Narcotic effects on phenol red disposition in mice

Area of Science:

• Pharmacology
• Nephrology
• Toxicology

Background:

• Opioid analgesics like morphine are widely used.
• Understanding their effects on renal function is crucial for patient safety.
• Phenol red is a common substance used to assess kidney function.

Purpose of the Study:

• To investigate the impact of morphine and related opioids on the renal clearance of phenol red in mice.
• To elucidate the mechanisms underlying opioid-induced changes in renal elimination.

Main Methods:

• Mice were administered varying doses of morphine subcutaneously.
• Phenol red was administered intravenously to assess plasma clearance and urinary elimination.
• Clearance of p-aminohippurate and iothalamate were measured to assess renal blood flow and glomerular filtration.
• Naloxone was used to explore the role of opioid receptors.

Main Results:

• Morphine administration progressively increased plasma phenol red concentrations and reduced its elimination in urine.
• Morphine significantly reduced phenol red plasma clearance, with effects reversed by naloxone.
• Other opioids like hydromorphone and methadone also reduced phenol red renal elimination.
• Reduced renal elimination of phenol red correlated with decreased p-aminohippurate and iothalamate clearance, suggesting reduced renal blood flow and glomerular filtration.

Conclusions:

• Opioids, including morphine, hydromorphone, and methadone, impair renal elimination of phenol red in mice.
• The mechanism appears to involve reduced renal blood flow and glomerular filtration, not altered urine pH or direct transport competition.
• Naloxone's reversal of morphine's effect confirms the involvement of opioid receptors.