• Journal of Nutrition and Health
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• v.42 no.8
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• pp.673-681
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• 2009

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-${\kappa}B$ activation was indirectly demonstrated by pI${\kappa}B$-${\alpna}$ and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-${\kappa}B$ activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-$1{\beta}$ and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

• Molecules and Cells
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• v.42 no.9
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• pp.672-685
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• 2019

Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygen-glucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation.

• Herbal Formula Science
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• v.29 no.2
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• pp.71-80
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• 2021

Objectives : This study investigated cellular-protective effects of Nardotidis seu Sulculii Concha water extract (NSCE) against oxidative stress induced by arachidonic acid (AA)+iron or tert-butylhydroperoxide (tBHP). Methods : In vitro, MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of AMP-activated kinase (AMPK) signaling pathway and autophagy related proteins. In vivo, mice were orally administrated with the aqueous extract of NSCE of 500 mg/kg for 3 days, and then injected with CCl₄ 0.5 mg/kg body weight to induce acute damage. The level of liver damage was measured by serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) analysis. Results : Treatment with NSCE inhibited cell death induced by AA+iron and tBHP. NSCE induced the phosphorylation of AMPK, and this compound also induced the phosphorylation of LKB1, an upstream kinase of AMPK, and Acetyl-CoA carboxylase (ACC), a primary downstream target of AMPK. NSCE increased the protein levels of autophagic markers (LC3II and beclin-1) and decreased the phosphorylation of mammalian target of rapamycin (mTOR) and simultaneously increased the phosphorylation of unc-51-like kinase-1 (ULK-1) in time-dependent manner. Conclusions : NSCE has the ability 1) to protect cells against oxidative stress induced by AA+iron or tBHP. NSCE 2) to activate AMP-activated protein kinase (AMPK), and 3) to regulate autophagy, an important regulator in cell survival.

• Journal of Life Science
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• v.20 no.2
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• pp.161-168
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• 2010

White-skinned sweet potato (Ipomoea batatas L.) has been traditionally used for diabetes treatment and management in many countries. In this experiment, methanol extract of white-skinned sweet potato (WSPMe) at a dose of 100 or 200 mg/kg body weight was tested to evaluate its effect on renal damage in streptozotocin (STZ)-induced diabetic rats. Its efficacy was compared with that of insulin secretogogue, glimepiride ($50\;{\mu}g/kg$ body weight). Experimental diabetes was induced by a single dose of STZ (45 mg/kg, i.p.) injection. The WSPMe and glimepiride were administered orally for 14 days and the effects on glucose, renal markers including blood urea nitrogen (BUN), creatinine and lactate dehydrogenase (LDH), lipid peroxide (LPO) level, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathion-S-transferase (GST) activities in kidney were studied. An increase in BUN, creatinine, LDH, glucose, LPO levels and decrease in SOD, CAT, GPx and GST features were observed in diabetic control rats. Administration of WSPMe at a dose of 200 mg/kg body weight caused a significant improvement in blood glucose, LPO level, renal markers, lipid peroxidation markers and increased antioxidant levels in diabetic kidney. In conclusion, the WSPMe was found to be effective in reducing oxidative stress, thus confirming the ethnopharmacological use of I. batatas L. in protecting diabetes and its complications.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5849-5855
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• 2012

Objective: The purpose of this study was to determine pretreatment effects of moderate-term endurance training before the various dosages (10 and $20{_{mg.kg}}^{-1}$) of DOX on a heat shock protein ($HSP_{70kda}$) and cardiotoxicity in heart tissue. Methods: Forty-eight male rats were randomly assigned to nontraining (NT) and training (T) groups and three subgroups; $DOX{_{10mg.kg}}^{-1}$ and $DOX{_{20mg.kg}}^{-1}$ and saline treatment. The training program included treadmill running between 25-39 min/day and 15-17 m/min, 5 days/wk for 3 wk. Result: DOX administration, in particularly with $20{_{mg.kg}}^{-1}$, caused up-regulation of oxidants and cardiac damage (MDA, CK, CPK-MB and CK/CPK-MB) and down-regulation of cardioprotection ($HSP_{70}$, SOD) markers, as compared to NT+saline group. Pretreatment effect of treadmill running endurance exercise in the presence of DOX with $10{_{mg.kg}}^{-1}$ caused a significant increase in $HSP_{70}$, SOD and a significant decrease in MDA and insignificant decrease in CK, CPK-MB and CK/CPK-MB, in comparison $T+DOX_{10}$ with $NT+DOX_{10}$ group. However, there was no significant difference between $T+DOX{_{10mg.kg}}^{-1}$ and $T+DOX{_{20mg.kg}}^{-1}$ in the aforesaid markers. Conclusion: Dox-induced cardiotoxicity is related to oxidative stress. Our study suggests that pretreatment with endurance exercise may be considered as a potentially useful strategy to improve myocardial tolerance against single dose DOX-induced oxidative damage.

• Journal of Life Science
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• v.19 no.4
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• pp.543-548
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• 2009

Treatment for breast cancer produces side effects that diminish functional capacity and quality of life (QOL) among survivors. Tai Chi is a moderate form of exercise that may improve functional capacity, physical activity and oxidative stress. The purpose of this study was to evaluate the effects of regular Tai Chi exercise on malondialdehyde (MDA), SOD and physical fitness (muscle strength, flexibility, flexion, extension, adduction, and abduction). Forty obese women were recruited from a public health center and divided into control (CON: n=20) and trained (EXP: n=20) groups. The Tai Chi exercise group participated in a 12-week (4 times/week) training program. Data were analyzed with T-test. MDA, SOD and physical fitness (muscle strength, flexibility, flexion, extension, adduction, and abduction) were evaluated before and after the Tai Chi program in both groups. There were significant improvements in shoulder flexibility, flexion, extension, abduction, and adduction. However, there was no improvement in muscle strength. There were also significant improvements in MDA and SOD. Based on these results, Tai Chi exercise has been shown to stimulate endogenous antioxidant enzymes and reduce oxidative damage markers. and also be effective in improving physical fitness and QOL. Further study is needed in this area.

