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Protective effects of regular exercise and Korea red ginseng against high-fat diet-increased renal injury in ᴅ-galactose-induced aging rats
- Alternative Title
- Chan-Sik Kim
- Author(s)
- Kim, Chan Sik
- Alternative Author(s)
- Chan-Sik Kim
- Advisor
- 이수환, 정이숙
- Department
- 일반대학원 의학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2014-02
- Language
- eng
- Keyword
- Age-related renal injury; ᴅ-Galactose; Exercise; High-fat diet; Korean red ginseng; Oxidative stress
- Alternative Abstract
- A decline in renal function is seen commonly in aging. Aging further increase oxidative stress in the kidney and are associated with reduced renal function. Aging is progressive accumulation of oxidative agents. Advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs) formation has been implicated in the aging process. Obesity induced by a high-fat diet (HFD) may reduce renal function. However, the impact of obese on the age-related renal disease is not well understood. Exercise reduces oxidative stress. Korean red ginseng (KRG) has been reported to ameliorate oxidative tissue injury and has an anti-aging effect. The purpose of this study was to investigate whether HFD would accelerate ᴅ-galactose (GAL)-induced renal injury and to examine the preventive effects of a regular exercise and KRG on GAL/HFD -induced renal injury. In the first experiment, age-related renal injury was induced by an administration with GAL (100 mg/kg, i.p.) in the absence or presence of high-fat diet (60% kcal as fat) for 9 weeks. The exercise group was trained on a motorized treadmill for 60 min/day, 5 times/week over the same period. In the second experiment, in vitro inhibitory effect of KRG on AGEs-cross-linking was examined by enzyme-linked immunosorbent assay (ELISA), and KRG (200 mg/kg/day) was given to GAL plus HFD-induced aging rats for 9 weeks. Immunohistochemical staining for 8-OHdG (a specific marker of oxidative DNA damage) and CMLs (a marker of both glycation and lipoxidation reactions) revealed that GAL-treated rats fed a HFD showed aggravated renal injury associated with more pronounced renal AGEs/ALEs formation and oxidative DNA damage. In TUNEL assay, the numbers of TUNEL-positive cell in the GAL/HFD group were significantly higher than the GAL group. The expression of activated caspase-3 protein and Bax/Bcl-2 ratio also were significantly increased in the GAL/HFD group than that in the GAL group. Moreover, imuunohistochemical staining for synaptopodin and WT-1, well-known podocyte markers, revealed that HFD aggravates the loss of podocytes in renal glomeruli. However, the regular exercise restored all these renal changes in HFD plus GAL-treated rats. KRG inhibited AGEs and collagen cross-link at ten-fold less concentration (IC50=55.65 μg/ml) than aminoguanidine (IC50=563.54 μg/ml), a well-known glycation inhibitor. When rats were fed with a HFD for 9 weeks in GAL-induced aging rats, renal AGEs accumulation, extracellular high mobility group box 1 protein (HMGB1), a signal of tissue damage) and receptor for AGE (RAGE) were extensively expressed in renal tissues of the GAL/HFD group than that in the GAL group. HMGB1 was clearly translocated from the nucleus to the cytoplasm in renal tubular epithelial cells. However, treatment of HFD plus GAL-induced aging rats with KRG restored all these renal changes. In summary, when rats were fed with a HFD for 9 weeks in GAL-induced aging rats, oxidative DNA damage, protein glycations, renal cell apoptosis and cytoplasmic translocation of HMGB1 were caused in renal glomerular cells and tubular epithelial cells. However, the regular exercise and KRG treatment restored all these renal changes in GAL/HFD-treated rats. Therefore, this study suggested that long-term HFD may accelerate the deposition of AGEs/ALEs and oxidative renal injury in GAL-treated rats. This HFD-increased renal injury in GAL-induced aging rats could be suppressed by regular exercise and KRG through the repression of oxidative injury.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Medicine > 3. Theses(Master)
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