Selenium-mediated cardioprotection against adriamycin-induced mitochondrial damage

Abstract

Adriamycin (ADR) causes morphological and functional alterations in mitochondrial structure in the heart. The study's aim was to determine whether there is a protective effect of selenium (Se) on ADR-induced cardiac damage. Rats were divided into four groups: The first group was injected saline intraperitoneally (i.p.) for 21 days; the second group received 4 mg/kg i.p. ADR every alternate day for 8 days; the third group received 50 µg/kg i.p. Se for 21 days; and the fourth received the Se (for 21 days) and ADR (for 8 days) coadministration i.p. Left ventricular functions, electrocardiography parameters, and blood pressures were assessed. Mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, and thioredoxin reductase (TrxR) activity were determined. Total antioxidant (TAS) and oxidant status (TOS) in cytosol, mitochondria of myocytes, and plasma were measured. Left ventricular data demonstrated left ventricular systolic pressure (LVSP) decreased, left ventricular developed pressure (LVDP) decreased, and left ventricular end-diastolic pressure (LVEDP) increased in ADR-treated animals, compared to the control and Se groups. ADR decreased the membrane potential and ATP level in myocyte mitochondria. TrxR activity decreased in the ADR group, compared to the Se group. Cytosolic and mitochondrial TAS decreased and mitochondrial and plasma TOS increased in the ADR group, compared to the control. The coadministration of Se with ADR attenuated left ventricular dysfunction, improved MMP and ATP levels, and prevented oxidative stress by increasing antioxidants (especially TrxR) and decreasing oxidants. We concluded that Se is effective against ADR-induced cardiac damage via the restoration of TAS and TOS, which prevented mitochondrial damage.

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

“…It is still not completely understood how ADR can inhibit mitochondrial electron transport and oxidative phosphorylation. However, some evidences have relevted ADR-mitochondrial dysfunction to depolarized MMP (Dursun et al 2011b;Taskin and Dursun 2012;Zhu et al 2011), decreased ATP production (Dursun et al 2011b;Taskin and Dursun 2012;Xu et al 2010;Zhu et al 2011), and disrupted mitochondrial calcium homeostasis (Wallace 2007). ADR also inhibits the transport of some of the proteins from the cytosol to the mitochondria.…”

“…Mitochondria from fresh rat hearts were isolated as described before (Dursun et al 2011b): The hearts were homogenized in an ice-cold buffer A (250 mM sucrose, 2 mM EGTA, 5 mM Tris HCl) with a homogenizer and centrifuged at 2,000g for 8 min at 4 C. The supernatant (cytosol) was further centrifuged at 12,000g for 10 min at 4 C in a new tube. The pellet of mitochondria was suspended in an ice-cold buffer B (140 mM potas sium, 20 mM Tris HCl).…”

The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

“…2,3 Mitochondria may have been suggested to be a primary target of ADR-induced toxicity at the subcellular level. 6,9,38 The ADR also has the tremendous ability to inhibit oxidative phosphorylation, which may account for the impairment of energy metabolism of the cell inhibition of electron transport complexes, and disruption of calcium homeostasis. 38 Mitochondrial degeneration and dysfunction has been reported on ADRinduced toxicity.…”

“…ADR-generated free radicals induce lipid peroxidation, which in turn, causes diverse oxidative damage on critical cellular components and membrane lipids in the plasma membranes and mitochondria. [5][6][7][8][9] In addition, mitochondrial damage, increased Ca 2+ current along with inhibition of sarcoplasmic reticulum function and decreased activity of Na, K-ATPase, have all been implicated in ADR-induced toxicity. 10 The main target of ADR-induced toxicity in cardiomyocytes is mitochondria which accumulate ADR over time.…”

Recovery of adriamycin induced mitochondrial dysfunction in liver by selenium

“…Recent researches have revealed some potential therapeutic agents, such as Se (Benedetti et al 2012;Dursun and Taskin 2011;Koukay et al 1990;Taskin and Dursun 2012), vitamin E (Koukay et al 1990), NAC (N-acetylcysteine) (Wang et al 2014), a-tocopherol (Chautan et al 1992;Myers et al 1982), quercetin (Chen et al 2013) and L-carnosine (Ozdogan et al 2011) effective in limiting the extent of ADR-induced toxicities, all of which are based on the antioxidant properties of the candidate compound. We have already suggested the selenium to be a possible candidate to eliminate its mitochondrial toxicity in heart and kidney (Taskin and Dursun 2012) tissues.…”