Histopathological studies of microtubule disassembling agent-induced myocardial lesions in rats

Tochinai, Ryota; Ando, Minoru; Suzuki, Tomo; Suzuki, Katsuya; Nagata, Yoshiaki; Hata, Chie; Uchida, Kazumi; Kobayashi, Takuma; Kado, Shoichi; Kaneko, Kimiyuki

doi:10.1016/j.etp.2012.09.008

Cited by 17 publications

(18 citation statements)

References 21 publications

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“…This vasospasm regularly occurred on days 6-8 after the fourth to sixth cycles of the anticancer agent and alterations in endothelium-dependent vasodilation (De Vos, Willemse, De Vries, & Gietema, 2004), and/or ROS-derived endothelial cell damage can be involved (Rittenberg, Gralla, & Rehmeyer, 1995). In our study, the vascular toxicity observed in VIN-treated rats does not translate to changes in blood pressure or heart rate, so it is possible that we are at an early stage of events, leading to VIN-induced cardiovascular toxicity; other authors demonstrated more extensive cardiovascular toxicity of VIN (Panda & Kar, 2015;Tochinai et al, 2013).…”

Section: Discussionmentioning

confidence: 64%

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

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Abalo

et al. 2018

European Journal of Pain

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Background The antineoplastic drugs cisplatin and vincristine induce peripheral neuropathies. The sigma‐1 receptor (σ1R) is expressed in areas of pain control, and its blockade with the novel selective antagonist MR‐309 has shown efficacy in nociceptive and neuropathic pain models. Our goal was to test whether this compound reduces neuropathic signs provoked by these antitumoural drugs. Methods Rats were treated with cisplatin or vincristine to induce neuropathies. The effects of acute or repeated administration of MR‐309 were tested on mechanical and thermal sensitivity, electrophysiological activity of Aδ‐primary afferents in the rat skin–saphenous nerve preparation, and gastrointestinal or cardiovascular functions. Results Rats treated with antitumourals developed tactile allodynia, while those treated with vincristine also developed mechanical hyperalgesia. These in vivo modifications correlated with electrophysiological hyperactivity (increased spontaneous activity and hyperresponsiveness to innocuous and noxious mechanical stimulation). Animals treated with cisplatin showed gastrointestinal impairment and those receiving vincristine showed cardiovascular toxicity. A single dose of MR‐309 strongly reduced both nociceptive behaviour and electrophysiological changes. Moreover, its concomitant administration with the antitumourals blocked the development of neuropathic symptoms, thus restoring mechanical sensitivity, improving the impairment of feeding behaviour and gastrointestinal transit in the cisplatin‐treated group along with ameliorating the altered vascular reactivity recorded in rats treated with vincristine. Conclusion σ1R antagonist, MR‐309, reduces sensorial and electrophysiological neuropathic signs in rats treated with cisplatin or vincristine and, in addition, reduces gastrointestinal and cardiovascular side effects. Significance σ1R antagonism could be an interesting and new option to palliate antitumoural neuropathies.

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Section: Discussionmentioning

confidence: 64%

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

Paniagua

Goicoechea

Abalo

et al. 2018

European Journal of Pain

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“…Fatal radiculomyeloencephalopathy can occur after accidental intrathecal administration [5]. Cardiac toxicity induced by vinca alkaloids has been rarely reported [6,7,8]. Myocardial infarcts have been described, occurring from several hours to 3 days after the administration of vincristine.…”

Section: Discussionmentioning

confidence: 99%

Coronary Spasm after an Injection of Vincristine

et al. 2017

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Cardiotoxicity, including heart failure, thromboembolic events, and myocardial ischemia, is a concern for cardiologists and oncologists. The most frequently involved drugs are anthracyclines. We report an episode of coronary spasm due to vincristine, a vinca alkaloid, in a 49-year-old man treated for a diffuse undifferentiated carcinoma. The patient suffered recurrent episodes of typical chest pain with ST-elevation in the inferior area. Coronary spasm was confirmed by an angiogram, which showed normal coronary arteries. No recurrence occurred with the medical management. Coronary spasm induced by vincristine is a newly described facet of chemotherapy-related cardiotoxicity.

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“…Moreover, it has been suggested that colchicine may have a toxic effect on cardiac impulse generation and conduction in humans 10 . Experimental studies have demonstrated that colchicine induces impairment of the intrinsic contractility of the myocardium 15 and histopathologic changes in the heart 16 , 17 .…”

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confidence: 99%

“…During the period of ECG recording, 1.25 mg/kg colchicine (Wako Pure Chemical Industries, Osaka, Japan) dissolved in 5% glucose at a volume of 1 mL/kg was administered intravenously into the rats once daily for 2 consecutive days. This dosing schedule for colchicine is known to induce histopathological changes in the rat heart based on our previous study 17 . The ECG-wave components (RR interval, QRS duration, PR interval and QT interval) were analyzed in 10 consecutive beats, and power spectral analysis of heart rate variability was performed at 23, 21, 18 and 12 hours before the first injection; 1, 3, 6, 12 and 23 hours after the first injection; and 1, 3, 6 and 12 hours after the second injection.…”

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confidence: 99%

“…After collection of whole blood, the heart, gastrocnemius muscle, liver, kidneys and stomach were extracted and immediately fixed in 10% neutral phosphate-buffered formalin. Also, hearts were cross-sectioned at one point in atria with the atrioventricular node and two points in ventricles as described in our previous report 17 . Fixed organs were embedded in paraffin and sectioned at a thickness of 4–6 μm.…”

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Cardiotoxic Changes of Colchicine Intoxication in Rats: Electrocardiographic, Histopathological and Blood Chemical Analysis

et al. 2014

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The microtubule inhibitor colchicine is cardiotoxic and is suggested to impair impulse formation and conduction. However, little is known about the electrocardiographic (ECG) changes induced by colchicine in experimental animals and the detailed pathogenesis of its cardiotoxicity. Therefore, we analyzed cardiotoxicity in colchicine-treated rats using electrocardiographic, histopathological and blood-chemistry approaches. A telemetry device for transmitting ECG data was implanted into male Crl:CD(SD) rats, and ECG tracings were obtained. At 6 weeks of age, 1.25 mg/kg colchicine was injected intravenously once daily for 2 consecutive days, and ECG waveforms and heart rate variability were analyzed. Furthermore, 1.25 mg/kg colchicine or vehicle was injected for 1 or 2 consecutive days in other rats at 6 weeks of age. One day after the final dosing, heart and blood samples were taken for histopathological and bloodchemical examination. ECG analysis revealed a prolonged RR interval, QRS duration, PR interval and QT interval. Heart rate variability analysis showed an increase in high frequency (HF) components as an index of parasympathetic nervous activity. In blood chemical examinations, colchicine induced high levels of parameters of cardiac injury and low levels and/or variations in Ca, inorganic phosphorus, potassium and chloride. Histopathologically, colchicine-treated rats showed eosinophilic granular degeneration and cytoplasmic vacuolation of ventricular myocardial cells but no remarkable change in the atrioventricular node. Not only blood chemical and histopathological changes but also ECG changes were induced in colchicine-treated rats, which indicated a decrease in myocardium excitability and conductivity, and these changes might be related to increased parasympathetic nervous activity and low blood Ca levels.

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Histopathological studies of microtubule disassembling agent-induced myocardial lesions in rats

Cited by 17 publications

References 21 publications

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

Coronary Spasm after an Injection of Vincristine

Cardiotoxic Changes of Colchicine Intoxication in Rats: Electrocardiographic, Histopathological and Blood Chemical Analysis

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