Combination of Policosanol (Raydel®) and Atorvastatin Improve High-Density Lipoproteins and Antioxidant Abilities to Protect Vital Organs and Fertility in Hyperlipidemic/Hyperglycemic Zebrafish

<b>Objectives:</b> The study explores the comparative effects of atorvastatin (ATV), policosanol (PCO), and their combination (ATV+PCO) on metabolic stress and associated organ damage in hyperlipidemic-hyperglycemic zebrafish. <b>Methodology:</b> Hyperlipidemic-hyperglycemic zebrafish (<i>n</i> = 112) were segregated into four groups (<i>n</i> = 28/group) and fed either with a high-cholesterol (HC, 4% <i>w</i>/<i>w</i>) and a high-galactose (HG, 30% <i>w</i>/<i>w</i>) diet, HCHG diet with policosanol (PCO, 0.1% <i>w</i>/<i>w</i>), atorvastatin (ATV, 0.1% <i>w</i>/<i>w</i>), or ATV+PCO (0.1% <i>w</i>/<i>w</i> each). After 12 weeks of supplementation, survivability and embryo production were assessed, along with biochemical and histological examinations of various organs across the groups. <b>Results:</b> Following a 12-week dietary regime, compromised zebrafish survival probability (0.75) was observed in the ATV group, compared to the PCO group (0.89), which increased to 0.82 with combined intake of ATV+PCO. A significantly greater effect of ATV than PCO was observed in reducing the HCHG elevated TC, TG, and LDL-C levels. However, compared to the ATV, a significantly higher HDL-C/TC (%) ratio was spotted in the PCO. Unlike individual supplementation (ATV or PCO), a combined intake (ATV+PCO) proved highly effective in counteracting dyslipidemia, especially by augmenting the HDL-C/TC (%) ratio. Interestingly, no protective effect of ATV was observed against elevated blood glucose levels, oxidative stress, or diminished antioxidant markers. Whereas ATV, in combination with PCO, significantly reduced blood glucose and MDA levels and elevated sulfhydryl content and antioxidant variables (ferric iron reduction ability and paraoxonase activity). ATV+PCO supplementation effectively mitigated HCHG-induced fatty liver, inflammation, ROS generation in the kidney, and brain senescence. Likewise, ATV+PCO improved reproductive health, elevating spermatozoa counts and embryo production ability of zebrafish. Notably, ATV+PCO supplementation significantly inhibited the HCHG-induced eye damage and demyelination in the retina, while ATV alone failed to establish any such changes. <b>Conclusions:</b> The study indicates the combinational therapy of ATV+PCO may offer a possible treatment to counter the metabolic stress and associated events in hyperlipidemic-hyperglycemic zebrafish.