• Radiation Oncology Journal
• /
• v.34 no.3
• /
• pp.223-229
• /
• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• Asian-Australasian Journal of Animal Sciences
• /
• v.26 no.10
• /
• pp.1399-1405
• /
• 2013

The present study focused on establishing the effects of interferon-gamma (IFN-${\gamma}$) on interleukin-18 (IL-18) expression patterns and pregnancy outcomes in pregnant rats. Pregnant rats at the post-implantation stage were randomized into control, low IFN-${\gamma}$ (L-IFN-${\gamma}$) and high IFN-${\gamma}$ groups (H-IFN-${\gamma}$) that received normal saline, 100 IU/g of IFN-${\gamma}$ and 500 IU/g of IFN-${\gamma}$ vaginal muscular injection, respectively. The effects of IFN-${\gamma}$ on IL-18 expression and pregnancy outcomes were assessed systematically using several methods, including immunohistochemistry streptavidin-perosidase (SP), image pattern analysis, enzyme-linked immune-sorbent assay (ELISA), whole blood count (WBC) count, microscopy and visual observation. IL-18 was detected in the uteri of all pregnant rats, and mainly distributed in the endometrium, decidual cells, vascular endothelium and myometrium. Immunohistochemistry and image pattern analyses revealed significantly lower IL-18 expression in the H-IFN-${\gamma}$ group compared to the L-IFN-${\gamma}$ and control groups (p<0.01), indicating that high doses of IFN-${\gamma}$ induce downregulation of IL-18 in the uterus of pregnant rats. ELISA results disclosed that IL-18 expression in peripheral blood of the H-IFN-${\gamma}$ group was lower than that of the L-IFN-${\gamma}$ group (p<0.05), and significantly reduced compared to the control group (p<0.01). Moreover, the number of peripheral leukocytes in the H-IFN-${\gamma}$ group was significantly higher than those in the control and L-IFN-${\gamma}$ groups (p<0.01). Morphology analysis showed no evident differences between the L-IFN-${\gamma}$ and control groups. However, for the H-IFN-${\gamma}$ group, uterine mucosa bleeding, necrosis and excoriation were observed using microscopy. Visual observation revealed marroon, swelling, crassitude and no embryo in the uterus, which are obvious indicators of abortion. These results indicate that IFN-${\gamma}$ plays a regulatory role in IL-18 expression in the uterus and peripheral blood of pregnant rats at the post-implantation stage. Moreover, high levels (500 IU/g) of IFN-${\gamma}$ influence normal pregnancy at the early stages in rats by downregulating IL-18 expression in the uterus and peripheral blood and increasing the number of peripheral leukocytes, consequently triggering termination of pregnancy.

• Journal of Animal Science and Technology
• /
• v.56 no.2
• /
• pp.6.1-6.4
• /
• 2014

The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic ${\alpha}$-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, $10.0{\mu}g/kg$ BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of $10.0{\mu}g/kg$ body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p < 0.05). Although there was no statistically significant, the ${\alpha}$-amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down-regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.

• Applied Microscopy
• /
• v.31 no.1
• /
• pp.37-47
• /
• 2001

In order to investigate a pathogenesis of liver damage induced by skin burn, thermal injury was induced by scald burn on entirely dorsal surface in rats (total burn surface area $20\sim25\%$) except for inhalated injury. At 5 and 24 h after scald burn, biochemical assay and morphological changes in serum and liver tissue were examined. Skin burn increased liver weight (% of body weight, p<0.05) and the activity of serum aniline amino-transferase (ALT, p<0.05), in addition, the activity of xanthine oxidase (XO), an enzyme of oxygen free radical generating system, was elevated (p<0.01) in serum, but not in skin and in liver. Postburn treatment of allopurinol intraperitoneally decreased liver weight, serum ALT activity and serum XO activity. Scald burn induced ultrastructurally swelling of endoplasmic reticulum, ribosome detachment, accumulation of lipid, dilatation of bile canaliculi and intercellular space, neutrophil infiltration, activation of Kupffer's cells and degeneration of hepatocytic microvilli. Futhermore , thermal injury decreased not only the protein concentration in plasma but also the number of intravascular leukocytes, that indicates induction of edema formation with protein exudation and inflammation by neutrophil infiltration into the internal organs. However allopurinol injection after burn inhibited post burn ultrastructural changes. These data suggest that acute dermal scald burn injury leads to liver damage, that is related to elevation of xanthine oxidase activity in serum. Xanthine oxidase may be a key role in the pathogenesis of liver damage induced by skin burn.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.26 no.1
• /
• pp.5-17
• /
• 2000

