Protective effect of HMG CoA reductase inhibitors against running wheel activity induced fatigue, anxiety like behavior, oxidative stress and mitochondrial dysfunction in mice

Abstract

Background: Chronic fatigue stress (CFS) is an important health problem with unknown causes and unsatisfactory prevention strategies, often characterized by long-lasting and debilitating fatigue, myalgia, impairment of neuro-cognitive functions along with other common symptoms. The present study has been designed to explore the protective effect of statins against running wheel activity induced fatigue anxiety.

Methods: Male albino Laca mice (20-30 g) were subjected to swim stress induced fatigue in a running wheel activity apparatus. Atorvastatin (10, 20 mg/kg, po) and fluvastatin (5, 10 mg/kg, po) were administered daily for 21 days, one hour prior to the animals being subjected to running wheel activity test session of 6 min. Various behavioral tests (running wheel activity, locomotor activity and elevated plus maze test), biochemical parameters (lipid peroxidation, nitrite concentration, glutathione levels and catalase activity) and mitochondrial complex enzyme dysfunctions (complex I, II, III and IV) were subsequently assessed.

Results: Animals exposed to 6 min test session on running wheel for 21 days showed a significant decrease in number of wheel rotations per 6 min indicating fatigue stress like behavior. Treatment with atorvastatin (10 and 20 mg/kg) and fluvastatin (10 mg/kg) for 21 days significantly improved the behavioral alterations [increased number of wheel rotations and locomotor activity, and anxiety like behavior (decreased number of entries and time spent in open arm)], oxidative defence and mitochondrial complex enzyme activities in brain.

Conclusion: Present study suggests the protective role of statins against chronic fatigue induced behavioral, biochemical and mitochondrial dysfunctions.