Existence of a distinct concentration window governing daunorubicin-induced mammalian liver mitotoxicity—implication for determining therapeutic window

Paul, Manash K.; Patkari, Minal; Mukhopadhayay, Anup K.

doi:10.1016/j.bcp.2007.06.009

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…For instance, daunorubicin increases the mitochondrial respiration at low concentrations and inhibits it at higher concentrations, thus acting as a mitotoxic drug. 40 Recently, a liposomal daunorubicin targeting mitochondria has been shown to exert high cytotoxicity in MCF7-Adr cells in association with the calcium channel blocker amlodipine, by disrupting the mitochondrial potential, releasing the cytochrome c, and activating the caspases cascade. 41 This finding confirms that the mitochondrial metabolism is critical for the survival of drug-resistant cells and is in keeping with what we observed in HT29-dx, where the TCA cycle, the electron transport across complex I, and the synthesis of ATP were higher than in HT29 cells.…”

Section: ■ Discussionmentioning

confidence: 99%

Mitochondrial-Targeting Nitrooxy-doxorubicin: A New Approach To Overcome Drug Resistance

Riganti¹,

Rolando

Kopecka³

et al. 2012

Mol. Pharmaceutics

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Section: ■ Discussionmentioning

confidence: 99%

Mitochondrial-Targeting Nitrooxy-doxorubicin: A New Approach To Overcome Drug Resistance

Riganti¹,

Rolando

Kopecka³

et al. 2012

Mol. Pharmaceutics

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“…One of the widespread methods in detecting ROS production by mitochondria is based on 2′ 7′- dichloroflourescein (H2DCFDA) oxidation [35] H2DCFDA, an uncharged, cell-permeable fluorescent probe readily diffuses into cells and gets hydrolyzed by intracellular esterases to yield H2DCF, which is trapped inside the cell. Then it is oxidized from the nonfluorescent form to a highly fluorescent compound dichlorofluoresce in by hydrogen peroxide (H 2 O 2 ) or other low-molecular-weight peroxides produced in the cells.…”

Section: Methodsmentioning

confidence: 99%

Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: Possible involvement of mitochondrial dysfunction, inflammation and apoptosis

2016

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The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP) against Cadmium (Cd) induced hepatic inflammation, apoptosis and hepatic mitochondrial toxicity in rats. Male Wistar rats were distributed in four experimental groups: control, GSP, Cd and Cd + GSP. Exposure to a hepatotoxic dose of Cd (5 mg/kg BW) caused liver damage, coupled with enhanced reactive oxygen species (ROS) generation, increased inflammation and apoptosis in liver with increased DNA damage in hepatocytes of rats. Mitochondria were isolated from the hepatic tissues of rats from each group. Our results showed significant decrease in the tri-carboxylic acid cycle enzymes, increased mitochondrial swelling, inhibition of cytochrome c oxidase activity and complex I–III, II–III and IV mediated electron transfer, decreased mitochondrial ATPases, a reduction in calcium content and mitochondrial oxygen consumption in Cd treated rats. All these molecular changes caused by Cd were alleviated by the pre-supplementation with GSP (100 mg/kg BW). The ultra structural changes in the liver also support our findings. From our results, it is clearly indicated that the free radical scavenging, metal chelating and antioxidant potentials of GSP might be the possible reason, responsible for the rescue action against Cd induced mitochondrial damage in the liver of rats.

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“…The mechanism of DNR-induced toxicity is reported to be mainly linked to oxidative stress. , The quinone and hydroquinone groups in DNR are converted to radical species by oxoreductive enzymes. Thereafter, semiquinone generates excess reactive oxygen species (ROS), such as superoxide anion (O 2 •– ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical ( • OH), leading to lipid peroxidation and cell damage . The overproduction of ROS can not only cause cell damage but also amplify inflammation .…”

Section: Introductionmentioning

confidence: 95%

“…•− ), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical ( • OH), leading to lipid peroxidation and cell damage. 12 The overproduction of ROS can not only cause cell damage but also amplify inflammation. 13 Activated Kupffer cells secrete inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), which recruit both neutrophils and macrophages to expand the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation

Bai

Kong

Feng

et al. 2021

ACS Appl. Mater. Interfaces

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Anthracycline-induced liver injury (AILI) is becoming an increasingly serious and potential clinical complication and is linked to reactive oxygen species (ROS) production and subsequent inflammatory response. Herein, we demonstrated that artificial Prussian blue nanozymes (PBZs) prevented daunorubicin-induced liver injury, a prototype of AILI, by attenuating ROS production and regulating inflammation. PBZs exhibited multienzyme activity and could scavenge ROS and free radicals. At the cellular level, PBZs could effectively eliminate ROS, suppress hepatocyte apoptosis, reduce deoxyribonucleic acid damage, and decrease the levels of inflammatory cytokines and chemokines. According to the results of the in vivo study, pretreatment with PBZs also resulted in a desirable protective effect against AILI, as indicated by both a decrease in biochemical indicator levels and hepatocyte necrosis. PBZs upregulated antioxidative genes by activating the Nrf2 pathway to reduce oxidative stress. Meanwhile, PBZs counteracted the inflammatory response based on the decreased expression levels of myeloperoxidase and F4/80 in the liver. Collectively, our findings indicate that PBZ-based nanotherapy is a novel strategy for protecting against AILI.

show abstract

Existence of a distinct concentration window governing daunorubicin-induced mammalian liver mitotoxicity—implication for determining therapeutic window

Cited by 8 publications

References 29 publications

Mitochondrial-Targeting Nitrooxy-doxorubicin: A New Approach To Overcome Drug Resistance

Mitochondrial-Targeting Nitrooxy-doxorubicin: A New Approach To Overcome Drug Resistance

Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: Possible involvement of mitochondrial dysfunction, inflammation and apoptosis

Prussian Blue Nanozymes Prevent Anthracycline-Induced Liver Injury by Attenuating Oxidative Stress and Regulating Inflammation

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