocytes

Hepatic aluminum (Al) accumulation in association with hepatobiliary dysfunction has been described in children receiving contaminated parenteral alimentation solutions and in aluminum-overloaded experimental animals. The mechanisms of hepatic Al uptake are not clearly understood, and it is not known whether Al is directly toxic to the hepatic cell or if toxicity occurs from the effect of Al on hepatic iron (Fe) metabolism. Al causes a microcytic hypochromic anemia and concomitant hepatic Al and Fe can accumulate in dialysis patients, suggesting that Al may alter Fe metabolism. Therefore, Al uptake and toxicity were studied in mouse hepatocytes in culture. Al accumulation, cell growth, media hepatic enzyme concentrations, and cell malonyldialdehyde concentrations, a marker of membrane lipid peroxidation, were measured in mouse hepatocytes grown in media containing either Al citrate, transferrin-Al (Tf-Al), or no additions over 96 h. Al uptake occurred only in cells grown in Tf-Al and Al citrate at 24 h and increased linearly achieving cellular concentrations at 96 h of 522 +/- 36 and 186 +/- 12 micrograms/L, respectively, compared with 31 +/- 3 micrograms/L (P less than 0.001) in control media. Inhibition of cell growth occurred at 48, 72, and 96 h (P less than 0.001), and media lactate dehydrogenase and aspartate aminotransferase concentrations increased starting at 48 and 72 h, respectively (P less than 0.001), only in media containing Tf-Al. Cell malonyldialdehyde levels were significantly higher in Tf-Al-loaded mouse hepatocytes compared with control cells at 96 h (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)