Antioxidant Agent Nimesulid and β-Blocker Metoprolol Do Not Exert Protective Effects against Rat Mitochondrial DNA Alterations in Adriamycin-Induced Cardiotoxicity

Kotsinas, Athanassios; Gorgoulis, Vassilis G.; Zacharatos, Panayotis; Zioris, Harilaos; Triposkiadis, Filippos; Donta, Ismini; Kyriakidis, Michael; Karayannacos, Panayotis E.; Kittas, Christos

doi:10.1006/bbrc.1998.0124

Cited by 18 publications

(18 citation statements)

References 26 publications

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“…This increase in cardiac enzyme could be due to an increase in their release following DOX treatment. Data presented here is consistent with those previously reported [9][10][11][12][13]. Interestingly, administration of AG to DOX-treated mice resulted in approximately complete reversal of the DOX-induced increase in serum CK.…”

Section: Discussionsupporting

confidence: 93%

“…Efforts have been focused on using antioxidants to protect the heart against DOX toxicity. However, the results were not encouraging since most of these agents only decrease or delay the development of cardiomyopathy and do not provide complete protection [10,12,13,15,16].…”

Section: Introductionmentioning

confidence: 96%

“…The most and the recent evidences, however, strongly suggest that cellular damage induced by DOX is mediated via the formation of free radicals, which are able to initiate lipid peroxidation [9][10][11][12][13]. Tissue with less developed antioxidant defense mechanism such as the heart are highly susceptible to injury by DOXinduced free radicals [14].…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of arabic gum against cardiotoxicity induced by doxorubicin in mice: A possible mechanism of protection

Abd-Allah

Al-Majed

Mostafa

et al. 2002

J Biochem & Molecular Tox

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Arabic gum (AG) is a naturally occurring compound that has been proposed to possess potent antioxidant activity. In this study, the possible effects whereby AG could protect against cardiotoxicity induced by doxorubicin (DOX) in mice were carried out. Administration of single dose of DOX (15 mg/kg, i.p.) induced cardiotoxicity 72 h, manifested biochemically by a significant elevation of serum creatine kinase (CK) (EC 2.7.3.2). In addition, cardiotoxicity was further confirmed by the significant increase in lipid peroxides measured as malondialdehyde (MDA). Administration of AG (25 g/kg) orally for 5 days before and 72 h after DOX injection produced a significant protection against cardiotoxicity induced by DOX. This was evidenced by significant reductions in serum CK and cardiac lipid peroxides. The effect of AG was examined on the superoxide anion radical generated by enzymatic and nonenzymatic methods. The results indicate that AG is a potent superoxide scavenger. The superoxide scavenging effect of AG may explain, at least in part, the protective effect of AG against cardiotoxicity induced by DOX.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Protective effect of arabic gum against cardiotoxicity induced by doxorubicin in mice: A possible mechanism of protection

Abd-Allah

Al-Majed

Mostafa

et al. 2002

J Biochem & Molecular Tox

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“…Several compounds with antioxidant properties, e.g., Trolox, and 5-aminosalicylic acid (5-ASA), have been investigated in vitro and in vivo with some degree of success (DeAtley et al, 1999;Van Vleet et al, 1980). Molecules with in vitro antioxidant effect such as selenium (Van Vleet et al, 1980) or nimesulid (Kotsinas et al, 1999) could not reduce the Dox cardiotoxicity in vivo. Dexrazoxane, an iron chelator with potent antioxidant properties, is the only United States Food and Drug Administration (USFDA) approved drug used for preventing Dox-induced cardiotoxicity.…”

