The effect of methadone and naloxone on cultured rat liver cells

Opioids modify hepatic function in vivo, however, a direct effect of this class of drugs on liver cells has not been demonstrated. The potential effect of opioids on liver parenchymal-type cells, therefore, was studied using cultured albumin-secreting rat hepatoma cells. Liver cells were incubated with methadone or naloxone individually or in combination. Dose-response analysis indicated that concentrations of either or both drugs in excess of 2.5 X 10(-5) M were clearly cytotoxic to cultured hepatoma cells. At a concentration (2.5 X 10(-7) M) at which no adverse effect on hepatoma cell viability or growth rate was observed, naloxone, methadone, or naloxone plus methadone produced a 26, 41, and 63% decrease in trichloroacetic acid-precipitable protein (per 10(6) cells), respectively, when compared to control. The inhibitory effect of naloxone, methadone, or naloxone plus methadone on albumin accumulation in the culture medium was greater than the drug-induced reduction of protein synthesis. These studies demonstrate that opioids have several direct effects on cultured hepatoma cells and, therefore, raise the question of whether clinically significant hepatic dysfunction may be produced by the direct action of opioids on the liver.