Negative air ions alleviate nicotine-induced renal damage of spontaneously hypertensive rats via inhibiting oxidative stress and TGF-β/Smad pathway

Background: Nicotine can lead to renal damage in hypertension patients. Negative air ions (NAIs) is a natural antioxidant. However, rare research focus on the effect of NAIs on nicotine aggravated oxidative damage and hypertensive kidney damage. Methods: We used a spontaneously hypertensive rat (SHR) model to investigate the molecular mechanisms for nicotine-exacerbated renal damage and the intervention effect of NAIs. 8-week-old male rats were injected with nicotine or nicotine+ 6 h/d 4.5 x 104 to 5 x 104 NAIs/cm3 for 1 month or 3 months, and continuous observation of systolic blood pressure (SBP). Urine and blood were collected for test kidney injury, inflammation and oxidative stress levels, and renal tissues were harvested for pathology analysis and further molecular assays using RT-qPCR, Western blot, and immunohistochemistry. Results: Our results showed that nicotine exacerbated SBP and renal damage, and elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in SHR. After 3 months of 1.5 mg/kg nicotine exposure, serum levels of urea nitrogen (BUN) and transforming growth factor beta 1 (TGF-beta 1) in SHR increased by 1.3 times and 16.3 times, respectively. In addition, oxidative damage was significantly increased along with the activation of TGF-beta/Smad pathway and promotion of epithelial mesenchymal transition (EMT), key factors reflected in the higher expression of NADPH oxidase (NOX2), alpha-SMA and N-cadherin proteins and increased mRNA levels of fibronectin-1 (FN1) and Twist. After NAIs intervention, levels of BUN, urinary creatinine ratio, TGF-beta 1, endothelin 1 (ET-1) and malondialdehyde (MDA) were decreased close to SHR without nicotine exposure, and we also observed oxidative damage was significantly decreased and TGF-beta/Smad pathway and EMT related factors were significantly down-regulated. Conclusions: NAIs can attenuated nicotine-exacerbated hypertensive renal damage and fibrosis process through inhibiting oxidative stress and TGF-beta/Smad pathway. We suggest that NAIs intervention could be proposed a new approach to adjuvant therapy of chronic kidney disease in smokers with hypertension.