What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin-induced cardiotoxicity (n=21). Intervention: Enoxaparin vs. Doxorubicin only (2.5 mg/kg i.p. thrice weekly). Primary outcome: Serum cardiac troponin I (cTnI) levels (p=0.017).

January 10, 2018BMC Pharmacology and Toxicology127 citationsOpen Access

Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis

RSReem Ali ShakerMinistry of Health SASamer Hassan AbboudUniversity of Kufa HAHayder AssadUniversity of Kufa

Key Result

Enoxaparin significantly attenuated doxorubicin-induced cardiotoxicity in rats, evidenced by reduced cardiac troponin I levels and improved histopathological scores compared to doxorubicin alone.

Structured PICO

Does enoxaparin reduce doxorubicin-induced cardiotoxicity in a rat model?

Population

21 adult male Wistar albino rats were randomly allocated to evaluate the cardioprotective effects of enoxaparin against doxorubicin-induced cardiotoxicity over a two-week period.

Intervention

Enoxaparin (250 IU/kg/day i.p.) plus doxorubicin (2.5 mg/kg i.p. thrice weekly) for two weeks

Comparator

Doxorubicin only (2.5 mg/kg i.p. thrice weekly) and control (0.9% saline i.p. daily) for two weeks

Outcome

Cardiotoxicity indicated by cardiac troponin I (cTnI) and histological lesionssurrogate

Enoxaparin attenuates doxorubicin-induced cardiotoxicity in rats by suppressing oxidative stress, inflammation, and apoptosis.

Main Result

p-value: p=0.017

Limitations

Animal model (rats) which may not fully translate to human clinical settings
Short treatment duration of only two weeks
Small sample size
Enoxaparin did not completely reverse the cardiotoxic effects to baseline control levels

Abstract

BACKGROUND: Doxorubicin (DOX) is commonly used in the treatment of many types of cancers but its cardiotoxicity is limiting its clinical use. Beyond its anticoagulant action, enoxaparin (ENX), a low molecular weight heparin, has been shown to exert multiple pharmacological actions including antioxidant, anti-inflammatory and antiapoptotic effects. Therefore, the current study aimed to assess if ENX could ameliorate cardiotoxicity induced by DOX. METHODS: Twenty-one adult male Wistar albino rats were randomly allocated into three groups (n = 7 each) of control, receiving 0.9% saline (i.p.), DOX, receiving 2.5 mg/kg of DOX (i.p.) thrice weekly; and DOX + ENX, receiving ENX (250 IU/kg/day i.p.) and a DOX dose equivalent to that of the DOX only group. RESULTS: DOX-induced cardiotoxicity was indicated by marked increases in cardiac troponin I (cTnI) and severe histological lesions, which significantly correlated with cardiotoxicity, oxidative stress, inflammation and apoptosis markers, compared to controls. DOX group also showed elevations in malondialdehyde (MDA), a marker of oxidative stress, and reductions in total antioxidant capacity (TAC). Cardiac inflammatory markers including tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and caspase-3, an apoptotic marker, were also elevated in the DOX group. DOX, however, did not significantly alter brain natriuretic peptide (BNP) levels. ENX significantly attenuated, but not completely reversed, DOX-induced cardiotoxicity through lowering cTnI and improving cardiomyopathy histopathological scores as compared to the DOX group. ENX also decreased MDA, increased TAC of rats' heart to levels relatively comparable to control. Significant reductions in TNF-α, IL-1β and caspase-3 were also observed following ENX treatment relative to the DOX only group. CONCLUSIONS: Collectively, these results describe a cardioprotective effect for ENX against DOX-induced cardiotoxicity which is likely facilitated via suppression of oxidative stress, inflammation and apoptosis.

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