Protective Effects of Policosanol and Atorvastatin Co-Supplementation Against High-Cholesterol and High-Galactose Diet-Induced Metabolic and Organ Dysfunction in Zebrafish

The study compares the effects of policosanol (Poli), atorvastatin (Ator), and their combination (Poli+Ator) in mitigating high-cholesterol and high-galactose (HCHG) diet-induced metabolic stress and organ damage in zebrafish. After 22 weeks of feeding, the lowest survival probability was observed in the Ator-supplemented group (0.64). In comparison, the Poli and Poli+Ator-supplemented groups showed higher survival probabilities of 0.76 and 0.71, respectively. Compared with Poli, Ator supplementation had a greater effect in mitigating HCHG-induced dyslipidemia. Nonetheless, Poli+Ator demonstrated a significantly greater effect than Ator and Poli in reducing total blood cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and in elevating the HDL-C/TC ratio. No significant effect of Ator supplementation was observed on the HCHG-induced elevations in blood glucose and malondialdehyde (MDA) levels or the diminished sulfhydryl content; however, Poli alone and Poli+Ator significantly improved blood glucose, MDA, and sulfhydryl content. Consistently, the non-significant effect of Ator on the amputated tail fin regeneration was substantially improved by the Poli+Ator supplementation. In addition, Poli and Poli+Ator markedly reduce liver steatosis, neutrophil infiltration, and interleukin (IL)-6 production, while inhibiting the generation of oxidative species and senescent-positive cells in the kidney and preventing intestinal fibrosis. Also, Poli and Poli+Ator substantially minimize HCHG-triggered oxidative stress in reproductive organs, enhance spermatozoa count in the testis and substantially improve the embryo-producing ability of zebrafish. The study outlines the beneficial effect of Poli and Poli+Ator in mitigating HCHG-induced dyslipidemia, organ damage, and reproductive health.