Mitochondrial Dysfunction Associated with Doxorubicin

Güven, Cengiz; Sevgiler, Yusuf; Taşkın, Eylem

doi:10.5772/intechopen.80284

Cited by 17 publications

(13 citation statements)

References 88 publications

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“…Hence, the volume of cardiomyocytes consists of 30-40% mitochondria [41]. As mentioned earlier, ROS production in the mitochondria is assumed to be the cause of mitochondria injury [42][43][44]. Doxorubicin has a strong binding affinity to cardiolipin in the inner membrane of mitochondria, that may directly cause the disturbance of the electron transport chain (ETC), which cause increased the ROS dan RNS [45][46][47].…”

Section: Mitochondria Injurymentioning

confidence: 99%

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

et al. 2022

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Doxorubicin is a widely used and promising anticancer drug; however, a severe dose-dependent cardiotoxicity hampers its therapeutic value. Doxorubicin may cause acute and chronic issues, depending on the duration of toxicity. In clinical practice, the accumulative toxic dose is up to 400 mg/m2 and increasing the dose will increase the probability of cardiac toxicity. Several molecular mechanisms underlying the pathogenesis of doxorubicin cardiotoxicity have been proposed, including oxidative stress, topoisomerase beta II inhibition, mitochondrial dysfunction, Ca2+ homeostasis dysregulation, intracellular iron accumulation, ensuing cell death (apoptosis and necrosis), autophagy, and myofibrillar disarray and loss. Natural products including flavonoids have been widely studied both in cell, animal, and human models which proves that flavonoids alleviate cardiac toxicity caused by doxorubicin. This review comprehensively summarizes cardioprotective activity flavonoids including quercetin, luteolin, rutin, apigenin, naringenin, and hesperidin against doxorubicin, both in in vitro and in vivo models.

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Section: Mitochondria Injurymentioning

confidence: 99%

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

et al. 2022

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“…A crucial role of mitochondria to maintain accurate spermatogenesis involves the regulation of mitochondrial dynamics, which are defined by a balance of fission and fusion. Alteration of this balance causes changes in mitochondrial function, which is involved in the pathogenesis of some diseases (Marques‐Aleixo et al., 2018; Guven et al, 2018). It has been documented that enhances in the levels of ROS result in changes in the activity of the proteins involved in the mitochondrial dynamics (Cid‐Castro et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

The antioxidant and anti‐apoptotic potential of Pleurotus eryngii extract and its chitosan‐loaded nanoparticles against doxorubicin‐induced testicular toxicity in male rats

Güzel

Tektemur

et al. 2021

Andrologia

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This study was conducted to evaluate the protective role of Pleurotus eryngii extract (PE) and Pleurotus eryngii extract‐loaded chitosan nanoparticles (PE‐CSNP) against doxorubicin (DOX)‐induced testicular toxicity in rats. Male rats were divided into six groups: control (DMSO/ethanol), PE (200 mg/kg PE), PE‐CSNP (30 mg/kg PE‐CSNP), DOX (10 mg/kg DOX, a single dose, i.p), DOX+PE (10 mg/kg DOX+200 mg/kg PE) and DOX+PE‐CSNP (10 mg/kg DOX+30 mg/kg PE‐CSNP). PE and PE‐CSNP were administered by oral gavage every other day for 21 days. DOX‐treated rats showed histopathological impairment compared with the control group. There was an increase in the apoptotic index, caspase 3 (CASP3), BCL2‐associated X apoptosis regulator (BAX), dynamin‐related protein 1 (DRP1) expression and total oxidative status (TOS) in the DOX group, while mitofusin‐2 (MFN2), total antioxidative status (TAS) and serum testosterone levels of the DOX group reduced when compared with the other groups. PE and PE‐CSNP treatments provided significant protection against DOX‐induced oxidative stress by reducing TOS levels and increasing TAS levels. CASP3, BAX, apoptotic index and DRP1‐MFN2 expressions were restored by PE and PE‐CSNP. However, the PE‐CSNP showed higher antioxidant and anti‐apoptotic efficacy compared with PE. Thus, our results provide evidence that CSNP and PE could synergistically have a potent antioxidant and anti‐apoptotic therapy against DOX‐induced testicular damage in male rats.

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“…DxR is a standard-of-care nonselective anthracycline molecule routinely used in the treatment of leukemia [ 21 ]. In this study, we demonstrated that Jurkat leukemia cells, if they are to survive a DxR assault, must quickly change mitochondrial morphology, rates of oxidative phosphorylation, and respiratory capacity.…”

Section: Discussionmentioning

confidence: 99%

Mitofusin-2 mediates doxorubicin sensitivity and acute resistance in Jurkat leukemia cells

Decker

Garcia

Gatchalian

et al. 2020

Biochemistry and Biophysics Reports

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Mitochondria oscillate along a morphological continuum from fragmented individual units to hyperfused tubular networks. Their position at the junction of catabolic and anabolic metabolism couples this morphological plasticity, called mitochondrial dynamics, to larger cellular metabolic programs, which in turn implicate mitochondria in a number of disease states. In many cancers, fragmented mitochondria engage the cell with the biosynthetic capacity of aerobic glycolysis in service of proliferation and progression. Chemo-resistant cancers, however, favor remodeling dynamics that yield fused mitochondrial assemblies utilizing oxidative phosphorylation (OXPHOS) through the electron transport chain (ETC). In this study, expression of Mitofusin-2 (MFN-2), a GTPase protein mediator of mitochondrial fusion, was found to closely correlate to Jurkat leukemia cell survival post doxorubicin (DxR) assault. Moreover, this was accompanied by dramatically increased expression of OXPHOS respiratory complexes and ATP Synthase, as well as a commensurate escalation of state III respiration and respiratory control ratio (RCR). Importantly, CRISPR knockout of MFN-2 resulted in a considerable decrease of doxorubicin (DxR) median lethal dose compared to a treated wildtype control, suggesting an important role of mitochondrial fusion in chemotherapy sensitivity and acute resistance.

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Mitochondrial Dysfunction Associated with Doxorubicin

Cited by 17 publications

References 88 publications

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

The antioxidant and anti‐apoptotic potential of Pleurotus eryngii extract and its chitosan‐loaded nanoparticles against doxorubicin‐induced testicular toxicity in male rats

Mitofusin-2 mediates doxorubicin sensitivity and acute resistance in Jurkat leukemia cells

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