Atorvastatin alleviates oxidative damage by activating the nuclear factor erythroid 2-related factor 2 pathway after brain ischemia in mice

Abstract

Background: Exploring anti-oxidative stress drugs are essential to prevent and treat ischemic cerebral infarction. The present study was designed to explore the antioxidant molecular mechanism of atorvastatin underlying ischemic cerebral infarction.Methods: Male, Nrf2+/+ and Nrf2−/− mice were subjected to distal middle cerebral artery occlusion (dMCAO). Mice were treated with atorvastatin or vehicle daily for 7 days before surgery until sampling or continuous administration 3 days after surgery. Motor function was measured before and after surgery at 24, 48 and 72 h respectively. The brain water content and infarct volume were monitored. ELISA, Western blot, and immunofluorescence staining were used to analyze the expression of Nrf2 and autophagy-related proteins.Results: We found that 20 mg/kg atorvastatin significantly improved the neurological impairment of mice, reduced the volume of cerebral infarction, rescued cerebral edema, and showed a protective effect on the brain. Compared with vehicle administration, atorvastatin-treated mice potently significantly attenuated oxidative damage and promoted Nrf2 nuclear translocation after dMCAO in Nrf2+/+ mice. While atorvastatin's anti-oxidative damage role was invalided in the Nrf2−/− mice. Atorvastatin up-regulated the expression of autophagy-related genes and might protect against oxidative stress by activating autophagy.Atorvastatin activated the Nrf2 signaling pathway and exerted an antioxidant activity, so as to improve the neurological function recovery of stroke in mice.Conclusions: Atorvastatin exhibited an antioxidant activity by activating Nrf2 signaling pathway and activating autophagy, so as to protect the brain from damage caused by dMCAO.

Potential protective effects of ginger and atorvastatin against diazinon-induced hepatotoxicity in rats: A comparative histopathological, immunohistochemical, and biochemical study

“…One of the statin medications most frequently prescribed for a variety of conditions is atorvastatin (ATR) (Demoz et al, 2019). ATR lowers LDL-cholesterol levels in patients with hyperlipidemia more effectively than other medications (Abdulwahab et al, 2021;Fan et al, 2022). ATR also has a variety of advantageous pharmacological effects, such as its anti-inflammatory and antioxidant properties, which manifest at low doses by inhibiting oxidative stress (Naeimi et al, 2017).…”