• Journal of Ginseng Research
• /
• 제41권2호
• /
• pp.159-168
• /
• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

• 대한한의학방제학회지
• /
• 제25권2호
• /
• pp.155-166
• /
• 2017

Objectives : Polygoni Multiflori Ramulus has been widely used as a traditional medicinal herb for the treatment of insomnia, limb pain and itch. The extract of Polygoni Multiflori Ramulus (PMRE) is known to have a modulatory effect of many inflammatory responses. This study was performed to investigate the hepatoprotective effect of PMRE against arachidonic acid (AA) + iron-induced oxidative stress on HepG2 cell and carbon tetrachloride ($CCl_4$)-induced liver injury on mice. Methods : The effects of PMRE on cell viability was assessed by MTT assay. And flow cytometric analysis was performed to estimate the effects on mitochondrial function. To investigate its underlying mechanism, apoptosis-related proteins were analysed by using immunoblot analysis. In addition, ICR mouse were administrated (po) with the PMRE (30, 100 mg/kg) for 3 days and then, injected (ip) with $CCl_4$ (0.5 ml/kg body weight) to induce acute liver damage. The level of pro-caspase-3 was measured. Results : Treatment of PMRE increased relative cell viability, prevented a cleavage of poly (ADP ribose) polymerase and pro-caspase-3, and also reduced mitochondrial membrane permeability against AA + iron-induced oxidative stress. In addition, PMRE treatment decreased liver injury induced by $CCl_4$, as evidenced by increases in pro-caspase-3 level. Conclusions : These results demonstrate that PMRE has an ability to anti-oxidant and hepatoprotective effect against AA + iron-induced oxidative stress and $CCl_4$-induced liver injury.

• 대한한의학방제학회지
• /
• 제11권2호
• /
• pp.135-146
• /
• 2003

Objectives : Wolguk-whan has been used as a prescription of natural drug for the treatment of stress digestive system disease. Recently, we reported that Wolguk-whan methnol extract (WGWM) exerted a significant protective effect against oxidative damage to the liver of ICR mice. This study was purposed to investigate the effects of Wolguk-whan water extract (WGWW) on liver injury induced by oxidative stress. Methods : In order to investigate the effects of WGWW on acute liver injury, ICR mice were pretreated with WGWW for 6days, starved for 24hrs, and administerated acetamirtophen(500mg/kg, i.p.). In the liver homogenates, lipid peroxide and glutathione(GSH) levels were measured. In addition, activities of hepatic enzyme, such as catalase, glutathione peroxidase(GSH-Px), glutathione S-transferase(GST) were measured in the hepatic mitochondrial and cytosolic fractions. Results : In vivo administeration of WGWW showed effective inhibition of acetaminophen induced lipid peroxidation, and showed elevations of GSH level, catalase, GSH-Px, GST activities. Conclusions : These results suggested that WGWW might suppress the formation of oxidative metabolites, and prevent acetaminophen induced hepatotoxicity.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권12호
• /
• pp.5071-5074
• /
• 2016

Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague-Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a rat model of colon cancer.

• 대한한의학방제학회지
• /
• 제32권3호
• /
• pp.263-275
• /
• 2024

Background : Recent studies have shown that stress fundamentally influences the functional modulation of organ and stress-related disease causes high morbidity and mortality rates. Objective : The present research investigated the effect of restraint stress on psychological and physiological responses. Results : Body weight and food intake were changed in stress group. Body weight has continuously decreased, and food intake has been slightly altered. As a result of measuring each tissue's weight, the liver and kidney's weight loss was greater than that of other organs. The lipid profile of stressed animals showed significant increases in cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels compared to control. As hepatic marker enzymes, serum glutamic pyruvic transaminase (GPT; alanine aminotransferase), glutamic oxalacetic transaminase (GOT; aspartate aminotransferase), and lactic dehydrogenase (LDH) were increased in the stress group. However, levels of serum cortisol and corticosterone did not affect. Results of the behavioral tests show that the stress group has increased activity, sluggish movements, and anxiety in the central part compared with the control group through the open field test. In the forced swim test, the stress group models had a longer duration of slowing movement, and its rate also increased. Also, in immunoblotting, stress increased the inflammatory factors Inducible Nitric Oxide Synthase (iNOS), cyclooxygenase-2 (COX-2) and activated the mitogen-activated protein kinase (MAPK) pathway. Conclusions : We observed that mouse model were affected behavioral response and liver injury when exposed to restraint stress, indicating the importance of the restraint stress in the development of psychological and physiological processes.

