Atorvastatin Mitigates Hypercholesterolemia-Induced Alterations in Cerebral Mitochondrial Dehydrogenases in Rats

Statins are widely used lipid-lowering agents for the prevention and treatment of cardiovascular disease. Atorvastatin, one of the most frequently used statins, was reported to influence mitochondrial function, including the regulation of mitochondrial enzyme activity. Our recent study demonstrated that short-term treatment with atorvastatin effectively counteracted the alterations in α-ketoglutarate dehydrogenase (α-KGDH) induced by a high-cholesterol diet. Since α-KGDH and isocitrate dehydrogenase (IDH) together with glutamate dehydrogenase (GDH) are functionally interconnected, we hypothesized that atorvastatin modulates their activity in the brain. The study aimed to evaluate the effect of short-term atorvastatin treatment on cerebral mitochondrial dehydrogenases α-KGDH, IDH and GDH in hypercholesterolemic rats. Atorvastatin at dose 20 mg/kg b·wt/day (HC+A, n = 8) or vehicle (HC, n = 8) were administered to HC rats for 3 weeks. The control group was fed a standard diet (ST, n = 8). α-KGDH activity and relative protein abundance of its subunits were evaluated. Similarly, IDH and GDH activities as well as their relative protein levels were determined. In addition, the level of cerebral glutamate was measured. The study showed that hypercholesterolemia induced elevation of α-KGDH and IDH activities and reduction in GDH activity and glutamate level. Treatment with atorvastatin mitigated these metabolic disturbances, highlighting its potentially favorable effect in the brain.