Captopril inhibited metamphetamine - induced cardiac mitochondrial damage in hyperthermic condition via modulation of biochemical markers

Methamphetamine (METH) is a known abused drug which could induce cardiotoxicity. Captopril is an angiotensin converting enzyme inhibitor that is used in hypertension therapy and has known antioxidant effects. In this study we evaluated the effect of captopril against METH-induced toxicity in rat heart isolated mitochondria in hyperthermic condition.
Mitochondrial fractions were isolated from heart of Wistar rat with different centrifuge technique. Then, heart isolated mitochondrial were exposed to METH (LC50, 250µM) and captopril (0, 25, 50, 100, 200, 400 µM) and incubated at 37 and 41 C. After 1 h incubation, mitochondrial damage was assayed by MTT test. Also, oxidative stress markers were measured.
Our results showed that METH significantly induced mitochondrial damage that was more pronounced in hyperthermic condition. Increased oxidative stress markers such as lipid peroxidation, reactive oxygen species formation and glutathione oxidation in the heart isolated mitochondria were observed after METH exposure that was more significant at 41 c than 37 C. Captopril significantly inhibited METH–induced oxidative stress in the heart isolated mitochondria. Also, captopril pretreatment significantly improved mitochondrial function. Mitochondrial swelling also increased after METH exposure, but was significantly decreased with captopril pre-treatment.
These results suggested that captopril could ameliorate METH-induced oxidative stress and mitochondrial dysfunction especially in hyperthermic condition. Therefore, the effectiveness of this antioxidant should be evaluated for the treatment of METH cardiotoxicity