• Korean Journal of Food Science and Technology
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• v.44 no.1
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• pp.82-88
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• 2012

Chrysanthemum indicum L. (Asteraceae) is a traditional herbal medicine that has been used for the treatment of inflammation, hypertension, and respiratory diseases due to its strong antagonistic activity against inflammatory cytokines. The effects of Chrysanthemum indicum L. Extract (CIE) for increasing cell growth, alkaline phosphatase (ALP) activity, and collagen content were totally inhibited, suggesting that the effect of CIE might be partly involved with estrogen activity. Furthermore, the protective effects of CIE on the response of osteoblasts to oxidative stress were evaluated. Osteoblastic MC3T3-E1 cells were incubated with hydrogen peroxide and/or CIE, and markers of osteoblast function and oxidative damage were examined. CIE significantly increased cell survival, ALP activity, and calcium deposition, and decreased the production of Reactive Oxygen Species (ROS) and Tumor Necrosis Factor-${\alpha}$ (TNF-${\alpha}$) in osteoblasts. Taken together, these results indicate that the enhancement of osteoblast function by CIE may prevent osteoporosis and inflammatory bone diseases.

• Molecules and Cells
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• v.41 no.5
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• pp.401-412
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• 2018

Oxymatrine (OMT) often used in treatment for chronic hepatitis B virus infection in clinic. However, OMT-induced liver injury has been reported. In this study, we aim to investigate the possible mechanism of OMT-induced hepatotoxicity in human normal liver cells (L02). Exposed cells to OMT, the cell viability was decreased and apoptosis rate increased, the intracellular markers of oxidative stress were changed. Simultaneously, OMT altered apoptotic related proteins levels, including Bcl-2, Bax and pro-caspase-8/-9/-3. In addition, OMT enhanced the protein levels of endoplasmic reticulum (ER) stress makers (GRP78/Bip, CHOP, and cleaved-Caspase-4) and phosphorylation of c-Jun N-terminal kinase (p-JNK), as well as the mRNA levels of GRP78/Bip, CHOP, caspase-4, and ER stress sensors (IREI, ATF6, and PERK). Pre-treatment with Z-VAD-fmk, JNK inhibitor SP600125 and N-acetyl-l-cysteine (NAC), a ROS scavenger, partly improved the survival rates and restored OMT-induced cellular damage, and reduced caspase-3 cleavage. SP600125 or NAC reduced OMT-induced p-JNK and NAC significantly lowered caspase-4. Furthermore, 4-PBA, the ER stress inhibitor, weakened inhibitory effect of OMT on cells, on the contrary, TM worsen. 4-PBA also reduced the levels of p-JNK and cleaved-caspase-3 proteins. Therefore, OMT-induced injury in L02 cells was related to ROS mediated p-JNK and ER stress induction. Antioxidant, by inhibition of p-JNK or ER stress, may be a feasible method to alleviate OMT-induced liver injury.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.1
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• pp.1-13
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• 2022

Kidney disease is becoming a global public health issue. Acute kidney injury (AKI) and chronic kidney disease (CKD) have serious adverse health outcomes. However, there is no effective therapy to treat these diseases. Lactoferrin (LF), a multi-functional glycoprotein, is protective against various pathophysiological conditions in various disease models. LF shows protective effects against AKI and CKD. LF reduces markers related to inflammation, oxidative stress, apoptosis, and kidney fibrosis, and induces autophagy and mitochondrial biogenesis in the kidney. Although there are no clinical trials of LF to treat kidney disease, several clinical trials and studies on LF-based drug development are ongoing. In this review, we discussed the possible kidney protective mechanisms of LF, as well as the pharmacological and therapeutic advances. The evidence suggests that LF may become a potent pharmacological agent to treat kidney diseases.

• Journal of Plant Biotechnology
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• v.46 no.4
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• pp.331-337
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• 2019

Digitaria exilis L. is an under-utilized crop with high nutritional and medicinal values. It thrives in and is well-adapted to arid areas with low soil nutrients. Using biochemical markers, this study investigates the mechanisms by which D. exilis responds to osmotic stress. Three accessions Dinat Iburua (DIN), Jakah Iburua (JAK) and Jiw Iburua (JIW) were collected from National Cereal Research Institute, Niger State. Two accessions, NG/11/JD/061 and NG/11/JD/062 were also collected from National Centre for Genetic Resources and Biotechnology, Ibadan. Murashige and Skoog medium of approximately 1.2 L was supplemented with polyethylene glycol 6000 to create osmotic pressures of -9.29, -13.93, -20.13, -26.32, -32.51, and 0 MPa (control). Sterilized seeds were inoculated in the medium and placed in the growth room for 4 weeks. Proline accumulation was significantly high in all JAK plants under osmotic stress. Proline and ascorbate peroxidase (p<0.05) activities were directly correlated, thus reinforcing the survivability of JAK during stress. Catalase (CAT) activity was also significantly induced in JAK under osmotic stress, which synergistically improved its tolerability. As a result, >50% of OH-, H₂O₂, and NO radicals were scavenged. However, other accessions including DIN, NG061, NG062, and JIW showed variations in their responses to different levels of osmotic stress, although not significant. Therefore, JAK possesses a well-equipped free radical quenching system that is protected by the accumulation of the osmolyte proline; therefore, accession JAK is considered osmotolerant. CAT and superoxide dismutase activities were osmostabilized against oxidative stress by proline.