Pitavastatin-induced cholesterol deficiency elevates serum biomarkers associated with statin-related adverse effects in rats

Background: Statins are prescribed to manage hypercholesterolemia. While effective, these medications are associated with adverse effects, particularly myopathy. Cholesterol is essential for muscle function, and its depletion - especially by lipophilic statins - may contribute to muscle damage. Pitavastatin mainly targets hepatic Cholesterol synthesis with minimal direct effect on muscle tissue. This study investigates the impact of pitavastatin-induced Cholesterol depletion on skeletal muscle.

Methods: Male Sprague-Dawley rats were divided into three groups: control (n = 10), pitavastatin-treated on a normal diet (ND, n = 10), and pitavastatin-treated on a high-cholesterol diet (HCD, n = 10). Pitavastatin (15 mg/kg/day) was administered orally for 6 weeks. Serum lipid profile, hepatic injury markers (alanine aminotransferase, aspartate aminotransferase), muscle damage markers (creatine phosphokinase), and bone metabolism indicators (Alkaline Phosphatase, calcium, phosphate, or magnesium) were analyzed.

Results: Pitavastatin significantly reduced total Cholesterol and low-density lipoprotein Cholesterol in both ND and HCD groups (P < 0.05) without affecting triglycerides, high-density lipoprotein Cholesterol, or very-low-density lipoprotein. The ND group showed significant elevations in alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase compared to the control and HCD groups (P < 0.05), suggesting Cholesterol depletion contributes to hepatic and muscle damage. The HCD group exhibited reduced elevations in these markers, indicating a protective role of dietary Cholesterol. No significant differences were observed in Alkaline Phosphatase, calcium, phosphate, or magnesium. Bivariate correlation analysis showed an inverse association between total Cholesterol and liver enzyme markers.

Conclusion: Pitavastatin-induced Cholesterol depletion increased hepatic and muscle damage markers. Dietary Cholesterol may mitigate these effects, highlighting the importance of Cholesterol homeostasis in statin therapy.

cholesterol; liver; myopathy; pitavastatin; statin.