• Journal of Ginseng Research
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• 제37권4호
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• pp.379-388
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• 2013

Diabetic nephropathy is one of the serious complications in patients with either type 1 or 2 diabetes mellitus but current treatments remain unsatisfactory. Results of clinical research studies demonstrate that Panax ginseng can help adjust blood pressure and reduce blood sugar and may be advantageous in the treatment of tuberculosis and kidney damage in people with diabetes. The heat-processing method to strengthen the efficacy of P. ginseng has been well-defined based on a long history of ethnopharmacological evidence. The protective effects of P. ginseng on pathological conditions and renal damage associated with diabetic nephropathy in the animal models were markedly improved by heat-processing. The concentrations of less-polar ginsenosides (20(S)-Rg3, 20(R)-Rg3, Rg5, and Rk1) and maltol in P. ginseng were significantly increased in a heat-processing temperature-dependent manner. Based on researches in animal models of diabetes, ginsenoside 20(S)-Rg3 and maltol were evaluated to have therapeutic potential against diabetic renal damage. These effects were achieved through the inhibition of inflammatory pathway activated by oxidative stress and advanced glycation endproducts. These findings indicate that ginsenoside 20(S)-Rg3 and maltol are important bioactive constituents of heat-processed ginseng in the control of pathological conditions associated with diabetic nephropathy.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.109-121
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• 2023

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6877-6882
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• 2015

Background: Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer. We investigated the effect of selenium (Se) with high dose vitamin E (VE) administration to prevent CDDP-induced nephrotoxicity in rats. Materials and Methods: In this study, 40 female Wistar rats were randomly divided into five equal groups. The first group, which served as the control, was administered physiological saline (2.5 cc/day, 5 days) intraperitoneally (IP), while group A was administered cisplatin (6 mg/kg BW/ single dose) plus physiological saline IP. Groups B, C, D received IP five doses of Se (1.5 mg/kg BW), and a high dose of VE (1000 mg/kg BW) (Se-VE) in combination before, simultaneously, and after CDDP, respectively. The rats were sacrificed five days after CDDP administration. Plasma malondialdehide (MDA), glutathione peroxidase (GSH-Px), reduced glutathione (GSH), catalase, urea, creatinine levels, renal histopathological changes were measured. Results: The histopathological injury score, plasma levels of MDA, urea, creatinine were found to increase in group A compared to the control (p<0.05), while plasma levels of GSH-Px, GSH and catalase decreased (p<0.05). In contrast, plasma levels of MDA decreased (p<0.05) in groups B, C, D, which were treated with Se- VE, whereas levels of GSH-Px, GSH were found to increase only for group D (p<0.05). Plasma urea, creatinine levels improved in the treatment groups compared to group A (p<0.001). Histopathological changes caused by CDDP were also significantly improved after Se-VE treatment (p<0.05). Conclusions: Oxidative stress increases with CDDP-induced nephrotoxicity in rats. Se-VE supplementation might thus play a role in the prevention of CDDP-induced nephrotoxicity in patients.

• 한국어병학회지
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• 제32권2호
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• pp.113-121
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• 2019

Effects on glutathione-related antioxidant parameters were examined after a chronic exposure of olive flounder, Paralichthys olivaceus to dietary 4-tert-octylphenol (4-tert-OP). Fish were fed diets containing 4-tert-OP at 0, 1, 5 and 10 mg/kg diet for 6 weeks. Antioxidant parameters examined were reduced glutathione (GSH) contents and enzyme activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPx) in tissue homogenates of the liver, kidney and gill. It was observed that all parameters examined increased although there were some differences in dose responses and temporal patterns in the increase. GSH contents increased after exposure to 4-tert-OP in the three organs examined. However, the GSH increase was evident only after 4 weeks in the liver whereas it was elevated after 2 weeks in the kidney and gill. GR activity exhibited a significant increase in response to 4-tert-OP at 1 mg/kg in all three organs, however, its activity returned to control levels when exposed to 5 and 10 mg/kg. Hepatic GST activity showed an earlier increase at week 2 in contrast to the kidney and gill where they increased after 4 weeks of 4-tert-OP exposure. Temporal patterns in GPx activity changes to 4-tert-OP exposure were dissimilar among the organs: hepatic activity increased from week 2 through week 6; renal activity increased transiently at week 2; gill levels were higher through weeks 4 - 6. The results suggest that elevation of several GSH-related antioxidant parameters can be considered as evaluation criteria for 4-tert-OP-induced oxidative stress in a fish.

