Atorvastatin ameliorates α-KGDH and GDH functions in rats with diet-induced hypercholesterolemia

Background

α-ketoglutarate dehydrogenase complex (α-KGDH) belongs to mitochondrial 2-oxoacid dehydrogenases family and is the key regulatory enzyme of cell metabolism. It is functionally interconnected with glutamate dehydrogenase (GDH) which is a source of α-KG, a substrate for α-KGDH. Our previous studies demonstrated that simvastatin had an influence on 2-oxoacid dehydrogenases, including α-KGDH. Hence, we hypothesised that atorvastatin, one of the most commonly prescribed lipid-lowering drugs, may modify liver α-KGDH and GDH.

Objectives

The purpose of the present study was to evaluate the effect of atorvastatin on liver α-KGDH and GDH in rats with diet-induced hypercholesterolemia.

Methods

Atorvastatin at dose 20 mg/kg b.wt. (HC + A group, n = 10) or vehicle (HC group, hypercholesterolemic control, n = 10) were administered to rats with hypercholesterolemia for 21 days. The normal control group was fed a standard diet (ST group, normal control, n = 10). α-KGDH and GDH activities as well as their protein levels were determined. Moreover, serum parameters of lipid profile and liver function were measured.

Results

Liver α-KGDH and GDH activities were lower in HC than in ST rats. Atorvastatin enhanced the inhibited activities of α-KGDH and GDH. Stimulation of α-KGDH and GDH by atorvastatin did not correspond with the increase in protein levels of these enzymes indicating that atorvastatin activated α-KGDH and GDH most likely via post-translational mechanism. Atorvastatin had a beneficial effect on serum lipid profile and did not change the parameters of liver function.

Conclusion

The present study demonstrated that atorvastatin ameliorated liver α-KGDH and GDH functions in rats with diet-induced hypercholesterolemia.