Potential of Naringin in the Prevention of Sweetened Alcohol-Induced Cardiometabolic Derangements in Adolescent Sprague-Dawley Rats

Abstract

Sweetened alcohol is one of the most consumed alcoholic beverages worldwide, and is gradually getting more popular, especially among adolescents and young adults. The rising consumption of sweetened alcohol necessitates research into the double burden of high sugar and alcohol intake on cardiometabolic health and the development of natural interventions to mitigate these outcomes. Naringin is a flavonoid phytochemical and a key ingredient in grapefruit, tomatoes, and other citrus fruits. It has been associated with various biological benefits, including the prevention and treatment of cardiometabolic diseases. This study aimed to determine the effects of naringin on sweetened alcohol-induced cardiometabolic derangements in adolescent male and female Sprague-Dawley rats. Eighty, 42-day-old (40 males, 40 females) Sprague-Dawley rats sourced from the Wits Research Animal Facility were randomly allocated to one of four treatment groups, with n = 20 rats in each group (10 males and 10 females), as follows: Control group: received plain gelatine (0.5% fructose in gelatine). Sweetened alcohol (SOH) group: received sweetened alcohol (20% fructose + 10% ethanol) in gelatine. Naringin (NA) group: received naringin (at 50mg/kg/day) in gelatine. Sweetened alcohol + naringin (SOH+NA) group: received sweetened alcohol + naringin (20% fructose + 10% ethanol + 50mg/kg/day naringin) in gelatine. The rats were freely allowed to eat all the treatments made available in wide-mouth glass containers and were given once daily at 10ml per 100g body weight for ten weeks. Body mass was recorded daily, food and water intake were recorded weekly, visceral fat mass, fasting blood glucose (FBG), serum triglyceride, and serum insulin, were measured at termination to assess different metabolic derangements. Serum neutrophil-gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), were also measured to assess kidney function. ix Cardiac function (left ventricular systolic and diastolic function) was assessed using echocardiography, along with blood pressure measurements to assess hypertension, as well as serum cardiac troponin-I concentrations, to assess myocyte damage. Histology of the liver, kidney, and heart using H&E stain was performed to determine hepatic steatosis in the liver, nephropathy indicators including glomerular urinary space, renal corpuscular area, glomerular tuft area, and glomerular density in the kidney, and left ventricular cardiomyocyte diameters in the heart and Picrosirius red stain to determine collagen deposition (collagen area fraction) in the heart. Rats on sweetened alcohol had decreased (p<0.05) food intake (standard rat chow) in both sexes. Male rats that consumed sweetened alcohol had increased (p<0.05) terminal body mass, while female rats that consumed sweetened alcohol had increased (p<0.05) visceral fat mass. Sweetened alcohol caused concentric remodelling, impaired left ventricular relaxation, and increased filling pressures in females (p<0.05). Male and female rats that consumed sweetened alcohol had increased (p<0.05) hepatic steatosis (fatty liver). In male rats, sweetened alcohol led to decreased (p<0.05) serum NGAL, KIM-1, and glomerular urinary space, while in female rats, consumption of sweetened alcohol led to decreased (p<0.05) serum NGAL, increased (p<0.05) KIM-1 concentration, and increased (p<0.05) glomerular density (early features of nephropathy). Naringin supplementation had no effects on food intake, body mass, visceral fat mass, or general cardiometabolic health in both male and female rats (p>0.05). However, naringin improved (p<0.05) concentric remodelling and decreased (p<0.05) serum TG, serum NGAL, and KIM-1 in females, while in males naringin caused decreased (p<0.05) serum NGAL and increased (p<0.05) serum KIM-1 concentrations. When x supplemented with sweetened alcohol, naringin led to decreased (p<0.05) serum insulin, increased (p<0.05) FBG, increased (p<0.05) glomerular density, and increased serum (p<0.05) KIM-1 in females, while in males, it led to increased (p<0.05) serum KIM-1 and NGAL concentrations. This study highlighted sexually dimorphic effects of sweetened alcohol consumption and naringin supplementation on cardiometabolic derangements. Female rats were more prone to sweetened alcohol-induced cardiometabolic derangements. While naringin supplementation has the potential to ameliorate some cardiometabolic dysfunctions. Naringin may negatively affect kidney functions when supplemented with sweetened alcohol. Further research will be necessary to evaluate molecular mechanism through which naringin supplemented with sweetened alcohol may negatively affect the kidney.