Protective effect of the nitroxide tempol against the cardiotoxicity of adriamycin

Monti, Elena; Cova, D.; Guido, Emanuela; Morelli, Roberto; Oliva, Cesare

doi:10.1016/0891-5849(96)00124-4

Cited by 98 publications

(53 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Swelling of hepatocytes, causing ALT/AST release, as observed in Nrf2 -/-mice fed iron-rich diet, are typical features of ROS-induced necrosis in vivo [18]. Further evidence of iron-mediated oxidative stress is provided by the increased levels of a specific marker of oxidative DNA damage (8-OHdG) in hepatocytes from Nrf2 -/-mice fed iron-rich diet and the abrogation of the hepatotoxicity of dietary iron via the use of an antioxidant that is targeted to the mitochondria (mito-TEMPOL), which is capable of trapping free radicals and inhibiting the catalytic action of Fe 2+ [30]. A striking feature of necrotic hepatocytes from Nrf2 -/-mice fed iron-rich diet was the extreme swelling of mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

Silva‐Gomes

Santos

Caldas

et al. 2014

Journal of Hepatology

View full text Add to dashboard Cite

Background & Aims:The l i v e r , being the major site of i r o n storage, is particularly exposed to the toxic effects of iron. Tran-scription factor NRF2 is critical for protecting the l i v e r a g a i n s t disease by activating the transcription of genes encoding detoxification/antioxidant enzymes. We aimed to determine if the NRF2 pathway plays a significant role in the protection against hepatic iron overload. Methods: Wild type and Nrf2 _ /_ mouse primary hepatocytes Wereincubated with ferric ammonium citrate. Wild type and Nrf2 -/-mice w e r e fed s t anda rd rodent chow or iron-rich diet for 2 weeks, with or without daily i n j e c t i o n of the a n t i o x i d a n t mito-TEMPOL. Results: In mouse hepatocytes, iron induced the nuclear translo-cation of NRF2 and the expression of cytoprotective genes in an NRF2-dependent manner. Moreover, Nrf2 _ /_ hepatocytes were highly susceptible to i r o n -induced cell d e a t h . Wild-type and Nrf2 _ /_ mice fed iron-rich diet accumulated similar amounts of iron in the liver and were equally able to increase the expression of hepatic hepcidin and ferritin. Nevertheless, in Nrf2-null mice the iron loading resulted in progressive liver injury, ranging from mild confluent necrosis to s e v e r e necroinflammatory lesio ns. Hepatocytic cell death was associated with gross ul t r a s t r u c t u r a l damage to the mitochondria. Notably, liver injury was prevented in iron-fed animals that received mito-TEMPOL. Conclusions: NRF2 protects the m o u s e liver against the t o x i c i t y of dietary iron o v e r l o a d by p r e v e n t i n g hepatocytic cell d e a t h . We identify NRF2 as a potential modifier of liver disease in iron overload pathology and show the beneficial effect of the antiox-idant mito-TEMPOL in a mouse model of dietary iron-induced liver injury. ©2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 INTRODUCTIONIron is a component of several metalloproteins involved in crucial metabolic processes such as oxygen sensing and transport, energy metabolism and DNA synthesis. However, iron in excess is detrimental, as it can catalyze the formation of damaging radical species via Fenton-type reactions [1]. In normal conditions, iron toxicity is prevented by the binding of extracellular iron in the plasma to transferrin and by storage of intracellular iron in a protein with high storage capacity, ferritin [2]. In addition, plasma iron levels are tightly regulated by the action of the peptide hormone hepcidin. Hepcidin, which is mostly secreted in the liver, promotes the degradation of the iron exporter ferroportin expressed on the surface of iron-releasing cells, thus reducing intestinal iron absorption and its mobilization fr...

show abstract

Section: Discussionmentioning

confidence: 99%

Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

Silva‐Gomes

Santos

Caldas

et al. 2014

Journal of Hepatology

View full text Add to dashboard Cite

show abstract

“…With a range of remarkable physical and chemical attributes it is no wonder that nitroxides have been utilised in a variety of fields and applications including magnetic resonance imaging (MRI), electron paramagnetic resonance (EPR) spectroscopy, material and biological antioxidants, cellular metabolism, molecular mobility of proteins and lipids, and membrane structure. [290][291][292][293] The first nitroxide to appear in the literature was Frémy's salt (or potassium nitrosodisulfonate, K 2 [NO(SO 3 ) 2 ] (36) (Figure 15), and was discovered by Edmond Frémy in 1845. 294 Frémy's salt is still widely used as a strong oxidizing agent and as an EPR standard for g-value determination.…”

Section: Nitroxidesmentioning

confidence: 99%

“…Over the past 20 years, other novel applications have been proposed for nitroxide compounds after their antioxidant activity was demonstrated in a number of experimental models. 293,[307][308][309][310][311][312] Nitroxides are known to protect cells against 293,308,315 The ability of nitroxides to participate in all of the above pathways relies on redox transformations between three oxidation states -the nitroxide, hydroxylamine and oxoammonium derivatives. Scheme 3 shows the oxidation states of 4-hydroxy-2,2,6,6-tetramethyl-1-piperidinoxyl (38), one of the most widely studied nitroxides in the literature.…”

Section: Nitroxides In Biological Systemsmentioning

confidence: 99%

Heteroorganic molecules and bacterial biofilms: Controlling biodeterioration of cultural heritage

Alexander¹,

Schiesser²

2016

Arkivoc

View full text Add to dashboard Cite

show abstract

“…Nitroxide TEMPOL potentiates the cytotoxicity of doxorubicin in the culture of tumor cells with multidrug resistance (Gariboldi et al, 2006), and reduces its cardiotoxicity in rats (Monti et al, 1996). Combinations of low doses of nitroxyl TEMPO and doxorubicin or mitoxantrone exhibit additive or synergistic cytotoxicity, depending on the type of the tumor cells (Suy et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Platinum Complexes with Bioactive Nitroxyl Radicals: Synthesis and Antitumor Properties

Sen¹,

Terentiev²,

Коновалова³

2012

Nitroxides - Theory, Experiment and Applications

View full text Add to dashboard Cite

Protective effect of the nitroxide tempol against the cardiotoxicity of adriamycin

Cited by 98 publications

References 30 publications

Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death

Heteroorganic molecules and bacterial biofilms: Controlling biodeterioration of cultural heritage

Platinum Complexes with Bioactive Nitroxyl Radicals: Synthesis and Antitumor Properties

Contact Info

Product

Resources

About