Ajibade Temitayo Olabisi, Oyagbemi Ademola Adetokunbo, Durotoye Ladoke A, Omóbòwálé Temidayo Olutayo, Asenuga Ebunoluwa Racheal, Olayemi Funsho Olakitike
J Complement Integr Med. 2017 Mar 1;14(1). doi: 10.1515/jcim-2015-0082.
Background Phenylhydrazine (PHE) in experimental animal models has been widely reported to cause haemolytic anaemia, via the induction of oxidative stress and thus causing deleterious cardiovascular complications. Hence, this study was designed to evaluate the possible modulatory role of melatonin (MLT) or vitamin C when co-administered with PHE. Methods Anaemia was established with PHE administration. MLT or vitamin C was co-administered with PHE. Haematological parameters, markers of oxidative stress, enzymic and non-enzymic antioxidants, blood pressure and electrocardiograms were assessed. Results PHE administration led to a significant (p<0.05) increase in malondialdehyde (MDA), and hydrogen peroxide (H2O2) generated in cardiac, renal and red blood cell (RBC) lysates. PHE also significantly reduced the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione (GSH) contents, respectively. The RBC counts, haemoglobin (Hb) concentration and packed cell volume (PCV) were also significantly reduced following the administration of PHE. Furthermore, the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MABP) increased significantly in rats administered PHE alone. Similarly, PHE administration led to a significant drop in heart rate but prolonged QRS, QT and QTc interval. Pathology of the heart and kidney was also observed in PHE treated group. However, treatment with MLT and vitamin C improved enzymic and non-enzymic antioxidant system together with the restoration of SBP, DBP and MABP to near normal. The architectural anarchy observed in the heart and kidney of PHE administered rats was reversed to some extent. Conclusions Hence, MLT and vitamin C could be employed as therapeutic targets in various cardiovascular diseases and its complications.
背景 在实验动物模型中，苯肼（PHE）已被广泛报道可通过诱导氧化应激从而导致有害的心血管并发症，进而引发溶血性贫血。因此，本研究旨在评估褪黑素（MLT）或维生素C与PHE联合使用时可能的调节作用。方法 通过给予PHE建立贫血模型。将MLT或维生素C与PHE联合使用。评估血液学参数、氧化应激标志物、酶性和非酶性抗氧化剂、血压和心电图。结果 给予PHE导致心脏、肾脏和红细胞（RBC）裂解物中丙二醛（MDA）和过氧化氢（H2O2）显著（p<0.05）增加。PHE还分别显著降低了谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）的活性以及还原型谷胱甘肽（GSH）的含量。给予PHE后，红细胞计数、血红蛋白（Hb）浓度和血细胞比容（PCV）也显著降低。此外，单独给予PHE的大鼠收缩压（SBP）、舒张压（DBP）和平均动脉血压（MABP）显著升高。同样，给予PHE导致心率显著下降，但QRS、QT和QTc间期延长。在PHE治疗组中也观察到心脏和肾脏的病理变化。然而，MLT和维生素C治疗改善了酶性和非酶性抗氧化系统，同时使SBP、DBP和MABP恢复到接近正常水平。在给予PHE的大鼠心脏和肾脏中观察到的结构紊乱在一定程度上得到了逆转。结论 因此，MLT和维生素C可作为各种心血管疾病及其并发症的治疗靶点。
