• Title/Summary/Keyword: agent model

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Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver

  • Heidari, Reza;Esmailie, Neda;Azarpira, Negar;Najibi, Asma;Niknahad, Hossein
    • Toxicological Research
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    • v.32 no.2
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    • pp.133-140
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    • 2016
  • Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

The Effect of Prior Art Search on Patent Output from National R&D Program (선행기술조사가 국가연구개발사업의 성과에 미치는 영향: 특허성과를 중심으로)

  • Im, Bu-Ru;Park, Kyoo-Ho;Lee, Keun
    • Journal of Technology Innovation
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    • v.19 no.1
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    • pp.177-201
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    • 2011
  • This study is trying to estimate the effect of survey of prior art on the technological performance of national R&D program, with the purpose to enhance understanding on the relationship between utilization of patent information and R&D activities. Patent and Technology Trend Research, one of the survey of prior art which gives the information about existing technology and patent trend to the project team has been carried out since 2005. In this paper, effects which Patent and Technology Trend Research has on the technological performance of national R&D projects are estimated by using multiple regression model considering input factors, characteristics of an agent and supplier of money. The result is that Patent and Technology Trend Research has positive and significant effect on the grant and application of domestic and foreign patent. This result can give an hint that the utilization of patent information make the R&D process efficient and effective.

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Effects of Herbal Remedy for Diabetes Mellitus-01 (HRDM-01) on Liver and Serum Lipid Level in Diabetic Rats (당뇨한약복합처방(Herbal Remedy for Diabetes Mellitus-01, HRDM-01)이 당뇨병성 흰쥐의 간 및 혈중 지질에 미치는 영향)

  • Kim, Hyung-Woo;Ha, Tae-Hoon;Cho, Myung-Rae;Cho, Su-In
    • The Korea Journal of Herbology
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    • v.25 no.3
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    • pp.117-121
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    • 2010
  • Objective:The Herbal Remedy for Diabetes Mellitus-01 (HRDM-01) is composed of 11 species of medicinal plants. HRDM-01 is used as anti-hyperglycaemic agent. Anti-hyperglycaemic agents in western medicine often have hepatotoxicities. Therefore, we investigated safety of HRDM-01, especially in liver functions. Methods:We investigated the effects of HRDM-01 on liver function measuring serum AST, ALT and LDH levels and histopathological changes of liver tissue using photomicroscope. In addition, we also investigated the effects on serum lipid levels such as total cholesterol, HDL-cholesterol and triglyceride. Results:In our experiment, single injection of streptozotocin elevated levels of AST and ALT in serum. But LDH level was not affected. In addition, our animal model showed elevated levels of total cholesterol and triglyceride in serum. 30 days treatment with HRDM-01 lowered serum AST level. Serum levels of ALT and LDH did not affected. In addition, HRDM-01 lowered serum triglyceride level significantly. In histopathological observation, we did not find any abnormal changes in all experimental groups. Conclusions:Briefly, HRDM-01 did not elevate serum levels of ALT, LDH, total cholesterol and did not affect histopathological changes in liver tissues. Moreover, HRDM-01 lowered serum AST, triglyceride, which are elevated by induction of diabetes mellitus. These results suggest the safety of HRDM-01 in diabetic treatment.

The Effects of Phellodendri Cortex Ex on Experimental Rat Model of Benign Prostatic Hyperplasia (황백(黃柏)이 전립선비대증(前立腺肥大症) Rat에 미치는 영향)