• 대한한의학회지
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• 제28권3호통권71호
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• pp.57-69
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• 2007

Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications have shown that oxidative stress might play a major role. Therefore, many methods have been tried to regulate free oxygen radicals for treating diabetes and its complications. Ojung-hwan, composed of five crude herbs, has been considered effective for treating symptoms of aging. In male ob/ob mouse of severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activities and mechanisms of Ojung-hwan were examined. Methods : Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. The effects of Ojung-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical (${\cdot}\;O{_2}{^-}$), MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Results : Ojung-hwan lowered the levels of serum glucose and insulin in a dose-dependent manner. Total cholesterol, triglyceride and free fatty acid levels decreased, while the HDL-cholesterol level increased, in Ojung-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities increased in the ob/ob mice, whereas they were inhibited in the Ojung-hwan treated groups. Ojung-hwan inhibited the generation of ${\cdot}\;O{_2}{^-}$ in the kidney. Finally, MDA+HAE levels increased and GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Ojung-hwan treated groups. Conclusions : Ojung-hwan showed antidiabetic and antihyperlipidemic activities by regulating theactivities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• The Korean Journal of Physiology and Pharmacology
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• 제8권3호
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• pp.117-127
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• 2004

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

• Nutrition Research and Practice
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• 제8권2호
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• pp.220-226
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• 2014

BACKGROUND/OBJECTIVES: Arsenic, which causes human carcinogenicity, is ubiquitous in the environment. This study was designed to evaluate modulation of arsenic induced cancer by resveratrol, a phytoalexin found in vegetal dietary sources that has antioxidant and chemopreventive properties, in arsenic trioxide ($As_2O_3$)-induced Male Wistar rats. MATERIALS/METHODS: Adult rats received 3 mg/kg $As_2O_3$ (intravenous injection, iv.) on alternate days for 4 days. Resveratrol (8 mg/kg) was administered (iv.) 1 h before $As_2O_3$ treatment. The plasma and homogenization enzymes associated with oxidative stress of rat kidneys were measured, the kidneys were examined histologically and trace element contents were assessed. RESULTS: Rats treated with $As_2O_3$ had significantly higher oxidative stress and kidney arsenic accumulation; however, pretreatment with resveratrol reversed these changes. In addition, prior to treatment with resveratrol resulted in lower blood urea nitrogen, creatinine and insignificant renal tubular epithelial cell necrosis. Furthermore, the presence of resveratrol preserved the selenium content ($0.805{\pm}0.059{\mu}g/g$) of kidneys in rats treated with $As_2O_3$. However, resveratrol had no effect on zinc level in the kidney relative to $As_2O_3$-treated groups. CONCLUSIONS: Our data show that supplementation with resveratrol alleviated nephrotoxicity by improving antioxidant capacity and arsenic efflux. These findings suggest that resveratrol has the potential to protect against kidney damage in populations exposed to arsenic.

• 대한한방내과학회지
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• 제35권1호
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• pp.92-105
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• 2014

목 적 : 본 연구는 청허열약(淸虛熱藥)으로서 폐(肺), 간(肝), 신경(腎經)에 귀경(歸經)하여 양혈제증(凉血除蒸), 청폐강화(淸肺降火)의 효능으로 음허조열(陰虛潮熱), 골증도한(骨蒸盜汗), 폐열해수(骨蒸盜汗), 객혈(喀血), 육혈(衄血), 내열소갈(內熱消渴) 등의 치료에 상용되는 지골피(地骨皮)에 대해, 산화적 스트레스를 유발하여 신 독성을 일으키는 것으로 알려진 cisplatin을 투여한 Wistar rats에서의 신기능 손상 방지 효능을 관찰하고, 산화적 스트레스 및 그로 인한 염증반응 관련 전사인자와 효소들에 대한 억제효과와 항산화제를 촉진하는 효능을 확인하였다. 방 법 : Cisplatin으로 급성신부전증이 유도된 Wistar rats에서 地骨皮의 복용으로 인한 혈중 BUN 수치 변화를 관찰함으로써 신기능 보호효과를 확인하였다. Cisplatin으로 인한 신 손상의 주요 기전으로 알려진 산화적 스트레스에 대한 억제 효과를 확인하기 위하여 신 조직에서의 ROS, TBARS 수치를 관찰하고, ROS를 생성시키는 NADPH oxidase의 subunits인 NOX-4, $p47^{phox}$, $p22^{phox}$와 산화적 스트레스로 유도되는 염증반응과 관련한 NF-${\kappa}B$의 활성 및 COX-2, iNOS의 단백질 발현정도를 Western blotting을 통해 확인하였다. 또한 주요 항산화제인 glutathione의 환원형과 산화형 수치를 각각 확인하고 그 비율을 조사하였으며, 또 다른 항산화제인 SOD, catalase의 발현정도를 Western blotting을 통해 확인함으로써 地骨皮의 항산화제 촉진 효능을 관찰하였다. 결 과 : 지골피(地骨皮)는 cisplatin으로 유도된 급성신부전증 모델에서 증가한 혈중 BUN 수치를 감소시켜 신기능 손상을 유효하게 방지하였다. 또한 cisplatin 투여는 Wistar rats에서 산화적 스트레스 및 그로 인한 염증반응 관련 전사인자와 효소들의 발현을 항진시켜 cisplatin의 신 독성 기전이 산화적 스트레스로 초래됨을 확인할 수 있었으며, 지골피(地骨皮) 투여군의 경우 신조직 ROS, TBARS, NADPH oxidase를 유의하게 감소시켰고 NF-${\kappa}B$의 활성과 COX-2, iNOS 발현 또한 억제하는 것을 관찰하였다. 나아가 주요 항산화제로 알려진 GSH, SOD 및 catalase에 대한 지골피(地骨皮)의 촉진효과를 확인하였다. 결 론 : 이상의 결과로 지골피(地骨皮)는 신기능 손상을 방지하고, 항산화제 활성을 촉진시켜 산화적 스트레스와 염증반응을 효과적으로 저해함으로써 cisplatin으로 유발되는 급성신부전증의 치료 및 예방에 활용될 수 있음이 시사되었다.

