• The Korean Journal of Physiology and Pharmacology
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• 제7권1호
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• pp.39-45
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• 2003

Reactive oxygen species (ROS) have been suggested to be contributory factors in complications of diabetes mellitus. In the present study, we investigated the generation of superoxide, the lipid peroxide level measured as thiobarbituric acid reactive substances, the vasorelaxation of isolated thoracic aorta and the iNOS expression in kidney of streptozotocin induced diabetic rats. Sprague Dawley rats were divided into four groups: control, ascorbate (400 mg/kg rat weight daily in drinking water), diabetic (single dose of 50 mg of STZ/kg i.p.) and diabetic simultaneously fed with ascorbate for 12 wk. Rats in groups were studied at tri-weekly intervals (0 to 12 wk). Diabetic rats were evaluated periodically with changes of plasma glucose levels and body weight. The ascorbate supplimentation attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. In the present experimental condition, the ascorbate supplimentation had no significant effect on plasma glucose levels and changes in body weight of normal rate. The superoxide generation, formation of thiobarbituric acid reactive substance and iNOS expression in kidney were significantly increased in STZ-treated rats that were decreased by ascorbate supplimentation. The ascorbate supplimentation had no effect on vasorelaxation of isolated thoracic aorta. These results indicate that ascorbate supplimentation may exert an inhibitory effect on STZ-induced oxidative tissue damage through protection of pancreatic islet cells by scavanging reactive oxygen species. The ascorbate supplimentation may possibly attenuate the renal complication of diabetes mellitus.

• Toxicological Research
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• 제35권2호
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• pp.181-190
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• 2019

Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.

• 대한본초학회지
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• 제28권6호
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• pp.39-45
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• 2013

Objectives : This study was conduct to compare of histological changes on four target organs which related with diabetes in streptozotocin-induced diabetic rats. Methods : Diabetes was induced in male Sprague-Dawley rats by consecutive injection of streptozotocin (STZ) at different doses of 30, 40 and 50 mg/kg for 5 days. After 4 weeks, all rats were sacrificed, five different organs such as pancreas, liver, kidney, and lung were isolated and observed their histological changes by hematoxylin and eosin (H&E), Periodic acid-Schiff (PAS) and Masson's trichrome staining. The changes of body weight, blood glucose, and food and water intake were also measured. Results : The multiple administration of STZ was induced diabetes in rats with hyperglycemia, decrease of body weight, increase water and food intake, and histopathological changes of target organs, compared with those of normal rats in both dose-dependent and time-dependent manner. In histological analysis, pancreas was showed decrease of the islet numbers with beta-cell loss. Kidney showed morphological damage with glomerulus hypertrophy, and also lung was showed bronchial epithelial damage with inflammatory cells infiltration. In liver, the portal vein and hepatic artery could not observed, and showed inflammatory cell infiltration with liver fibrosis. Conclusions : These results suggest that the increase of the capacity of STZ, each of the more chronic disease, it can be seen that the damage was deep. Thus, evaluate the resulting drug appropriate depending on the purpose of the model is expected to be selected.

• Journal of Veterinary Science
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• 제21권6호
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• 대한이식학회지
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• 제31권4호
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• pp.200-206
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• 2017

Background: Risk factors for bone avascular necrosis (AVN), a common late complication after kidney transplantation (KT), are not well known. Methods: Patients that underwent living-donor KT at Asan Medical Center between January 2009 and July 2016 were included in this retrospective study to determine the incidence and risk factors for AVN after KT. Results: Among 1,570 patients that underwent living-donor KT, 33 (2.1%) developed AVN during a mean follow-up of 49.8±25.0 months. Additionally, AVN was diagnosed at a mean of 13.9±6.6 months after KT. The mean cumulative corticosteroid dose during the last follow-up in patients without AVN (9,108±3,400 mg) was higher than that that in patients with AVN (4,483±1,114 mg) until AVN development (P<0.01). More patients among those with AVN (n=4, 12.1%) underwent steroid pulse treatment because of biopsy-proven rejections during the first 6 months after KT than patients without AVN (n=68, 4.4%; P=0.04). Female (hazard ratio [HR], 2.29; P=0.04) and steroid pulse treatment during the first 6 months (HR, 2.31; P=0.02) were significant AVN risk factors as revealed by the Cox proportional multivariate analysis. However, no significant differences in rejection-free graft survival rates were observed between the two groups (P=0.67). Conclusions: Steroid pulse treatment within 6 months of KT and being female were independent risk factors for AVN development.