  • Park, Jung-Jun;Lee, Jang-Sik;Kim, Young-Seung
    • Korean Journal of Oriental Medicine
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    • v.16 no.2
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    • pp.131-141
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    • 2010
  • Objective : Benign prostatic hyperplasia(BPH) is one of the most common diseased among elderly men. BPH can be treated with alpha-1 adrenergic blocker or $5{\alpha}$-reductase inhibitor(Finasteride) that reduces serum dihydrotestosterone(DHT). Phellodendri Cortex Ex has been broad studied on its chemical components, pharmacological activity, and clinical effects on anti-inflammation, anti-allergy, anti-tumor, immunity, antibacteria and other bioactivities. In this study, we investigated the therapeutic effects and action mechanism of Phellodendri Cortex Ex with a BPH induced by castration and testosterone treatment. Methods : Sprague-Dawley rats were treated with testosterone after castration for induction of experimental benign prostatic hyperplasia, which is similar to human benign prostatic hyperplasia in histopathological profiles. Phellodendri Cortex as an experimental specimen, and Finasteride as a positive control, were administered orally. The prostates were evaluated by histopathological changes, and the expression of $5{\alpha}$-reductase genes. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Phellodendri Cortex Ex showed a diminished range of the tissue damage. In the reverse transcription-polymerase chain reaction(RT-PCR) of $5{\alpha}$-reductase genes, Phellodendri Cortex inhibited the expression of $5{\alpha}$-reductase genes. Conclusions : These findings suggest that Phellodendri Cortex Ex may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the suppression of $5{\alpha}$-reductase. From these results, we suggest that Phellodendri Cortex Ex could be a useful agent for treating the benign prostatic hyperplasia.

Protective Effect of Lonicerae Flos Aqueous Extracts on a Pressure Overload-induced Heart Failure Model

  • Shin, Jae-wook;Jang, Woo-seok;Baek, Kyung-min
    • The Journal of Internal Korean Medicine
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    • v.38 no.6
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    • pp.877-890
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    • 2017
  • Objectives: Lonicerae flos (LF), a dried flower part of Lonicera japonica Thunb., has been widely used in Korean medicine as anti-inflammatory and antioxidative agent. The purpose of this study was to determine the cardioprotective effects of LF, through potential antioxidant effects, on the pressure overload (PO)-induced heart failure (HF) in C57BL/6 mice after transverse aortic constriction (TAC) surgery. Methods: Resveratrol (10 mg/kg body weight) or LF (125, 250 or 500 mg/kg body weight) was orally administered, once daily for 14 days, starting 14 days after TAC surgery. Changes in the mortality, body weights, heart weights, histopathology of the heart, and antioxidant defense systems of the heart were analyzed. Results: Marked and noticeable increases of heart weights, mortalities, and hypertrophic, focal, and lytic fibrotic histological changes in the LVs were observed, with destruction of heart antioxidant defense systems after surgery. However, HF signs, induced by TAC surgery through PO, and destruction of heart antioxidant defense systems were significantly and dose-dependently inhibited by 14 days of maintained oral treatment with LF 500, 250 or 125 mg/kg. Treatment with 250 mg/kg LF was comparable to treatment with 10 mg/kg resveratrol. Conclusions: The results in this study suggest that oral administration of LF favorably relieves PO-induced HF following TAC, through increase of heart antioxidant defense systems. The overall effects of 250 mg/kg LF were similar to those of 10 mg/kg resveratrol. More detailed mechanistic studies should be conducted in the future, with screening of the biologically active compounds in LF.

Immune-enhancing Effect of Mubigangjang-Ju (무비강장주의 면역증진 효과)

  • Shin Soon Shik;Kim Bo Kyung;An Chang Su;Kim Gyeong Cheal
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.436-439
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    • 2004
  • Mubigangjang-Ju (MGJ) is a traditional wine, fermented extract of Cynanchum wilfordii, Angelicae gigantis and Epimedium koreanum etc. In the present study, we comparatively investigated the immune-enhancing effect of fermented extract (MGJ) and water extract (WE). Forced swimming test (FST) was performed as a model of activity test in mice and measured blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), glucose (Glc) and total protein (TP) in the serum. Each extracts were orally administered into mice, 10 ㎖/kg, once per day for 7 days using a feeding atraumatic needle. After 3 days, on FST, the immobility time was decreased in the MGJ-fed group (133.7±18.6 s) in comparison with the saline-fed group (155.8±16.6 s). After 7 days, the immobility time was significantly decreased in the MGJ-fed group (105.3±12.7 s) in comparison with the saline-fed group (171.3±8.1 s). In addition, the content of AST was significantly decreased and the contents of BUN, ALT and LDH in the blood serum was also decreased. Whereas, the content of Glc tend to increase and TP level was not changed. However, WE had no effect on all experiments. The present results suggest that fermented extract was more effective than water extract and it may be useful for the immune-enhancing agent.