• Toxicological Research
• /
• 제32권2호
• /
• pp.133-140
• /
• 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.

• Toxicological Research
• /
• 제22권4호
• /
• pp.323-328
• /
• 2006

Global gene expression profile was analyzed by microarray analysis of rat liver RNA after acute acetaminophen (APAP) administration. A single dose of 1g/kg body weight of APAP was given orally, and the liver samples were obtained after 24, 48 h, and 2 weeks. Histopathologic and biochemical studies enabled the classification of the APAP effect into injury (24 and 48 h) and regeneration (2 weeks) stages. The expression levels of 4900 clones on a custom rat gene microarray were analyzed and 484 clones were differentially expressed with more than a 1.625-fold difference(which equals 0.7 in log2 scale) at one or more time points. Two hundred ninety seven clones were classified as injury-specific clones, while 149 clones as regeneration-specific ones. Characteristic gene expression profiles could be associated with APAP-induced gene expression changes in lipid metabolism, stress response, and protein metabolism. We established a global gene expression profile utilizing microarray analysis in rat liver upon acute APAP administration with a full chronological profile that not only covers injury stage but also later point of regeneration stage.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권2호
• /
• pp.169-173
• /
• 2013

Renal ischemia-reperfusion (IR) causes remote liver damage. Oxytocin has anti-inflammatory and antioxidant effects. The main purpose of this study was to evaluate the protective function of oxytocin (OT) in remote liver damage triggered by renal IR in rats. Twenty four rats were randomly divided into four different groups, each containing 8 rats. The groups were as follows: (1) Sham operated group; (2) Sham operated+OT group (3) Renal IR group; (4) Renal IR+OT group. OT ($500{\mu}g/kg$) was administered subcutaneously 12 and 24 hours before and immediately after ischemia. At the end of experimental procedure, the rats were sacrificed, and liver specimens were taken for histological assessment or determination of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), paraoxonase (PON-1) activity and nitric oxide (NO). The results showed that renal IR injury constituted a notable elevation in MDA, TOS, Oxidative stress index (OSI) and significantly decreased TAS, PON-1 actvity and NO in liver tissue (p<0.05). Additionally renal IR provoked significant augmentation in hepatic microscopic damage scores. However, alterations in these biochemical and histopathological indices due to IR injury were attenuated by OT treatment (p<0.05). These findings show that OT ameliorates remote liver damage triggered by renal ischemia-reperfusion and this preservation involves suppression of inflammation and regulation of oxidant-antioxidant status.

• Journal of Nutrition and Health
• /
• 제54권4호
• /
• pp.412-421
• /
• 2021

본 연구는 TAA 복강투여로 유발된 간 손상 동물모델에서 인진호 열수 추출물의 간보호 효능을 평가하였으며 다음과 같은 결론을 얻었다. TAA로 인해 줄어드는 체중은 인진호 열수 추출물을 투여한 군에서 유의하게 증가하였으며, 간손상에 의해 증가한 혈중 암모니아 함량과 MPO 활성은 인진호 열수 추출물 투여군에서 유의하게 감소하였다. 간 조직의 western blotting 결과, 인진호 열수 추출물 투여가 산화적 스트레스 관련 인자들의 발현을 유의적으로 감소시키고, 항산화 관련 인자들의 발현을 유의하게 증가시켰으며, MMPs의 발현은 감소시키고 TIMP-1의 발현은 증가시킴을 확인할 수 있었다. 따라서 인진호 열수 추출물은 TAA로 유발된 간손상 동물모델에서 항산화 작용을 통해 산화적 스트레스를 억제하여 간보호 효과를 보이는 것으로 판단된다.

• Molecules and Cells
• /
• 제41권5호
• /
• pp.401-412
• /
• 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.