• Clinical and Experimental Reproductive Medicine
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• 제49권4호
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• pp.239-247
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• 2022

Objective: Asafoetida is a gum derived from Ferula assa-foetida, which is used in traditional Iranian medicine to treat some reproductive system disorders. The effects of asafoetida on ovarian tissue, expression of certain genes associated with polycystic ovary syndrome (PCOS), and levels of liver, kidney, and blood cell factors after treatment in a rat model were investigated. Methods: Thirty rats were divided into five groups: normal, polycystic, and treatment with three doses of asafoetida (12.5, 25, and 50 mg/kg for 3 weeks after PCOS induction). PCOS was induced by letrozole at a dose of 1 mg/kg administered orally for 3 weeks. Blood samples were taken, and the ovaries were removed and prepared for histomorphometric examination. Liver and kidney parameters were measured. The mRNA expression levels of luteinizing hormone receptor, CYP11A1, adenosine monophosphate-activated protein kinase, adiponectin, and adiponectin receptors 1 and 2 were also measured by real-time polymerase chain reaction. Results: The levels of liver, kidney, and blood parameters did not significantly differ between the treatment groups and the control group. At doses of 25 and 50 mg/kg, ovarian histopathology, especially the thicknesses of the theca and granulosa layers, was significantly improved relative to the PCOS group. The expression of target genes also improved in the 25 and 50 mg/kg treatment groups. Conclusion: Asafoetida can be used to treat PCOS as a complementary approach to conventional therapies. Asafoetida appears to act by regulating and activating metabolic and ovarian cycle enzymes.

• Clinical and Experimental Vaccine Research
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• 제12권1호
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• pp.13-24
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• 2023

This systematic and meta-analysis aims to evaluate humoral and cellular responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine among kidney transplant recipients (KTRs). We conducted a systematic literature search across databases to evaluate seroconversion and cellular response rates in KTRs receiving SARS-CoV-2 vaccines. We extracted studies that assessed seroconversion rates described as the presence of antibody de novo positivity in KTRs following SARS-CoV-2 vaccination published up to January 23rd, 2022. We also performed meta-regression based on immunosuppression therapy used. A total of 44 studies involving 5,892 KTRs were included in this meta-analysis. The overall seroconversion rate following complete dose of vaccines was 39.2% (95% confidence interval [CI], 33.3%-45.3%) and cellular response rate was 41.6% (95% CI, 30.0%-53.6%). Meta-regression revealed that low antibody response rate was significantly associated with the high prevalence of mycophenolate mofetil/mycophenolic acid (p=0.04), belatacept (p=0.02), and antiCD25 induction therapy uses (p=0.04). Conversely, tacrolimus use was associated with higher antibody response (p=0.01). This meta-analysis suggests that postvaccination seroconversion and cellular response rates in KTRs are still low. And seroconversion rate was correlated with the type of immunosuppressive agent and induction therapy used. Additional doses of the SARS-CoV-2 vaccine for this population using a different type of vaccine are considered.

• Korean Journal of Radiology
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• 제25권3호
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• pp.257-266
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• 2024

Objective: To investigate molecular and functional consequences of additional exposures to iodine- or gadolinium-based contrast agents within 24 hours from the initial intravenous administration of iodine-based contrast agents through an animal study. Materials and Methods: Fifty-six Sprague-Dawley male rats were equally divided into eight groups: negative control, positive control (PC) with single-dose administration of CT contrast agent, and additional administration of either CT or MR contrast agents 2, 4, or 24 hours from initial CT contrast agent injection. A 12 µL/g of iodinated contrast agent or a 0.47 µL/g of gadolinium-based contrast agent were injected into the tail vein. Serum levels of blood urea nitrogen, creatinine, cystatin C (Cys C), and malondialdehyde (MDA) were measured. mRNA and protein levels of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Results: Levels of serum creatinine (SCr) were significantly higher in repeated CT contrast agent injection groups than in PC (0.21 ± 0.02 mg/dL for PC; 0.40 ± 0.02, 0.34 ± 0.03, and 0.41 ± 0.10 mg/dL for 2-, 4-, and 24-hour interval groups, respectively; P < 0.001). There was no significant difference in the average Cys C and MDA levels between PC and repeated CT contrast agent injection groups (Cys C, P = 0.256-0.362; MDA, P > 0.99). Additional doses of MR contrast agent did not make significant changes compared to PC in SCr (P > 0.99), Cys C (P = 0.262), and MDA (P = 0.139-0.771) levels. mRNA and protein levels of KIM-1 and NGAL were not significantly different among additional CT or MR contrast agent groups (P > 0.05). Conclusion: A sufficient time interval, probably more than 24 hours, between repeated contrast-enhanced CT examinations may be necessary to avoid deterioration in renal function. However, conducting contrast-enhanced MRI on the same day as contrast-enhanced CT may not induce clinically significant kidney injury.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.11-19
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• 2024