Characterization of valacyclovir transport mechanism across the intestinal epithelium

  • Han, H.;Covitz, M.;Surendran, N.;Stewart, B.;Amidon, G.L.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.119-119
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    • 1997
  • Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

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Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean Red Ginseng Prevent Rotavirus Infection in Newborn Mice

  • Yang, Hui;Oh, Kwang-Hoon;Kim, Hyun Jin;Cho, Young Ho;Yoo, Yung Choon
    • Journal of Microbiology and Biotechnology
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    • v.28 no.3
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    • pp.391-396
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    • 2018
  • It is well known that Korean red ginseng has various biological activities. However, there is little knowledge about the antiviral activity of Korean red ginseng and its ginsenosides. In this study, we addressed whether oral administration of ginsenoside-Rb2 and -Rg3 is able to protect against rotavirus (RV) infection. The protective effect of ginsenosides against RV infection was examined using an in vivo experiment model in which newborn mice (10-day-old) were inoculated perorally (p.o.) with $1.5{\times}10^6$ plaque-forming units/mouse of RV strain SA11. When various dosages of ginsenoside-Rb2 (25-250 mg/kg) were administered 3days, 2 days, or 1 day before virus challenge, treatment with this ginsenoside at the dosage of 75 mg/kg 3days before virus infection most effectively reduced RV-induced diarrhea. In addition, consecutive administration of ginsenoside-Rb2 (75 mg/kg) at 3 days, 2 days, and 1 day before virus infection was more effective than single administration on day -3. The consecutive administration of ginsenoside-Rb2 also reduced virus titers in the bowels of RV-infected mice. In an experiment to compare the protective activity between ginsenoside-Rb2 and its two hydrolytic products (20(S)- and 20(R)-ginsenoside-Rg3), 20(S)-ginsenoside-Rg3, but not 20(R)-ginsenoside-Rg3, prevented RV infection. These results suggest that ginsenoside-Rb2 and its hydrolytic product, 20(S)-ginsenoside-Rg3, are promising candidates as an antiviral agent to protect against RV infection.

Biosynthesized Platinum Nanoparticles Inhibit the Proliferation of Human Lung-Cancer Cells in vitro and Delay the Growth of a Human Lung-Tumor Xenograft in vivo -In vitro and in vivo Anticancer Activity of bio-Pt NPs-

  • Bendale, Yogesh;Bendale, Vineeta;Natu, Rammesh;Paul, Saili
    • Journal of Pharmacopuncture
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    • v.19 no.2
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    • pp.114-121
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    • 2016
  • Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

Numerical Investigation of the Urea Melting and Heat Transfer Characteristics with Three Different Types of Coolant Heaters (냉각수 순환 방식 가열원 형상에 따른 요소수 해동 특성에 관한 수치적 연구)

  • Lee, Seung-Yeop;Kim, Man-Young;Lee, Chun-Hwan;Park, Yun-Beom
    • Transactions of the Korean Society of Automotive Engineers
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    • v.20 no.4
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    • pp.125-132
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    • 2012
  • Urea-SCR system, which converts nitrogen oxides to nitrogen and water in the presence of a reducing agent, usually AdBlue urea solution, is known as one of the powerful NOx reduction systems for mobile as well as stationary applications. For its consistent and reliable operation in mobile applications, such various problems as transient injection, ammonia slip, and freezing in cold weather have to be resolved. In this work, therefore, numerical study on three-dimensional unsteady heating problems were analyzed to understand the melting and heat transfer characteristics such as urea liquid volume fraction, temperature profiles and generated natural convection behavior in urea solution by using the commercial software Fluent 6.3. After validating by comparing numerical and experimental data with pure gallium melting phenomena, numerical experiment for urea melting is conducted with three different coolant heating models named CH1, 2, and 3, respectively. Finally, it can be found that the CH3 model, in which more coolant is concentrated on the lower part of the urea tank, has relatively better melting capability than others in terms of urea quantity of $1{\ell}$ for start-up schedule.