Abstract
We have studied the hepatotoxic effects of cocaine and opioids (morphine, heroin, meperidine, methadone and buprenorphine) on two experimental cellular systems: primary monolayer cultures of rat hepatocytes and hepatoma cell lines (FaO and Hep G2). Three methods were used to evaluate cytotoxicity: intracellular measurement of LDH activity, measurement of total attached cellular protein content, and the MTT test. The results show that:
1) Morphine, heroin and cocaine were more toxic to 1-24-hour primary cultures (IC50: 0.16-0.56mM) than to the other liver-derived cells (IC50: 0.62-8.00mM).
2) Meperidine and methadone produced more evident toxic effects on the hepatoma cell lines (IC50: 0.6–2.0 and 0.08–0.25mM, respectively) than on the primary hepatocyte cultures (IC50: 1.7–4.5 and 0.25–0.50mM, respectively).
3) The toxicity of buprenorphine was similar in all cellular systems (IC50: 0.03–0.13mM).
4) With regard to their toxic potential, we found that buprenorphine and methadone were the most toxic compounds in the majority of the tests. On the other hand, meperidine was least toxic to primary hepatocyte cultures, but showed higher toxicity than morphine, heroin and cocaine to the hepatoma cell lines.
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