Yıldırım Erkan, Yıldırım Nilgun, Cengiz Mahir, Yazıcı Gulce Naz, Coskun Resit, Suleyman Bahadır, Coban Abdulkadir, Suleyman Halis
Department of Cardiology, Life Hospital, Elazıg, Turkey.
Department of Medical Oncology, Firat University Faculty of Medicine, Elazıg, Turkey.
Biotech Histochem. 2023 Apr;98(3):193-200. doi: 10.1080/10520295.2022.2153385. Epub 2022 Dec 9.
Bevacizumab is a recombinant humanized monoclonal antibody whose adverse effects include cardiotoxicity. We investigated whether using adenosine triphosphate (ATP) or benidipine either separately or together protects against cardiac damage induced by bevacizumab in rats. Forty Wistar albino male rats were allocated to five groups of eight: bevacizumab (Bv), ATP + bevacizumab (ABv), benidipine + bevacizumab (BBv), ATP + benidipine + bevacizumab (ABBv) and untreated controls. Rats in the ABv group were injected intraperitoneally (i.p.) with 2 mg/kg ATP. The BBv group was given 4 mg/kg benidipine by oral gavage. The ABBv group was injected i.p. with 2 mg/kg ATP and simultaneously administered 4 mg/kg benidipine orally. One hour after administration of ATP, benidipine or normal saline, the Bv, ABv, BBv and ABBv groups were injected i.p. with 10 mg/kg bevacizumab. Malondialdehyde (MDA) and total glutathione (tGSH) levels were measured in cardiac tissue, and troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in blood samples. Tissue samples were examined for histopathology. We found the lowest TP I, CK-MB and MDA levels and the highest tGSH level in the ABBv group; these results were similar to the control group. Nuclei of cardiomyocytes in the BV group were misshapen and shrunken, and myofibers were disrupted; we also observed eosinophilic degeneration and interstitial edema. Blood capillaries were dilated and congested. We observed amelioration of these findings in the ABBv group. We found that ATP and benidipine alone or in combination reduced cardiac damage associated with the use of bevacizumab. ATP + benidipine combined therapy produced the most favorable results.
贝伐单抗是一种重组人源化单克隆抗体，其不良反应包括心脏毒性。我们研究了单独或联合使用三磷酸腺苷（ATP）或贝尼地平是否能预防贝伐单抗诱导的大鼠心脏损伤。将40只雄性Wistar白化大鼠分为五组，每组8只：贝伐单抗组（Bv）、ATP + 贝伐单抗组（ABv）、贝尼地平 + 贝伐单抗组（BBv）、ATP + 贝尼地平 + 贝伐单抗组（ABBv）和未治疗的对照组。ABv组大鼠腹腔注射（i.p.）2 mg/kg ATP。BBv组通过口服灌胃给予4 mg/kg贝尼地平。ABBv组腹腔注射2 mg/kg ATP并同时口服给予4 mg/kg贝尼地平。在给予ATP、贝尼地平或生理盐水1小时后，Bv、ABv、BBv和ABBv组腹腔注射10 mg/kg贝伐单抗。测定心脏组织中的丙二醛（MDA）和总谷胱甘肽（tGSH）水平，并测定血液样本中的肌钙蛋白I（TP I）和肌酸激酶MB（CK-MB）水平。对组织样本进行组织病理学检查。我们发现ABBv组的TP I、CK-MB和MDA水平最低，tGSH水平最高；这些结果与对照组相似。Bv组心肌细胞核畸形、缩小，肌纤维断裂；我们还观察到嗜酸性变性和间质水肿。毛细血管扩张和充血。我们在ABBv组中观察到这些发现有所改善。我们发现单独或联合使用ATP和贝尼地平可减少与使用贝伐单抗相关的心脏损伤。ATP + 贝尼地平联合治疗产生了最有利的结果。