Section: +mentioning

confidence: 99%

Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats

Kwatra

Kumar

Jangra

et al. 2015

Pharmaceutical Biology

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Context: Doxorubicin (Dox) is one of the most active chemotherapeutic agents used to treat various types of cancers. Its clinical utility is compromised due to fatal cardiac toxicity characterized by an irreversible cardiomyopathy. Objective: This study evaluates the cardioprotective potential of naringin (NR) against Dox-induced acute cardiac toxicity in rats. Materials and methods: Male Wistar rats were randomly divided into five groups. NR (50 and 100 mg/kg) was administered intraperitoneally (i.p.) daily from 0 to 14 d. Doxorubicin (15 mg/kg, i.p.) was given as a single dose on the 10th day. On the 14th day, all animals were sacrificed and oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) activities, and all mitochondrial complexes (I-IV) activities were evaluated along with histopathological studies of the heart. Results: Doxorubicin-induced cardiotoxicity was confirmed by increased (p50.05) MDA, decreased (p50.05) GSH levels, SOD, and CAT activities, mitochondrial complexes (I-IV) activities in the heart tissue. NR (100 mg/kg) showed cardioprotection as evident from significant decreased MDA (p50.001) level, raised (p50.001) GSH level, SOD and CAT activities and increased mitochondrial complexes I (p50.01), II (p50.001), III (p50.001), and IV (p50.05) activities. Further, Dox-induced cardiotoxicity was confirmed by histopathological studies. These obtained results indicated the protective role of NR against Dox-induced cardiac toxicity in rats. Conclusion: NR can be used in combination with Dox due to its high cardioprotective effect against Dox-induced cardiomyopathy.

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“…4 It is now clear that COX-2 is an inducible immediate early gene, 11 involved not only in inflammation and cell proliferation 11 but also in differentiation, 12 apoptosis, 13 metastasis, 14 immunologic surveillance 15 and angiogenesis. 16 Nimesulide, a preferential COX-2 inhibitor of nonsteroidal antiinflammatory drugs (NSAIDs), 17 inhibits chemically induced colon, 18,19 mammary, 20 tongue 21 and urinary bladder 22 carcinogenesis in rats. However, it is still important to examine the modifying effects of nimesulide on pancreatic carcinogenesis because the postinitiation and promotion stages are supposed to be organspecific.…”

mentioning

confidence: 99%

A cyclooxygenase‐2 inhibitor, nimesulide, inhibits postinitiation phase of N‐nitrosobis(2‐oxopropyl)amine‐induced pancreatic carcinogenesis in hamsters

Furukawa

Nishikawa

Lee

et al. 2003

Intl Journal of Cancer

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The modification effects of nimesulide, a cyclooxygenase (COX)-2 inhibitor, administration during the postinitiation phase of pancreatic carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Male Syrian hamsters were given 4 weekly s.c. injections of BOP at a dose of 10 mg/kg and thereafter administered 0, 100 or 400 ppm nimesulide in the diet for 36 weeks. Additional groups of hamsters were fed 400 ppm nimesulide without prior BOP initiation or nontreated. At week 40, all surviving animals were killed and development of neoplastic and preneoplastic lesions was assessed histopathologically. The incidence of pancreatic adenocarcinomas was significantly (p < 0.05) decreased in the BOP/400 ppm nimesulide group compared to the BOP alone group. The multiplicity of total lesions of pancreatic adenocarcinoma plus atypical hyperplasia was also significantly (p < 0.05) lowered. Immunohistochemically, COX-2 was clearly expressed in pancreatic and lung tumor cells, whereas expression was not remarkably affected by the 400 ppm nimesulide treatment. Proliferating cell nuclear antigen labeling indices of pancreatic ducts were significantly (p < 0.01) reduced by nimesulide. The incidence and multiplicity of neoplastic lesions in other organs did not significantly differ among the BOP-treated groups, though only the multiplicity of lung tumors showed a tendency to decrease. No neoplastic lesions were detected in animals receiving nimesulide alone. Our results clearly indicate that nimesulide protects against BOP-induced pancreatic tumors in hamsters.

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Antioxidant Agent Nimesulid and β-Blocker Metoprolol Do Not Exert Protective Effects against Rat Mitochondrial DNA Alterations in Adriamycin-Induced Cardiotoxicity

Cited by 18 publications

References 26 publications

Protective effect of arabic gum against cardiotoxicity induced by doxorubicin in mice: A possible mechanism of protection

Protective effect of arabic gum against cardiotoxicity induced by doxorubicin in mice: A possible mechanism of protection

Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats

A cyclooxygenase‐2 inhibitor, nimesulide, inhibits postinitiation phase of N‐nitrosobis(2‐oxopropyl)amine‐induced pancreatic carcinogenesis in hamsters

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