Eun Soo Lee1, Hong Min Kim1, Jeong Suk Kang2, Eun Young Lee2, Dhananjay Yadav1, Mi-Hye Kwon1, You Mi Kim1, Hyeon Soo Kim3, Choon Hee Chung1. 1. Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do 220-701, Republic of Korea. 2. Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan 330-721, Republic of Korea. 3. Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Republic of Korea.
Abstract
BACKGROUND: Hyperglycemia-induced endoplasmic reticulum (ER) stress and oxidative stress could be causes of renal fibrosis in diabetes. Oleanolic acid (OA) naturally occurs in fruits and vegetables. It has anti-inflammatory, antihyperlipidemic and antioxidant effects. N-acetylcysteine (NAC) is a precursor of glutathione, which has a strong antioxidant effect in the body. In this study, we investigated the therapeutic effects of OA and NAC in diabetic nephropathy (DN). METHODS: Otsuka Long-Evans Tokushima Fatty rats were treated with OA (100 mg/kg/day) or NAC (300 mg/kg/day) for 20 weeks by oral gavage. RESULTS: The OA or NAC administration increased blood insulin secretion and superoxide dismutase levels, and decreased triglycerides and urinary albumin/creatinine levels. In the kidney, the damaged renal structure recovered with OA or NAC administration, through an increase in nephrin and endothelial selective adhesion molecules and a decrease in transforming growth factor-β/p-smad2/3 and ER stress. Reactive oxygen species and ER stress were increased by high glucose and ER stress inducers in cultured mesangial cells, and these levels recovered with OA (5.0 μM) or NAC (2.5 mM) treatment. CONCLUSION: The findings in this study suggest that OA and NAC have therapeutic effects for DN through an antioxidant effect and ER stress reduction.
BACKGROUND:Hyperglycemia-induced endoplasmic reticulum (ER) stress and oxidative stress could be causes of renal fibrosis in diabetes. Oleanolic acid (OA) naturally occurs in fruits and vegetables. It has anti-inflammatory, antihyperlipidemic and antioxidant effects. N-acetylcysteine (NAC) is a precursor of glutathione, which has a strong antioxidant effect in the body. In this study, we investigated the therapeutic effects of OA and NAC in diabetic nephropathy (DN). METHODS: Otsuka Long-Evans Tokushima Fatty rats were treated with OA (100 mg/kg/day) or NAC (300 mg/kg/day) for 20 weeks by oral gavage. RESULTS: The OA or NAC administration increased blood insulin secretion and superoxide dismutase levels, and decreased triglycerides and urinary albumin/creatinine levels. In the kidney, the damaged renal structure recovered with OA or NAC administration, through an increase in nephrin and endothelial selective adhesion molecules and a decrease in transforming growth factor-β/p-smad2/3 and ER stress. Reactive oxygen species and ER stress were increased by high glucose and ER stress inducers in cultured mesangial cells, and these levels recovered with OA (5.0 μM) or NAC (2.5 mM) treatment. CONCLUSION: The findings in this study suggest that OA and NAC have therapeutic effects for DN through an antioxidant effect and ER stress reduction.