Effects of Different Atorvastatin Doses on Immunohistochemical Markers in the Hippocampus of Male Adult Rats

Abstract

Statins, beyond their lipid lowering role, exert beneficial effect by acting as a neuroprotective agent in some clinical cases such as brain injury, stroke, ischemia, seizures and Alzheimer’s disease. The aim of this study is toinvestigate the effects of different oral doses of atorvastatin on normal male rats, via studying immunohistochemical markers in the hippocampus. Twenty-four adult male Wistar rats were used in the experiment. They were obtained from the animal house (at Department of Pharmacology & Toxicology, College of Pharmacy/ Al-Mustansiriya University). Animals are divided into 4 groups randomly each group contains 6 animals as follow: Group 1: Animals are administered saline orally for 30 days and serve as (control group), Group 2: Animals are administered 5 mg/kg/day Atorvastatin in the form of oral suspension for 30 days, Group 3: Animals are administered 10mg/kg/day Atorvastatin for 30 days, Group 4: Animals are administered 20 mg/kg/day Atorvastatin for 30 days. All animals in this study were dissected under anesthesia; heads were decapitated for extraction of the brain. Immunohistochemical method was used to evaluate the expression of Glial Fibrillary Acidic Protein, Glutathione Reductase and neuronal Nitric Oxide Synthase markers in the rat’s hippocampus. There was a significant reduction of GFAP expression in the group of rats treated with 20 mg/kg atorvastatin when compared with the control and 5 mg/kg atorvastatin. While, a significant increase in GR expression was noticed in the group treated with 20 mg/kg atorvastatin compared with other groups. Also, the results showed a significant reduction in nNOS expression in the hippocampus of rats treated with 20 mg/kg atorvastatin when compared with other groups. The present study demonstrates that atorvastatin exerts its neuroprotective effects in a 20 mg/kg dose, more than in 5 mg/kg or 10 mg/kg doses. The decreasing in astrocytes activity, promoting of anti-oxidant enzymes and reducing in nitrative stress were documented when a short term high atorvastatin dose used.

Keywords: hippocampus, atorvastatin, neuronal Nitric Oxide Synthase (nNOS), Glial Fibrillary Acidic Protein (GFAP), Glutathione Reductase (GR).