Impaired Nrf2-ARE pathway contributes to increased oxidative damage in kidney of spontaneously hypertensive rats: Effect of antioxidant (honey)

Methods: Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcription factor that regulates antioxidant response element (ARE)-coordinated genes and enzymes. This study examined the status of Nrf2 in kidney of spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY). The study also investigated the activities and mRNA expressions of antioxidant enzymes (AOEs), total antioxidant status (TAS) and malondialdehyde (MDA) in relation to Nrf2 in kidney of SHR and WKY. We also investigated the effects of antioxidant (honey) on systolic blood pressure (SBP), activities and mRNA expressions of AOEs and Nrf2. SHR and WKY were administered distilled water or honey by gavage once daily for 12 weeks. After sacrifice, the kidneys were excised and processed. Results: Control SHR had significantly (P<0.001) elevated SBP. The Nrf2 mRNA expression level was markedly (P<0.05) down-regulated in kidney of control SHR compared with control WKY. The mRNA glutathione-S-transferase (GST) expression level was significantly (P<0.01) reduced in kidney of control SHR. MDA was significantly (P<0.01) increased in kidney of control SHR. However, SHR showed significantly (P<0.01) increased activities of catalase (CAT) and GST. TAS was also appreciably (P<0.05) increased in control SHR. Honey significantly (P<0.01) reduced SBP and MDA levels in SHR. Besides, honey significantly (P<0.01) attenuated activities of CAT and GST whereas it moderately, but not significantly, up-regulated mRNA expression levels of Nrf2 and AOEs in kidney of SHR. Conclusions: The study shows that impaired Nrf2 function plays an important role in the insufficiency of kidney of SHR to counteract oxidative damage. Honey supplementation reduces SBP, MDA and attenuates the activities of AOEs in kidney of SHR. Investigation of protein expressions of Nrf2 and AOEs may reveal the mechanisms for increased activities of CAT and GST in kidney of SHR.