Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats

Dragojević-Simić, Viktorija; Dobrić, Silva; Jacević, Vesna; Bokonjić, Dubravko; Milosavljević, Ivica; Kovacevic, Aleksandra; Mikić, Dragan

doi:10.2298/vsp110905041d

Cited by 11 publications

(11 citation statements)

References 23 publications

(30 reference statements)

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“…Injury to these organs has been attributed to oxidative stress induced by the reactive intermediate doxorubicin semiquinone, formed from DXR [14]. Thus, several antioxidants have been tested in studies to alleviate the toxic effects of DXR [14,15]. In this study, we assessed the efficacy of RA, which has anti-inflammatory, antimicrobial and antioxidant effects on DXR-induced testicular damage [7].…”

Section: Discussionmentioning

confidence: 99%

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Protective Effects of Rosmarinic Acid on Doxorubicin-Induced Testicular Damage

Üyetürk

Üyetürk²,

Fırat³

et al. 2014

Chemotherapy

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Background: We investigated the protective effects of rosmarinic acid (RA) on testicular damage induced by doxorubicin (DXR) in rats. Methods: In total, 21 rats were divided into 3 groups: the control group that received no treatment, the DXR group that received intraperitoneal (i.p.) DXR on day 7 and the DXR + RA group that received intragastric RA for 10 days with i.p. DXR on day 7. The rats were sacrificed on day 11 for histological and biochemical analyses. To assess oxidative damage, glutathione peroxidase (GPx) and malondialdehyde (MDA) levels were measured. Results: The median modified Johnsen score of the DXR + RA group was higher than that of the DXR group (p = 0.002). The rats with the narrowest seminiferous tubules were in the DXR group (0.17 ± 0.03), and the difference between the DXR + RA and DXR groups was statistically significant (p = 0.002). The number of apoptotic cells in the DXR group was significantly higher than that in the control group, and there were significantly fewer apoptotic cells in the DXR + RA group than in the DXR group (p = 0.002). The MDA level was lowest in the control group and highest in the DXR group, and the level observed in the DXR + RA group significantly lower than that in the DXR group (p = 0.002). The GPx level was highest in the control group, with the level observed in the DXR + RA group significantly higher than that in the DXR group (p = 0.002). The testosterone level was lowest in the DXR group and highest in the control group, and that observed in the DXR + RA group was significantly higher than that in the DXR group (p = 0.018). Conclusions: RA can correct DXR-induced testicular damage through its antioxidant properties. However, the mechanism underlying the effects of RA requires further investigation, and long-term and comparative human studies are also needed.

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Section: Discussionmentioning

confidence: 99%

“…For example, Dragojevic-Simic et al [15 ]explored the efficacy of amifostine, a broad-spectrum cytoprotector, on the cardiotoxic effects of DXR and showed that it had a cardioprotective effect in DXR-induced injury. Shivakumar et al [14 ]assessed the impact of vitamin E on tissue damage caused by DXR in the heart, kidney, liver and testes.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Rosmarinic Acid on Doxorubicin-Induced Testicular Damage

Üyetürk

Üyetürk²,

Fırat³

et al. 2014

Chemotherapy

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“…There are numerous experimental models concerning these subjects, which showed DOX-induced bone marrow toxicity, cardiotoxicity, hepatotoxicity, nephrotoxicity, and toxic effects on the GI tract (GIT), reproductive system, and nervous system [4,9,10,11,12,13,14,15]. DOX acts as a strong inhibitor of DNA duplication and transcription, with the most obvious consequences on tissues with strong proliferative potential, such as bone marrow, GIT, and the reproductive system.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, DOX, by virtue of its quinone group, generates free radicals in vitro and in vivo, which is significantly stimulated by its interaction with iron. Moreover, oxidative stress, apoptosis, and inflammation can be taken as possible mechanisms of DOX multiple-organ toxicity, such as cardiotoxicity on the first place [5,12,15,16,17,18,19]. …”

Section: Introductionmentioning

confidence: 99%

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The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

Jaćević

Dragojević-Simić

Tatomirovic

et al. 2018

IJMS

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Amifostine is well known cytoprotector which is efficient when administered before a wide range of antineoplastic agents. The aim of our study was to investigate amifostine effects on doxorubicin-induced toxic changes in rats. Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin (cumulatively 20 mg/kg ip, for 28 days). The animals’ whole-body, liver, and kidney weight, serum biochemical examination, as well as microscopic examination of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the study. Hepatic and renal alterations were carefully quantified by semiquantitative grading scales—hepatic and renal damage score, respectively. In amifostine-pretreated rats, the number of peripheral blood leukocytes was significantly higher in comparison to doxorubicin-only treated group, preferentially protecting neutrophils. In the same group of rats, hepatic and renal alterations associated with polymorphonuclear cell infiltrates were significantly less severe than those observed in animals receiving only doxorubicin. Our results showed that amifostine successfully protected rats against multiple-dose doxorubicin-induced toxicity by complex, and still not fully elucidated mechanisms of action.

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Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

Birari

Wagh

Patil

et al. 2020

Cancer Chemother Pharmacol

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Purpose Aloin, an anthraquinone present in the aloe species, possesses antiangiogenic, chemopreventive and antioxidant properties. It exerts cytotoxicity against breast cancer and ovarian cancer cell lines. These properties of aloin project it as a chemopreventive adjuvant to anticancer chemotherapy. Methods We evaluated the effect of concurrent oral administration of aloin against doxorubicin (DOX)-induced cardiotoxicity in rats. The protective effects of aloin against DOX-induced toxicity were evident as a statistically significant inhibition of a rise in the biochemical markers of myocardial damage including lactate dehydrogenase (LDH), creatinine kinasemyocardial band (CK-MB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Results Aloin dose dependently inhibited the DOX-induced changes in ECG like increased ST-height and prolonged QT interval. It protected heart against the lipid peroxidation and restored the levels of antioxidative defenses: reduced glutathione, catalase and superoxide dismutase. Aloin prominently reduced the levels of proinflammatory cytokines-TNF-α, IL-1β and IL-6. Notably, the significant protective effects of aloin were evident even at the strikingly lower doses of 1 and 5 mg/kg per day. Conclusion Our results highlight the necessity to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents.

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Efficacy of amifostine in protection against doxorubicin-induced acute cardiotoxic effects in rats

Abstract: AMI provided a significant protection against DOX-induced acute cardiotoxic effects in rats. This finding implies its potential to be a successful cardioprotector in patients treated with DOX due to malignant diseases.

Cited by 11 publications

References 23 publications

Protective Effects of Rosmarinic Acid on Doxorubicin-Induced Testicular Damage

Protective Effects of Rosmarinic Acid on Doxorubicin-Induced Testicular Damage

The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in Rats

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines

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