School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg, 2193, Republic of South Africa.
Cardiovasc Toxicol. 2024 Jan;24(1):15-26. doi: 10.1007/s12012-023-09821-6. Epub 2024 Jan 23.
Alcohol abuse by adolescents is becoming a serious health concern as they often progress to becoming alcoholics later in life which may lead to heart problems. Chronic alcohol use alters the cardiac function and structure, such as haemodynamic changes, weakening and loss of cardiomyocytes, myocardial fibrosis, and inflammation. Simvastatin is a commonly used drug for the treatment and management of various cardiovascular problems but information on its protective effects against alcohol-induced cardiomyocyte hypertrophy, fibrosis, and inflammation is lacking in the literature. Four-week-old male (n = 5) and female (n = 5) C57BL/6 J mice were assigned to each experimental group: (I) NT-no administration of alcohol or Simvastatin; (II) ALC-2.5 g/Kg/day of 20% alcohol via intraperitoneal injection (i.p.); (III) SIM-5 mg/Kg/day of Simvastatin via oral gavage; (iv) ALC + SIM5-5 mg/Kg/day of Simvastatin via oral gavage followed by 2.5 g/Kg/day of 20% alcohol via i.p.; and (v) ALC + SIM15-15 mg/Kg/day Simvastatin via oral gavage followed by 2.5 g/Kg/day of 20% alcohol via i.p. After the 28-day treatment period, the heart was removed and processed for H&E, Masson's trichrome, or TNF-α immunolabelling. The area and diameter of cardiomyocytes were measured on the H&E-stained sections. The distribution of collagen or TNF-α expression was quantified using the deconvolution tool of ImageJ software. The results confirmed alcohol-induced toxicity on the cardiomyocytes and Simvastatin reduced alcohol-induced cardiomyocyte hypertrophy, fibrosis, and inflammation in both sexes. This study demonstrated that Simvastatin, an FDA approved and easily accessible drug, may be beneficial in lowering the prevalence of alcohol-induced cardiovascular diseases (especially in adolescents) which will have a huge financial implication on health systems worldwide.
青少年酗酒正成为一个严重的健康问题,因为他们在以后的生活中往往会发展成酗酒者,这可能导致心脏问题。慢性酒精使用会改变心脏功能和结构,例如血流动力学变化、心肌细胞减弱和丧失、心肌纤维化和炎症。辛伐他汀是一种常用于治疗和管理各种心血管问题的药物,但关于其预防酒精诱导的心肌细胞肥大、纤维化和炎症的保护作用的信息在文献中缺乏。将四周龄雄性(n=5)和雌性(n=5)C57BL/6J 小鼠分配到每个实验组:(I)NT-不给予酒精或辛伐他汀;(II)ALC-每天腹腔注射 2.5g/kg 20%酒精;(III)SIM-每天口服 5mg/kg 辛伐他汀;(IV)ALC+SIM5-每天口服 5mg/kg 辛伐他汀,然后腹腔注射 2.5g/kg 20%酒精;(v)ALC+SIM15-每天口服 15mg/kg 辛伐他汀,然后腹腔注射 2.5g/kg 20%酒精。在 28 天的治疗期后,取出心脏并进行 H&E、Masson 三色或 TNF-α免疫标记。在 H&E 染色切片上测量心肌细胞的面积和直径。使用 ImageJ 软件的反卷积工具量化胶原或 TNF-α表达的分布。结果证实酒精对心肌细胞有毒性,辛伐他汀可减少酒精诱导的雄性和雌性心肌细胞肥大、纤维化和炎症。这项研究表明,辛伐他汀是一种 FDA 批准的、易于获得的药物,可能有助于降低酒精引起的心血管疾病(特别是青少年)的患病率,这将对全球卫生系统产生巨大的财务影响。