ABSTRACT
INTRODUCTION: Adolescents tend to experiment with ethanol which often results in heavy episodic drinking patterns leading to serious health concerns later in life. Chronic ethanol use damages renal tissue, promotes collagen deposition, and induces renal inflammation, thereby causing renal dysfunction. Therefore, an intervention such as simvastatin (a blood cholesterol-lowering drug) that could suppress the effects of ethanol on the kidney may be beneficial. This study explored the impact of simvastatin against the onset of renal morphological damage, fibrosis, and inflammation caused by ethanol exposure in mice. MATERIALS AND METHODS: Ten four-week old C57BL/6J mice (F = 5; M = 5) were assigned to each experimental group: (I) NT; no administration of ethanol or simvastatin; (II) EtOH; 2.5 g/kg/day of 20% ethanol; intraperitoneal injection (i.p.) (III) SIM; 5 mg/kg/day of simvastatin; orally (iv) EtOH + SIM5; 5 mg/kg/day of simvastatin, orally, followed by 2.5 g/kg/day of 20% ethanol; i.p. and (v) EtOH + SIM15; 15 mg/kg/day simvastatin, orally, followed by 2.5 g/kg/day of 20% ethanol; i.p. After the 28-day treatment period, the right kidney was removed and processed for haematoxylin and eosin staining, Masson's trichrome staining, or Tumour necrosis factor-alpha (TNF-α) immunohistochemistry. The renal corpuscular area, glomerular area, and urinary space area were measured and the area of collagen or TNF-α expression was quantified using ImageJ software. RESULTS: Ethanol administration significantly increased the renal corpuscular area, the glomerular area, the area of collagen, and the area of tissue with TNF-α immunoreactivity but decreased the area of urinary space. Simvastatin generally suppressed the ethanol effects in both sexes, although to varying degrees. CONCLUSIONS: Simvastatin proved to suppress collagen deposition and the TNF-α production induced by ethanol in the kidney of mice thus indicating its effectiveness in the treatment of ethanol-related renal diseases.
ABSTRACT
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.
