Cryptotanshinone Attenuates Oxidative Stress and Inflammation through the Regulation of Nrf-2 and NF-κB in Mice with Unilateral Ureteral Obstruction

Abstract

Oxidative stress and inflammatory responses are closely implicated in the progression of renal interstitial fibrosis, thereby leading to chronic kidney disease. Cryptotanshinone (CTS) is a natural compound involved in antioxidant and anti-inflammatory activities. We evaluated the effects of CTS on inflammation and oxidative stress in obstructed kidneys. Mice received gastric gavage of CTS from 7 days before unilateral ureteral obstruction operation to 1 week after surgery. Administration of CTS at 50 and 100 mg/kg/day significantly decreased collagen production, as shown by Masson staining. Immunohistochemistry staining and RT-PCR confirmed that CTS reduced extracellular matrix proteins, such as fibronectin and collagen-1, in the obstructed kidneys in a dose-dependent manner. Furthermore, immunohistochemistry staining indicated that CTS inhibited infiltration of the macrophage (CD68-positive) and lymphocyte (CD3-positive) cells, which were associated with the suppression of the nuclear factor-κB signalling activation. CTS increased superoxide dismutase, catalase and glutathione while decreased malondialdehyde production. More importantly, CTS activated Nrf-2 and HO-1 in the obstructed kidneys for 7 days. CTS could protect renal interstitial fibrosis by ameliorating inflammation and oxidative stress, which might be through the regulation of NF-κB and Nrf-2/HO-1 signalling pathways.