Isoproterenol-Induced Permeability Transition Pore-Related Dysfunction of Heart Mitochondria Is Attenuated by Astaxanthin

Abstract

Mitochondria are key organelles of the cell because their main function is the capture of energy-rich substrates from the cytoplasm and oxidative cleavage with the generation of carbon dioxide and water, processes that are coupled with the synthesis of ATP. Mitochondria are subject to oxidative stress through the formation of the mitochondrial permeability transition pore (mPTP). Various antioxidants are used to reduce damage caused by oxidative stress and to improve the protection of the antioxidant system. Astaxanthin (AST) is considered to be a dietary antioxidant, which is able to reduce oxidative stress and enhance the antioxidant defense system. In the present investigation, the effect of AST on the functional state of rat heart mitochondria impaired by isoproterenol (ISO) under mPTP functioning was examined. It was found that AST raised mitochondrial respiration, the Ca2+ retention capacity (CRC), and the rate of TPP+ influx in rat heart mitochondria (RHM) isolated from ISO-injected rats. However, the level of reactive oxygen species (ROS) production increased. In addition, the concentrations of cardiolipin (CL), Mn-SOD2, and the proteins regulating mPTP rose after the injection of ISO in RHM pretreated with AST. Based on the data obtained, we suggest that AST has a protective effect in rat heart mitochondria.

The Identification of Prohibitin in the Rat Heart Mitochondria in Heart Failure

“…Mitochondria were isolated from the whole heart according to the method described in [ 28 ]. The heart was purified from blood vessels, crushed and homogenized.…”

Astaxanthin as a Novel Mitochondrial Regulator: A New Aspect of Carotenoids, beyond Antioxidants

“…Oxidative stress disturbs intracellular Ca 2+ homeostasis, resulting in excessive Ca 2+ efflux from the endoplasmic reticulum and an influx into mitochondria, which subsequently triggers mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, and the release of mitochondrial pro-apoptotic factors [ 81 ]. It has been widely reported that AX prevents the ROS-induced Ca 2+ influx into mitochondria, protects against mitochondrial dysfunction, and inhibits apoptosis [ 82 , 83 , 84 , 85 , 86 , 87 , 88 ]. The role of AX in modulating mitochondrial-mediated activation of apoptosis is beyond the scope of this review.…”

Mitochondrion as a Target of Astaxanthin Therapy in Heart Failure

“…In mitochondria, when mPTP is opened, the level of subunit c decreases [ 54 ]. In RHM isolated from rats treated with AST, the content of subunit c increased, which could contribute to an increase in Ca 2+ capacity and a slowdown in mitochondrial swelling [ 85 ].…”

“…The results obtained by histological analysis suggest that the use of AST significantly reduced both degeneration and post ischemic edema of the muscle fibers of the heart, and the degree of fibrotic myocardial damage after acute heart failure caused by ISO. The data obtained using digital bioimaging of transmural histotopograms of left ventricle of the studied groups allowed us to conclude a significant decrease in the degree of fibrosis of subendocardial lesions of the heart, which indicates a protective effect from the administration of AST [ 85 ].…”