Oleanolic acid attenuates renal fibrosis in mice with unilateral ureteral obstruction via facilitating nuclear translocation of Nrf2
1 Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seoul 137-701, Republic of Korea
2 Division of Nephrology, The Catholic University of Korea Yeouido St. Mary’s Hospital, 10, 63-ro, Yeongdeungpo-gu, Seoul 150-713, Republic of Korea
3 Division of Nephrology, The Catholic University of Korea Incheon St. Mary’s Hospital, 56, Dongsu-ro, Bupyeong-gu, Incheon 403-720, Republic of Korea
4 Division of Nephrology, The Catholic University of Korea Seoul St. Mary’s Hospital, 222, Banpo-daero, Seoul 137-701, Republic of Korea
5 Division of Nephrology, Korea University Guro Hospital, 148, Gurodong-ro, Guro-gu, Seoul 152-703, Republic of Korea
Nutrition & Metabolism 2014, 11:2 doi:10.1186/1743-7075-11-2Published: 6 January 2014
Renal interstitial fibrosis is a common final pathological process in the progression of kidney disease. This is primarily due to oxidative stress, which contributes to renal inflammation and fibrosis. Nuclear factor-erythroid-2-related factor 2 (Nrf2) is known to coordinate induction of genes that encode antioxidant enzymes. We investigated the effects of oleanolic acid, a known Nrf2 activator, on oxidative stress-induced renal inflammation and fibrosis.
One day before unilateral ureteral obstruction (UUO) performed in C57BL/6 mice, oleanolic acid treatment was initiated and was continued until 3 and 7 days after UUO. Renal inflammation and fibrosis, markers of oxidative stress, and changes in Nrf2 expression were subsequently evaluated.
In the obstructed kidneys of UUO mice, oleanolic acid significantly attenuated UUO-induced collagen deposition and fibrosis on day 7. Additionally, significantly less inflammatory cell infiltration, a lower ratio of Bax to Bcl-2 expression, and fewer apoptotic cells on TUNEL staining were observed in the obstructed kidneys of oleanolic acid-treated mice. Oleanolic acid increased the expression of nuclear Nrf2, heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and heat shock protein 70, and decreased lipid peroxidation in the obstructed kidney of UUO mice. There were no changes in the expression of total Nrf2 and Kelch-like ECH-associated protein 1, indicating that oleanolic acid enhanced nuclear translocation of Nrf2.
These results suggest that oleanolic acid may exert beneficial effects on renal fibrosis by increasing nuclear translocation of Nrf2 and subsequently reducing renal oxidative stress.