Acute kidney injury (AKI) is one of the major complications of sepsis. Aurantio-obtusin (AO) is an anthraquinone compound with antioxidant and anti-inflammatory activities. This study was developed to concentrate on the role and mechanism of AO in sepsis-induced AKI. Lipopolysaccharide (LPS)-stimulated human renal proximal tubular epithelial cells (HK-2) and BALB/c mice receiving cecal ligation and puncture (CLP) surgery were used to establish in vitro cell model and in vivo mouse model. HK-2 cell viability was measured using MTT assays. Histological alterations of mouse renal tissues were analyzed via hematoxylin and eosin staining. Renal function of mice was assessed by measuring the levels of serum creatinine (SCr) and blood urea nitrogen (BUN). The concentrations of pro-inflammatory cytokines in HK-2 cells and serum samples of mice were detected using corresponding ELISA kits. Protein levels of factors associated with nuclear factor kappa-B (NF-κB) pathway were measured in HK-2 cells and renal tissues by Western blotting. AO exerted no cytotoxic effect on HK-2 cells and AO dose-dependently rescued LPS-induced decrease in HK-2 cell viability. The concentrations of pro-inflammatory cytokines were increased in response to LPS or CLP treatment, and the alterations were reversed by AO treatment. For in vivo experiments, AO markedly ameliorated renal injury and reduced high levels of SCr and BUN in mice underwent CLP operation. In addition, AO administration inhibited the activation of NF-κB signaling pathway in vitro and in vivo. In conclusion, AO alleviates septic AKI by suppressing inflammatory responses through inhibiting the NF-κB pathway.

• Radiation Oncology Journal
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• 제27권4호
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• pp.194-200
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• 2009

목 적: 위부분절제술 후 방사선치료를 받는 환자들 중에서 위 내 음식물의 배출지연으로 인한 위 용적 및 주변 장기의 위치 변화와 이것의 임상적 의의를 알아보고자 하였다. 대상 및 방법: 2005년 3월 1일부터 2008년 12월 31일까지 위암으로 위부분절제술을 받은 후 보조적 동시항암화학 방사선치료를 받았던 총 32명의 환자들 중, 전산화단층촬영모의치료 영상에서 12시간 이상의 금식에도 불구하고 위 내 음식물이 50 ml 이상 남아 잔존 위의 팽대를 보였던 경우들이 이번 연구 대상이었다. 이 환자들에 대해 방사선치료 기간 동안 주기적으로 시행된 컴퓨터단층촬영 자료를 바탕으로 잔존 위 용적 및 주변 장기들의 위치 변화를 평가하였다. 또한 방사선치료 설계 자료를 바탕으로, 잔존 위 및 주변 장기들의 변화를 고려하지 않고 치료를 지속했을 경우의 치료 표적 및 정상조직의 방사선분포 변화를 알아보았다. 결 과: 총 5명의 전산화단층촬영모의치료 영상에서 배출장애에 의한 50 ml 이상의 위 내 음식물의 저류가 확인되었다. 대상 환자들에서 위 용적은 치료과정 중에 다양한 변화양상을 보였고, 각 환자에서 최대 64.2~340.8 ml (평균, 188.2 ml)의 변화를 보였다. 또한 위 용적에 따라 좌측 신장이 각 환자별 최대 0.7~2.2 cm (평균, 1.2 cm)까지 상하 방향으로 이동하는 양상을 보였다. 모의치료 시의 설계를 위 용적의 변화에 따라 변경하지 않고 치료를 진행한 경우 유의하게 계획용표적체적(V43, 79.5${\pm}$10.4%)에 조사선량이 부족하고 좌측 신장(V20, 34.1${\pm}$12.1%; Mean dose, 23.5${\pm}$8.3 Gy)에 과도한 선량이 조사되는 결과를 얻을 수 있었다. 결 론: 위부분절제술 후 방사선치료를 받는 일부 환자에서 배출지연에 따른 위 용적의 변화와 좌측 신장의 위치변화를 확인할 수 있었다. 배출지연이 발생하는 환자를 선별하여 위 용적의 변화를 파악하고 이를 방사선치료 설계에 반영하는 것이 효과적일 것으로 생각된다.