The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats

Aldemir, Mehmet Naci; Şimşek, Melih; Kara, Ali Veysel; Özçıçek, Fatih; Mammadov, Renad; Yazıcı, Gülce Naz; Sunar, Mukadder; Coskun, Resit; Gülaboğlu, Mine; Süleyman, Halis

doi:10.1177/0960327120909874

Cited by 10 publications

(8 citation statements)

References 47 publications

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“…The results obtained in the present study show that treatment with vincristine causes a significant increase in the expressions of TNFα, eNOS, iNOS, and connexin 43 in the cardiac tissue of animals. Similar results have been obtained with other antitumor drugs such as doxorubicin ( Lim, 2013 ; Bin Jardan et al, 2020 ; Birari et al, 2020 ), sunitinib ( Aldemir et al, 2020 ), and cisplatin ( El-Hawwary and Omar, 2019 ). On the other hand, enhanced oxidative stress, inflammation, and upregulation of TNFα, interleukin-6 (IL-6), and interleukin-10 (IL-10) have been associated with vincristine-induced neurotoxicity of the peripheral nervous system ( Gong et al, 2016 ; Vashistha et al, 2017 ; Qin et al, 2020 ; Geisler, 2021 ).…”

Section: Discussionsupporting

confidence: 83%

Cardiovascular Toxicity Induced by Chronic Vincristine Treatment

Herradón

González

et al. 2021

Front. Pharmacol.

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Vincristine is an effective anticancer agent for treating leukemias, lymphomas, and other solid tumors. Vincristine’s better-known severe side effects include bone marrow depression, hyponatremia, peripheral neuropathy, and gastrointestinal distress. In recent years, cardiovascular damage also has been described during vincristine treatments. However, the vascular toxicity induced by vincristine is little studied. The aim of the present is to evaluate whether these alterations remain after the suspension of chemotherapy treatment (sequelae) and the possible mechanisms involved in this vascular damage. Adult male Wistar rats were used. The animals were divided into four treatment groups: two groups of saline (0.9% NaCl; saline, sequelae saline) and two groups of vincristine (100 μg/kg; vincristine, sequelae vincristine). Saline or vincristine was administered intraperitoneally in two cycles of 5 days each, leaving a rest period between cycles of 2 days. The final cumulative vincristine dose administered was 1 mg/kg. Sequelae groups correspond to 2 weeks after stopping treatment with the antitumor agent. At the end of the different experimental protocols, cardiac and vascular functions were analyzed. Alterations in the expression of different proteins in the cardiovascular tissues were also investigated. Chronic treatment with vincristine did not produce significant changes in basal cardiac function but provoked significant endothelial dysfunction in the aorta and a significant decrease in the mesenteric contractile function. These cardiovascular functional alterations disappeared 2 weeks after the suspension of chemotherapy treatment. Vincristine treatment caused a significant increase in the expression of tumor necrosis factor-alpha (TNFα), endothelial and inducible nitric oxide synthases (eNOS and iNOS), and connexin 43 in cardiac tissue. In the aorta, the chronic treatment with vincristine caused a slight non-significant increase in TNFα expression, a significant increase in eNOS and iNOS, and a significant decrease in connexin 43. After 2 weeks of vincristine treatment (sequelae group), the expression of TNFα increased and eNOS and iNOS expressions disappeared, but a significant decrease in the expression of connexin 43 was still observed in the aorta. In mesenteric arteries, similar data to those found in the aorta were observed. In conclusion, chronic treatment with vincristine causes functional alterations in the vascular function of both conductance and resistance vessels and changes in the expressions of TNFα, eNOS, iNOS, and connexin 43 in cardiovascular tissues, implicating direct toxicity during its treatment. These functional alterations are transitory and disappear after the suspension of its treatment.

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Section: Discussionsupporting

confidence: 83%

Cardiovascular Toxicity Induced by Chronic Vincristine Treatment

Herradón

González

et al. 2021

Front. Pharmacol.

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“…TP-I is used as a sensitive marker for myocardial damage confirmation in coronary artery disease [32]. Studies have shown that oxidative stress-induced damage to the myocardial cell membrane causes TP-I release into the circulation, as in coronary artery disease [16,33]. The current study results determined that TP-I levels were higher in ATR group animals' blood serum than in AAT.…”

Section: Discussionmentioning

confidence: 48%

“…In the literature review, no studies were found investigating the effect of ATP particularly on atorvastatin-induced oxidative heart damage. However, ATP treatment showed a favorable impact against sunitinib-induced oxidative heart damage by reducing the level of MDA and preventing excessive reduction of tGSH [16].…”

Section: Discussionmentioning

confidence: 98%

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Adenosine Triphosphate Exerts Cardioprotective Effect on High-Dose Atorvastatin-Induced Heart Damage in Rats

Coskun

2022

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi

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Atorvastatin is a statin derivated hypolipidemic drug used in the treatment of hyperlipidemia. High-dose atorvastatin has been shown to significantly reduce adenosine triphosphate (ATP) levels in the heart tissue. Reduction of ATP by atorvastatin causes increased production of reactive oxygen species (ROS), decreased antioxidants, subsequent cell membrane and mitochondrial damage. The present study aimed to biochemically investigate the protective effect of ATP against possible cardiac damage caused by high dose atorvastatin in rats. Male Wistar rats were divided into atorvastatin (ATR), atorvastatin+ATP (AAT) and healthy control (HG) groups. ATP at a 25 mg/kg dose was injected intraperitoneally (ip) to the AAT (n-6) group. 0.9% NaCl as solvent was applied to the ATR (n-6) and HG (n-6) groups by the same route. Afterward, atorvastatin was administered orally at a dose of 20 mg/kg to the AAT and ATR groups. This procedure was repeated once daily for four weeks. At the end of this period, blood samples were taken into tubes to analyze troponin-I (TP-I) by cardiac puncture before animals were sacrificed with high-dose anesthesia. In addition, heart tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), total oxidant (TOS) and total antioxidant (TAS) levels were measured. Biochemical test results showed that in the heart tissues of the ATR group, the oxidative parameters MDA and TOS significantly increased, while the antioxidant parameters tGSH and TAS significantly decreased compared to AAT and HG. Atorvastatin alone administration significantly increased blood TP-I levels, a marker of cardiac tissue damage. However, ATP administration to AAT group animals brought oxidative parameter levels closer to HG, despite high-dose atorvastatin treatment. In addition, the significant decrease in antioxidant levels was prevented by ATP application. High doses of atorvastatin can cause heart damage. ATP treatment was able to prevent atorvastatin-induced oxidative heart damage.

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“…27 It has also been found that VEGF inhibition is accountable for the oxidative heart and dermal damage associated with tyrosine kinase inhibitors (target-driven anticancer drugs), and that this damage was minimized by the administration of ATP. 28,29 The current biochemical and histopathological results show that the oxidative renal damage associated with bevacizumab is also suppressed by benidipine. As stated above, benidipine is a Ca 2+ channel blocker drug with antioxidant properties.…”

Section: Discussionmentioning

confidence: 75%