Mechanism of the Cardioprotective Effects of Docetaxel Pre-administration Against Adriamycin-Induced Cardiotoxicity

Tomonari, Mari; To, Hideto; Nishida, Motohiro; Mishima, Takashi; Sasaki, Hidetada; Kurose, Hitoshi

doi:10.1254/jphs.10279fp

Cited by 8 publications

(4 citation statements)

References 33 publications

(26 reference statements)

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“…In the present study, DOX intoxication signifi cantly decreased the duration of both QRS complex and P wave, increased the RR interval, QT interval and brought about ST segment elevation. In line with the present study, previous studies demonstrated that the duration of P wave (16) and QRS complex (1,16) decreased, while the RR interval duration (1,17,18,(19)(20) increased. P wave, QRS complex duration, and RR interval are frequently transient and no specifi city to DOX-induced toxicity can be assigned to them.…”

Section: Discussionsupporting

confidence: 93%

“…P wave, QRS complex duration, and RR interval are frequently transient and no specifi city to DOX-induced toxicity can be assigned to them. Many studies are in agreement with our study by reporting that QT interval prolongation and ST segment elevation brought about by DOX administration have been relatively characteristic ECG fi ndings as a result of DOX-induced cardiotoxicity (1,16,17,18,19,(20)(21). The prolongation of QT interval and ST segment elevation may be linked to the cellular membrane damage owing to oxidative stress (22,23).…”

Section: Discussionsupporting

confidence: 90%

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Cardioprotective effect of melatonin and agomelatine on doxorubicin-induced cardiotoxicity in a rat model: an electrocardiographic, scintigraphic and biochemical study

Aygün¹,

Gül²

2019

BLL

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AIM: The present study aimed to determine the protective effect of melatonin and agomelatine on DOX-induced cardiotoxicity in rats by electrocardiographic, scintigraphic and biochemical methods. MATERIALS AND METHODS: Forty-nine male Wistar rats were randomly separated into seven groups; control (CON), doxorubicin (DOX), melatonin (MEL), agomelatine (AGO), melatonin+doxorubicin (MEL+DOX), agomelatine+doxorubicin (AGO+DOX) and melatonin+agomelatine+doxorubicin (MEL+AGO+DOX) groups. Cardiotoxicity was induced by intraperitoneal (i.p.) injection of DOX (18 mg/kg daily for three days). Rats receiving MEL and AGO treatment in the DOX-induced cardiotoxicity group received MEL and AGO (40 mg/kg/day, i.p., for seven days). They were injected with doxorubicin (18 mg/kg, i.p.) on days 5, 6, and 7. The rats were given MEL and AGO as substance control (40 mg/kg/day, i.p., for 7 days). On day 8 of the experiment, animals were evaluated by means of electrocardiography (ECG) and 99m technetium pyrophosphate (99m Tc PYP) scintigraphy and their biochemical parameters [blood urea nitrogen (BUN), creatine kinase (CK), cardiac troponin T (cTnT)] were examined. RESULTS: DOX-induced acute cardiotoxicity in rats is characterized by conduction abnormalities in the ECG pattern (including decreased P wave and QRS complex duration, increased QT and RR intervals, and STsegment elevation), increased serum BUN, CK, and cTnT parameters and increased 99m Tc PYP uptake (p < 0.001). Pretreatment with MEL, AGO, or MEL+AGO effectively alleviated DOX-induced ECG abnormalities close to normal (p < 0.001). Moreover, serum biochemical evidence and 99m Tc PYP uptake values demonstrated that pretreatment with MEL, AGO, or MEL+AGO has the same protective effect against the abnormalities produced in the heart by DOX (p < 0.001). CONCLUSIONS: MEL and AGO have a potential protective effect on DOX-induced cardiotoxicity. At the same time, this study suggests that 99m Tc PYP is a non-invasive method suitable for early determination of DOX-induced cardiotoxicity (Tab. 3, Fig. 5, Ref. 41).

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Cardioprotective effect of melatonin and agomelatine on doxorubicin-induced cardiotoxicity in a rat model: an electrocardiographic, scintigraphic and biochemical study

Aygün¹,

Gül²

2019

BLL

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“…Adriamycin can lead to the production of free radicals and cell oxidative damage in the body. The free radicals directly attack the membrane lipids, causing the changes in membrane structure and function 12 . The large dose of adriamycin can seriously inhibit the myocardial contractile function of rats, leading to the AHF.…”

Section: ■ Discussionmentioning

confidence: 99%

Protective effects of Polygonatum sibiricum polysaccharide on acute heart failure in rats

Zhu

Chen

et al. 2018

Acta Cir. Bras.

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To investigate the protective effects of Polygonatum sibiricum polysaccharide (PSP) on acute heart failure (AHF) in rats. Methods: Sixty rats were randomly divided into control, model, and low-, middle-and highdose PSP groups, 12 rats in each group. The low-, medium-and high-dose PSP groups were intragastrically administrated with 100, 200 and 400 mg/kg PSP for 5 days, respectively. On the sixth day, the AHF model was established by intraperitoneal injection of adriamycin. After 24h, the cardiac function, serum biochemical indexes, myocardial ATPase and succinate dehydrogenase levels and apoptosis related protein expressions were determined. Results: Compared with model group, in high-dose PSP group the heart rate, left ventricular systolic pressure, ±dp/dt max , serum superoxide dismutase level, myocardial Na +-K +-ATPase, Ca 2+-Mg 2+-ATPase and succinate dehydrogenase levels and myocardial Bcl-2 and Caspase-3 protein expression levels were significantly increased (P<0.05), the left ventricular end diastolic pressure, serum cTnI, CK-MB, TNF-α, IL-6, malondialdehyde and nitric oxide levels and myocardial Bax and cleaved Caspase-3 protein expression levels were significantly decreased (P<0.05). Conclusions: Polysaccharide can prevent the acute heart failure induced by adriamycin. The mechanism may be related to its anti-oxidative stress, anti-inflammation and inhibition of cardiac myocyte apoptosis.

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“…Our results revealed that the ST and QT intervals were significantly extended in mice exposed to free DOX in comparison with those in the control group. Several studies have shown a positive association between DOX cardiotoxicity and QT and ST-interval duration [27][28][29]. ST-interval elongation in DOX-injected mice is due to an increase in action potential duration [30].…”

Section: Ast (U/l) Alt (U/l) Ldh (U/l) Ck-mb (U/l)mentioning

confidence: 99%

The Comparison of Biodistribution, Efficacy and Toxicity of Two PEGylated Liposomal Doxorubicin Formulations in Mice Bearing C-26 Colon Carcinoma: a Preclinical Study

et al. 2016

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Mechanism of the Cardioprotective Effects of Docetaxel Pre-administration Against Adriamycin-Induced Cardiotoxicity

Cited by 8 publications

References 33 publications

Cardioprotective effect of melatonin and agomelatine on doxorubicin-induced cardiotoxicity in a rat model: an electrocardiographic, scintigraphic and biochemical study

Cardioprotective effect of melatonin and agomelatine on doxorubicin-induced cardiotoxicity in a rat model: an electrocardiographic, scintigraphic and biochemical study

Protective effects of Polygonatum sibiricum polysaccharide on acute heart failure in rats

The Comparison of Biodistribution, Efficacy and Toxicity of Two PEGylated Liposomal Doxorubicin Formulations in Mice Bearing C-26 Colon Carcinoma: a Preclinical Study

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