• Korean Journal of Acupuncture
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• 제36권1호
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• pp.63-73
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• 2019

Objectives : This study was designed to investigate the effects of Alismatis Rhizoma (AR) pharmacopuncture at BL23 on acute renal failure induced by cisplatin. Methods : The Sprague-Dawley rats were divided into Normal group (no injection of cisplatin and no treatment), Control group (cisplatin injection without treatment), Acu group (needling at BL23 after cisplatin injection), AR-PA1 group (treated with $0.3571mg/kg/20{\mu}l$ of AR pharmacopuncture at BL23 after cisplatin injection), and AR-PA2 group (treated with $1.7855mg/kg/20{\mu}l$ of AR pharmacopuncture at BL23 after cisplatin injection). Each treatment was given once daily for 8 days. Changes in body weight, kidney weight, tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), Cu-Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GPx), serum blood urea nitrogen (serum BUN), and serum creatinine were observed. Results : Body weight was significantly increased in AR-PA1 on $4^{th}$ and $6^{th}$ days and AR-PA2 on $2^{nd}$ day. $TNF-{\alpha}$ was significantly decreased in Acu, AR-PA1 and AR-PA2 groups. Cu-Zn SOD was significantly increased in AR-PA2 group. GPx was significantly increased in AR-PA1 and AR-PA2 groups. But kidney weight, IL-6, serum BUN and serum creatinine were not significantly changed in any groups compared to control group. Conclusions : In acute renal failure induced by cisplatin, AR pharmacopuncture has a mitigating effect on the inflammatory reaction related to the increase of $TNF-{\alpha}$ in the kidney tissue and a protective effect on the oxidative stress of the kidney tissue. However it is unlikely to restore the glomerular function or inhibit the renal swelling.

• 한국식품영양과학회지
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• 제44권6호
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• pp.809-815
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• 2015

본 연구에서는 국내산 법제 하수오 메탄올 추출물로부터 생리활성물질을 확인하였고, 추출물의 라디칼 소거능과 LLC-$PK_1$ cell을 이용한 산화적 스트레스 개선 효과를 살펴보았다. HPLC 분석 결과 4종의 생리활성물질인 2,3,5,4'-tetrahydroxystilbene 2-O-${\beta}$-D-glucoside, emodin, chrysophanol 및 rhein을 확인하였다. 특히 주요 화합물인 2,3, 5,4'-tetrahydroxystilbene 2-O-${\beta}$-D-glucoside는 115.02 mg/kg이었다. 법제 하수오 추출물의 DPPH, ABTS, hydroxyl 라디칼 소거능은 농도 의존적으로 증가하였다. 추출물의 $50{\mu}g/mL$ 처리 시 DPPH 라디칼 소거능은 48.4%, ABTS 라디칼 소거능은 57.9% 및 hydroxyl 라디칼 소거능은 81.2%로 나타내었다. 한편 LLC-$PK_1$ cell에서 각각의 NO, $O_2{^-}$, 및 $ONOO^-$ 생성물질인 pyrogallol, sodium nitroprusside(SNP) 및 morpholinosydnonimine(SIN-1) 처리에 의해 유도된 산화적 스트레스 상에서 세포 생존율은 감소하였다. 그러나 법제 하수오 메탄올 추출물은 농도 의존적으로 세포 독성을 저해하였다. 추출물의 $50{\mu}g/mL$ 처리 시 세포 생존율은 각각 82.1%(pyrogallol), 89.1%(SNP) 및 77.6%(SIN-1)였다.