Abstract
Streptozotocin (STZ) has long been used to induce experimental diabetes mellitus to study diabetic complications such as diabetic cardiomyopathy. However, direct impact of STZ on cardiac function is unknown. This study was designed to evaluate the cardiac contractile effect of STZ in isolated adult rat ventricular myocytes. Contractile properties were assessed with an IonOptix MyoCam system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR 90 ), and maximal velocities of shortening/relengthening (± d L /d t ). Intracellular Ca 2+ handling was evaluated with the fluorescent dye fura-2. Acute exposure of STZ (10 −9 –10 −5 M) depressed PS, prolonged TR 90 , and decreased electrically stimulated intracellular Ca 2+ rise in a concentration-dependent manner. TPS, ± d L /d t , resting intracellular Ca 2+ level, and intracellular Ca 2+ clearing rate were unaffected. The STZ-induced mechanical alterations were alleviated by the antioxidant vitamin C (100 μM) and the p38 MAP kinase inhibitor SB203580 (1 μM). 2 ′ ,7 ′ -Dichlorofluorescein diacetate staining revealed enhanced production of reactive oxygen species following STZ treatment, which was prevented by either vitamin C or SB203580. Collectively, our data provided convincing evidence that the tool drug for experimental diabetes STZ may itself cause deleterious cardiac contractile dysfunction via an oxidative stress and p38 MAP kinase-dependent mechanism. Thus, caution should be taken when assessing diabetic heart complications using STZ-induced diabetic models.
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More From: Biochemical and Biophysical Research Communications
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