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Hepatic and renal effects of prolonged exposure of rats to 50 p.p.m. methoxyflurane
Abstract:
Male Fischer 344 rats were exposed to air or to 50 p.p.m. methoxyflurane vapour for a period of 14 weeks. At the end of this period, half of the rats in each group were killed; the remainder breathed air only for a further four weeks (recovery period) before being killed. During the exposure period, growth of the methoxyflurane-exposed rats was markedly depressed, though food consumption was similar in the two groups. Both water consumption and urine volume were increased by methoxyflurane, possibly due to the nephrotoxic effect of fluoride, the concentration of which exceeded 50 micromolar in the sera of all exposed rats. At the end of the exposure period, livers of all exposed rats, but no controls, showed focal hepatocellular degeneration and necrosis, and evidence of liver cell regeneration. Fatty change was prominent. During the recovery period, water consumption and urine volumes returned to near-normal levels. At the end of the recovery period, focal necrosis was still observed in the livers, although fatty change was no longer present. No histological abnormalities were observed in the kidneys of any rats.
Insights
Methoxyflurane exposure in rats caused significant growth depression and liver damage, including hepatocellular degeneration and necrosis. While some liver and kidney functions normalized after recovery, histological liver abnormalities persisted, indicating potential long-term effects.
Area of Science:
- Toxicology
- Hepatology
- Nephrology
Background:
- Methoxyflurane is an anesthetic agent with known toxic potential.
- Fluoride release from methoxyflurane metabolism can lead to nephrotoxicity.
- Long-term effects of methoxyflurane exposure on liver and kidney function require further investigation.
Purpose of the Study:
- To investigate the effects of chronic methoxyflurane exposure on Fischer 344 rats.
- To evaluate the reversibility of methoxyflurane-induced toxicity during a recovery period.
- To assess the impact on growth, water/urine balance, and liver/kidney histology.
Main Methods:
- Male Fischer 344 rats were exposed to 50 p.p.m. methoxyflurane for 14 weeks.
- A subset of rats underwent a 4-week recovery period breathing only air.
- Body weight, food/water consumption, urine volume, serum fluoride levels, and liver/kidney histology were analyzed.
Main Results:
- Methoxyflurane exposure significantly depressed rat growth and increased water consumption and urine volume.
- Elevated serum fluoride levels (>50 micromolar) were observed in exposed rats.
- Hepatocellular degeneration, necrosis, and fatty changes were prominent in exposed rat livers, with some necrosis persisting post-recovery.
- No histological abnormalities were found in the kidneys.
Conclusions:
- Chronic methoxyflurane exposure induces significant hepatotoxicity and affects growth and water balance in rats.
- While some physiological parameters normalize, liver damage may persist after cessation of exposure.
- The nephrotoxic potential of fluoride released from methoxyflurane warrants consideration.