Muhammad Aliyu, Waziri Aliyu Dahiru, Forcados Gilead Ebiegberi, Sanusi Babangida, Sani Hadiza, Malami Ibrahim, Abubakar Ibrahim Babangida, Oluwatoyin Habeebah Yahya, Adinoyi Otaru Abdulrasheed, Mohammed Hafsat Abdullahi
Department of Biochemistry, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Kaduna State, Nigeria.
Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria.
Heliyon. 2019 Jun 24;5(6):e01905. doi: 10.1016/j.heliyon.2019.e01905. eCollection 2019 Jun.
Sickle cell anaemia is a hereditary disease branded by an upsurge in generation of ROS, irregular iron release and little or no antioxidant activity which can lead to cellular injuries due to oxidative stress resulting in severe symptoms including anaemia and pain. The disease is caused by a mutated version of the gene that helps make haemoglobin, the protein that carries oxygen in red blood cells. We used and experiments to examine the antisickling effects of rutin for the first time by means of before and after induction approaches in sickle erythrocytes. Rutin was docked against deoxy-haemoglobin and 2,3-bisphosphoglycerate mutase, revealing binding energies (-27.329 and -25.614 kcal/mol) and K of 0.989μM and 0.990 μM at their catalytic sites through strong hydrophobic and hydrogen bond interactions. Sickling was thereafter, induced at 3 h with 2% metabisulphite. Rutin prevented sickling maximally at 12.3μM and reversed same at 16.4μM, by 78.5% and 69.9%, one-to-one. Treatment with rutin significantly (P < 0.05) reinvented the integrity of erythrocytes membrane as evident from the practical % haemolysis compared to induced erythrocytes. Rutin also significantly (P < 0.05) prevented and reversed lipid peroxidation relative to untreated. Likewise, GSH, CAT levels were observed to significantly (P < 0.05) increase with concomitant significant (P < 0.05) decrease in SOD activity based on administration of rutin after sickling induction approach. Furthermore, FTIR results showed that treatment with rutin favourably altered the functional chemistry, umpiring from shifts and functional groups observed. It can thus be deduced that, antisickling effects of rutin may be associated with modulation of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, alteration of redox homeostasis and functional chemistry of sickle erythrocytes.
镰状细胞贫血是一种遗传性疾病，其特征是活性氧生成增加、铁释放异常以及抗氧化活性微弱或缺失，这会因氧化应激导致细胞损伤，进而引发包括贫血和疼痛在内的严重症状。该疾病由一个发生突变的基因引起，该基因有助于生成血红蛋白，即红细胞中携带氧气的蛋白质。我们首次通过镰状红细胞诱导前后的方法，利用[具体实验方法1]和[具体实验方法2]实验来研究芦丁的抗镰状细胞作用。芦丁与脱氧血红蛋白和2,3-二磷酸甘油酸变位酶对接，通过强烈的疏水和氢键相互作用，在其催化位点显示出结合能（-27.329和-25.614千卡/摩尔）以及K值分别为0.989微摩尔和0.990微摩尔。此后，在3小时时用2%的焦亚硫酸钠诱导镰状化。芦丁在12.3微摩尔时最大程度地预防了镰状化，在16.4微摩尔时使镰状化逆转，一对一情况下分别逆转了78.5%和69.9%。与诱导红细胞相比，从实际溶血百分比来看，芦丁处理显著（P < 0.05）恢复了红细胞膜的完整性。相对于未处理的情况，芦丁还显著（P < 0.05）预防并逆转了脂质过氧化。同样，基于镰状化诱导后给予芦丁，观察到谷胱甘肽（GSH）、过氧化氢酶（CAT）水平显著（P < 0.05）升高，同时超氧化物歧化酶（SOD）活性显著（P < 0.05）降低。此外，傅里叶变换红外光谱（FTIR）结果表明，芦丁处理有利地改变了功能化学，这从观察到的位移和官能团可以判断。因此可以推断，芦丁的抗镰状细胞作用可能与脱氧血红蛋白、2,3-二磷酸甘油酸变位酶的调节、氧化还原稳态的改变以及镰状红细胞的功能化学有关。
