Experimental doxycycline overdose in rats causes cardiomyopathy

Summary All reports of doxycycline‐induced cardiomyopathy to date have been limited to accidental oral poisoning in calves. Therefore, the current study investigated the cardiomyotoxic effect of experimental doxycycline overdose in rats as a toxicity model which could be monitored using histopathological and biochemical assays. A total of 38‐week‐old male Wistar rats were divided into three groups consisting of 10 each. The first group was an untreated control group (D0), and the second group (D5) received doxycycline hyclate 25 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 5‐fold higher than the standard dose. The third group (D10) received 50 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 10‐fold higher than the standard dose. The dose continued for 10 consecutive days and revealed that the doxycycline toxicity was dose dependent. Mortality was recorded in the D10 group only (30%). The D5 rats exhibited minimal skeletal muscle injury and slight but significant increases in the skeletal muscle damage indicators creatine kinase (CK) and aspartate aminotransferase (AST) compared to controls. The cardiac muscle of the D5 rats was histologically normal, and the D5 rats also exhibited normal levels of troponin I (cTnI), an indicator of cardiac muscle damage. In contrast, the D10 rats displayed cardiomyopathy, as well as significant increases in the muscle enzymes alanine aminotransferase (ALT), AST and CK and the cardiac damage indicator cTnI compared to control and D5 groups. Pulmonary lesions were observed in the D10 rats, primarily cardiac lesion‐related alveolar heart failure cells. Thus the present study is the first to demonstrate that oral doxycycline poisoning (10 times the therapeutic dose)‐induced cardiomyopathy is not limited to calves and could occur without any predisposing factors.