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Acute morphologic changes in orbicularis oculi muscle after doxorubicin injection into the eyelid
L K McLoon1, X X Luo, J Wirtschafter
1Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
Abstract:
This study attempts to gain a better understanding of the primary cause of doxorubicin myotoxicity to aid in the development of a protocol to increase its effectiveness in treating muscle spasm diseases. The time course of acute injury to the orbicularis oculi muscle after injection of doxorubicin into the eyelids of rabbits was examined. The effects of doxorubicin injection were immediate and dramatic. Within 5 minutes, the muscle cells in the eyelids showed signs of myofibrillar dissolution. This process continued for the first 24 hours, with a marked decrease in the total number of myofibers by 1 hour after drug treatment. By 4 days after doxorubicin injection, most of the treated muscle had a more normal morphology, although some ongoing myofibrillar dissolution was present. There was evidence for a limited amount of muscle regeneration. Three levels of injury were seen: a severe, irreversible injury in the majority of the myofibers; a mild, reversible injury in a subset of the fibers; and a group of myofibers apparently uninjured as a result of doxorubicin treatment. Doxorubicin toxicity in skeletal muscle is of rapid onset. Understanding the primary cause and acute changes in doxorubicin myotoxicity may accelerate the development of improved protocols to increase the effectiveness of doxorubicin in treating muscle spasm diseases.
Insights
Doxorubicin causes rapid skeletal muscle injury, leading to myofibrillar dissolution and fiber loss. Understanding these acute changes is key to improving doxorubicin treatments for muscle spasm diseases.
Area of Science:
- Muscle physiology
- Pharmacology
- Toxicology
Background:
- Doxorubicin is an effective chemotherapy agent.
- Doxorubicin can cause myotoxicity, limiting its use.
- Muscle spasms require effective treatment protocols.
Purpose of the Study:
- To understand the primary cause of doxorubicin-induced myotoxicity.
- To examine the time course of acute injury to skeletal muscle after doxorubicin injection.
- To inform the development of protocols to enhance doxorubicin's efficacy in treating muscle spasm diseases.
Main Methods:
- Acute injury to the orbicularis oculi muscle in rabbits was examined after doxorubicin injection.
- The time course of myofibrillar dissolution and myofiber changes was observed.
- Histological analysis was performed to assess muscle morphology and regeneration.
Main Results:
- Doxorubicin injection caused immediate and dramatic effects on eyelid muscle.
- Myofibrillar dissolution began within 5 minutes, with significant myofiber decrease by 1 hour.
- Muscle morphology largely normalized by 4 days, with some ongoing dissolution and limited regeneration observed.
- Three injury levels were identified: severe irreversible, mild reversible, and uninjured myofibers.
Conclusions:
- Doxorubicin myotoxicity in skeletal muscle has a rapid onset.
- Understanding acute doxorubicin-induced muscle injury is crucial.
- This knowledge may accelerate the development of improved therapeutic protocols for muscle spasm diseases.