Mitoquinol mesylate ameliorates hematological aberration in cirrhotic-hepatocellular carcinogenic rats

L. Sulaimon, R. Adisa, F. Abdulkareem
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Abstract

Introduction: Hematological abnormalities such as anemia, neutropenia, and thrombocytopenia experienced by cancer patients undergoing chemotherapy necessitate the need to develop agents that stimulate erythropoiesis and boost immune response in cancer. Aim: The present study investigated the effects of mitoquinol mesylate (MitoQ) on the hematological profile of diethyl nitrosamine (DEN)-induced cirrhotic-hepatocellular carcinogenic (HCC) rats. Materials and Methods: One hundred Wistar strain albino rats were randomly divided into five groups (n = 20) for the experimental period of 20 weeks. Groups A, B, and C received distilled water, 10 mg/kg each of DEN and MitoQ respectively. Animals in Group D were pretreated with 10 mg/kg MitoQ for a week followed by coadministration of 10 mg/kg each of MitoQ and DEN for 20 weeks, while Group E received 10 mg/kg DEN for 8 weeks and then coadministration of 10 mg/kg each of DEN and MitoQ till the end of 20th week. Animals were sacrificed at the end of 12th, 16th, and 20th week. Blood samples were collected into labeled heparinized bottles for hematological analysis. Results: Administration of DEN significantly (P < 0.05) decreased the levels of red blood cell (RBC) count and erythrocytes indices. These erythrogram parameters were continuously deranging from 6.86 ± 0.26 to 2.69 ± 0.01, from 37.40 ± 1.99 to 30.35 ± 0.57, from 12.16 ± 0.97 to 8.90 ± 0.37 in the levels of RBC, packed cell volume, and hemoglobin, respectively, with the progression of HCC from cirrhosis to advanced HCC in Wistar rats. Further, the levels of white blood cells (WBCs, 3.68 ± 0.08), granulocytes (1.30 ± 0.06), lymphocytes (0.63 ± 0.11), and platelets (440.00 ± 22.67) were significantly reduced in the DEN group compared to healthy control (4.46 ± 0.12, 2.14 ± 0.27, 1.70 ± 0.13, and 685.80 ± 15.48 in the levels of WBC, granulocytes, lymphocytes, and platelets, respectively) at the advanced HCC stage. Interestingly, MitoQ interventions significantly (P < 0.05) reversed alterations in hematological indices induced by DEN toxicity. Conclusion: Our findings suggest that MitoQ is safe and capable of normalizing hematological abnormalities associated with cirrhosis and HCC in Wistar rats.
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甲磺酸米托喹啉改善肝硬化-肝细胞癌大鼠血液学失常
导论:接受化疗的癌症患者所经历的血液学异常,如贫血、中性粒细胞减少症和血小板减少症,需要开发刺激红细胞生成和增强癌症免疫反应的药物。目的:研究甲磺酸米托喹啉(MitoQ)对二乙基亚硝胺(DEN)诱导的肝硬化-肝细胞癌(HCC)大鼠血液学特征的影响。材料与方法:选用Wistar系白化大鼠100只,随机分为5组(n = 20),试验期20周。A、B、C组分别给予蒸馏水,DEN和MitoQ各10 mg/kg。D组先给予10 mg/kg MitoQ预处理1周,然后分别给药10 mg/kg MitoQ和DEN,连续20周;E组先给药10 mg/kg DEN,连续8周,再分别给药10 mg/kg DEN和MitoQ,直至第20周结束。于第12、16、20周末处死动物。血样采集到标记的肝素化瓶中进行血液学分析。结果:DEN可显著降低大鼠红细胞计数及红细胞指数(P < 0.05)。随着Wistar大鼠肝细胞癌由肝硬化发展到晚期,红细胞、堆积细胞体积、血红蛋白的红图参数分别在6.86±0.26 ~ 2.69±0.01、37.40±1.99 ~ 30.35±0.57、12.16±0.97 ~ 8.90±0.37范围内变化。此外,与健康对照组相比,DEN组肝癌晚期白细胞(WBC, 3.68±0.08)、粒细胞(1.30±0.06)、淋巴细胞(0.63±0.11)和血小板(440.00±22.67)水平(WBC、粒细胞、淋巴细胞和血小板水平分别为4.46±0.12、2.14±0.27、1.70±0.13和685.80±15.48)显著降低。有趣的是,MitoQ干预显著(P < 0.05)逆转了DEN毒性引起的血液学指标的改变。结论:我们的研究结果表明,MitoQ是安全的,能够使Wistar大鼠肝硬化和HCC相关的血液学异常正常化。
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