Experimental doxycycline overdose in rats causes cardiomyopathy

Area of Science:

• Veterinary Medicine
• Toxicology
• Cardiology

Background:

• Doxycycline-induced cardiomyopathy reports were previously limited to accidental oral poisoning in calves.
• A need existed to establish a reliable animal model for studying doxycycline cardiotoxicity.

Purpose of the Study:

• To investigate the cardiomyotoxic effects of experimental doxycycline overdose in rats.
• To establish a rat model for monitoring doxycycline-induced cardiomyopathy using histopathological and biochemical assays.

Main Methods:

• Male Wistar rats (n=30) were divided into three groups: control (D0), doxycycline 25 mg/kg twice daily (D5), and doxycycline 50 mg/kg twice daily (D10) for 10 days.
• Histopathological examination and biochemical assays (CK, AST, ALT, cTnI) were used to assess toxicity.
• Mortality and clinical signs were monitored.

Main Results:

• Doxycycline toxicity was dose-dependent, with 30% mortality in the D10 group.
• D5 rats showed minimal skeletal muscle injury and slight increases in CK and AST, with normal cardiac histology and troponin I (cTnI).
• D10 rats developed cardiomyopathy, significant increases in ALT, AST, CK, and cTnI, and pulmonary lesions indicative of heart failure.

Conclusions:

• Oral doxycycline poisoning at 10 times the therapeutic dose induces cardiomyopathy in rats.
• This study demonstrates that doxycycline-induced cardiomyopathy can occur in mammals without predisposing factors.
• The rat model effectively demonstrates dose-dependent doxycycline cardiotoxicity and associated pathologies.