Adenosine Triphosphate Exerts Cardioprotective Effect on High-Dose Atorvastatin-Induced Heart Damage in Rats

Abstract

Atorvastatin is a statin derivated hypolipidemic drug used in the treatment of hyperlipidemia. High-dose atorvastatin has been shown to significantly reduce adenosine triphosphate (ATP) levels in the heart tissue. Reduction of ATP by atorvastatin causes increased production of reactive oxygen species (ROS), decreased antioxidants, subsequent cell membrane and mitochondrial damage. The present study aimed to biochemically investigate the protective effect of ATP against possible cardiac damage caused by high dose atorvastatin in rats. Male Wistar rats were divided into atorvastatin (ATR), atorvastatin+ATP (AAT) and healthy control (HG) groups. ATP at a 25 mg/kg dose was injected intraperitoneally (ip) to the AAT (n-6) group. 0.9% NaCl as solvent was applied to the ATR (n-6) and HG (n-6) groups by the same route. Afterward, atorvastatin was administered orally at a dose of 20 mg/kg to the AAT and ATR groups. This procedure was repeated once daily for four weeks. At the end of this period, blood samples were taken into tubes to analyze troponin-I (TP-I) by cardiac puncture before animals were sacrificed with high-dose anesthesia. In addition, heart tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), total oxidant (TOS) and total antioxidant (TAS) levels were measured. Biochemical test results showed that in the heart tissues of the ATR group, the oxidative parameters MDA and TOS significantly increased, while the antioxidant parameters tGSH and TAS significantly decreased compared to AAT and HG. Atorvastatin alone administration significantly increased blood TP-I levels, a marker of cardiac tissue damage. However, ATP administration to AAT group animals brought oxidative parameter levels closer to HG, despite high-dose atorvastatin treatment. In addition, the significant decrease in antioxidant levels was prevented by ATP application. High doses of atorvastatin can cause heart damage. ATP treatment was able to prevent atorvastatin-induced oxidative heart damage.