Rosuvastatin ameliorates chemically induced acute lung injury in rats by targeting ferroptosis, heat shock protein B1, and inflammation.

ABSTRACT

Acute lung injury (ALI) is a life-threatening condition characterized by respiratory failure. Rosuvastatin (RSV) is an antihypercholesterolemic agent with antioxidant properties. The current study aimed to investigate RSV novel therapeutic impact on ALI with emphasis on oxidative stress, inflammation, and heat shock protein B1 (HSPB1). Male albino rats (N = 30) were divided into five groups. Normal control (NC) group rats received normal saline 2 mL/kg P.O daily. Lipopolysaccharides (LPS) group rats received LPS (3 mg/kg intraperitoneally once). RSV group rats received RSV (2 mg/kg P.O daily). LPS + RSV group rats received RSV as in group 3 and on the 7th day rats received LPS as group 2. LPS + Dexamethasone (DX) rats received DX (2 mg/kg P.O, daily for one week) and on the 7th day rats received LPS as group 2. At the end of experiment (one week), lung tissue was used to determine HSPB1, high mobility group box 1 (HMGB1) using ELISA. IL-6, nuclear factor-2 (Nrf2), haem Oxygenase-1 (HO-1) protein levels were assessed using immunohistochemistry. GSH, catalase, MDA, NO, albumin and urea are assessed by colorimetry. The results revealed that RSV treatment resolved histopathological changes in lung tissue induced by LPS. Compared to LPS group, LPS + RSV group showed significant decrease in urea, NO, MDA, HMGB1, IL-6 and HO-1 level compared to LPS-treated rats. Conversely, RSV treatment significantly increased HSPB1, Nrf2, albumin, GSH, and CAT levels compared to LPS rats. RSV is effective for amelioration of ALI and thus can be used as adjuvant therapy for ALI.