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Opioid effects on hepatic disposition of dyes in mice
Abstract:
Morphine administration acutely reduced plasma clearance of sulfobromophthalein (BSP) in mice and increased hepatic retention of this dye. Increasing morphine doses from 5 to 40 mg/kg s.c. progressively raised plasma and liver BSP levels. Morphine-treated mice, warmed to reverse hypothermia, still had higher plasma and liver BSP levels. The narcotic also raised plasma levels of two dyes which are not conjugated, indocyanine green and dibromosulfophthalein. Naloxone reversed morphine-induced elevation of plasma BSP levels. In bile duct-ligated mice, plasma BSP levels were very high but hepatic BSP levels remained low, both after saline or morphine. Thus, the effects of morphine on BSP disposition differed from those of biliary occlusion. BSP content in bile was reduced by morphine, as dye levels were raised in plasma and hepatic parenchyma. In bile duct-cannulated mice morphine increased BSP levels in plasma and liver whereas reducing the amount of dye eliminated in bile.
Insights
Morphine impairs the body's ability to clear sulfobromophthalein (BSP) dye, leading to higher levels in the blood and liver. This effect, seen in mice, suggests morphine impacts liver function and dye excretion.
Area of Science:
- Pharmacology
- Hepatology
- Toxicology
Background:
- Opioid analgesics like morphine can affect physiological processes.
- Drug metabolism and excretion are crucial for liver function.
- Sulfobromophthalein (BSP) is a model compound used to assess liver function.
Purpose of the Study:
- To investigate the effects of morphine administration on the plasma clearance and hepatic retention of sulfobromophthalein (BSP) in mice.
- To determine if morphine affects the disposition of other dyes and if its effects are reversible.
- To differentiate the impact of morphine on BSP disposition from that of biliary obstruction.
Main Methods:
- Administered varying doses of morphine subcutaneously to mice.
- Measured plasma and hepatic levels of BSP and other dyes (indocyanine green, dibromosulfophthalein).
- Utilized naloxone to assess the reversibility of morphine's effects.
- Compared effects in bile duct-ligated and bile duct-cannulated mice.
Main Results:
- Morphine significantly reduced BSP plasma clearance and increased hepatic retention in a dose-dependent manner.
- Morphine elevated plasma levels of unconjugated dyes, indicating a broader impact on dye transport.
- Naloxone reversed the morphine-induced increase in plasma BSP levels.
- Morphine reduced BSP excretion into bile, distinct from the effects of biliary ligation.
Conclusions:
- Morphine acutely impairs the hepatic uptake and/or biliary excretion of BSP and other dyes in mice.
- The observed effects are mediated through opioid receptors, as indicated by naloxone reversal.
- Morphine's impact on BSP disposition differs significantly from mechanical biliary obstruction.