Protective Effect of α-Lipoic Acid Against Arsenic Trioxide–Induced Acute Cardiac Toxicity in Rats

• Published in: Journal of Pharmacological Sciences 2011, Vol.115(2), pp.244-248
• Main Authors: Kumazaki, Masafumi, Ando, Hitoshi, Sasaki, Akira, Koshimizu, Taka-aki, Ushijima, Kentarou, Hosohata, Keiko, Oshima, Yasuo, Fujimura, Akio
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Antioxidants - pharmacology; Antioxidants - toxicity; Arsenic Trioxide; Arsenicals; cardiac toxicity; Creatinine - blood; Death, Sudden, Cardiac - etiology; Death, Sudden, Cardiac - prevention & control; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - urine; Dose-Response Relationship, Drug; Electrocardiography - drug effects; Heart - drug effects; Oxidative Stress - drug effects; Oxides - toxicity; Protective Agents - pharmacology; Protective Agents - toxicity; Rats; Rats, Wistar; Thioctic Acid - pharmacology; Time Factors; Transaminases - blood; α-lipoic acid
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.10280SC

The clinical use of arsenic trioxide (ATO) is often limited because of its adverse effects. We examined whether α-lipoic acid (LA) protects against the ATO-induced cardiac toxicity. In the chronic study, two of four rats suddenly died by the repeated dosing of ATO, whereas no deaths were observed in combination with LA. In the acute study, continuous ECG recording revealed that intravenous injection of ATO caused transient ST-T change, whereas pretreatment with LA abolished the ATO-induced ECG abnormality in all animals. These results suggest that LA protects against the ATO-induced acute cardiac toxicity and subsequent sudden death in rats.