To evaluate the possible therapeutic effects of growth hormone and vitamin C on multiorgan failure, a rat model was developed for LPS-induced sepsis. Using this model, the effects of growth hormone and vitamin C on tissue damages, catalase and i-NOS activities, and MDA levels were examined in the lung and liver. The level of TNF- in plasm was also examined. Male, Sprague-Dawley rats were injected with LPS intraperitoneally then divided into 3 groups : positive controls injected with LPS only, the ones injected with growth hormone or vitamin C immediately after the LPS injections. The lung and the liver were then isolated, blood samples were collected at 24 or 48 hours after the LPS injection, then examined for histopathological and biochemical changes. The results obtained were as follows. 1. LPS induced sinusoid vasodilation and mild destruction of lobular structure in the liver. In the lung, alveolar structure appeared to be thickened and interstitial edema was observed. The levels of MDA in the liver and the lung was increased by LPS, while the activity of catalase was decreased. The activity of i-NOS of those tissues was also increased, which was more pronounced at 24 hr. The level of TNF- in plasm was increased by LPS 2. In the lung, vitamin C suppressed lymphocyte and neutrophil infiltration, alveolar wall thickening and interstitial edema. In the liver, vitamin C protected against the destruction of the lobular structure. The activity of catalase reduced by LPS was reversed partly by vitamin C. The activity of i-NOS enhanced by LPS was also reversed by vitamin C. The level of TNF- in plasm reduced in some animals by vitamin C, which however was not significant statistically(p<0.05). 3. Growth hormone showed similar protective effects against inflammation and damages in the liver and lung tissues. Growth hormone reversed partly the LPS effects on the level of MDA, the activity of catalase and i-NOS induction in the liver and the lung. Growth hormone reduced plasma level of TNF-${\alpha}$ substantially, which contrasted from vitamin C. Besides this, overall protective effects of growth hormone against LPS-induced experimental sepsis were similar to those of vitamin C. From this results, the mechanism of growth hormone on suppression of LPS-induced tissue damage might be associated with production of antioxidative enzyme and suppression of plasma TNF- level.

• Journal of Acupuncture Research
• /
• v.32 no.2
• /
• pp.187-195
• /
• 2015

Objectives : The purpose of this study is evaluating the effect of Poria cocos pharmacopuncture (PCP) at $SP_6$(Sameumgyo) and $ST_{36}$(Joksamni) on chronic stress model(CSM) rats. Methods : The experimental rats were assigned to five groups: normal, CSM(control), PCP1X, PCP2.5X and PCP5X. The experimental rats in CSM(control), PCP1X, PCP2.5X and PCP5X were put through a timetable to cause CSM. PCP($20{\mu}l$) was administered at $SP_6$, $ST_{36}$ to groups PCP1X, PCP2.5X and PCP5X once every three days for a total of six times. The weight of the rats was measured by an electronic scale after PCP injection, once every three days for a total of six times. Blood samples were taken from the rats for analysis of aspartate aminotransferase(AST) and alanine aminotransferase(ALT). Serotonin and norepinephrine were measured by enzyme-linked immunosorbent assay(ELISA) kit. Results : The experimental groups(PCP1X, 2.5X, 5X) showed significant body weight increase compared to the control group. Regarding AST and ALT changes in serum, the experimental groups(PCP2.5X, 5X) showed a significant decrease compared to the control group. For Serotonin changes in serum, the experimental group(PCP5X) showed a significant increase compared to the control group. For Norepinephrine changes in serum, the experimental groups(PCP2.5X) showed a significant decrease compared to the control group. Conclusions : These data suggest that PCP at $SP_6$, $ST_{36}$ has therapeutic effects on CSM rats.

• Journal of Ginseng Research
• /
• v.44 no.2
• /
• pp.291-299
• /
• 2020

Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg₁, Re, Rb₁, Rc, Rb₂, Rb₃, Rd, Rk₃, Rh₄, 20 (S)-Rg₃, 20 (R)-Rg₃, Rk₁, Rg₅, salidroside, and so on. Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G₂/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. Conclusion: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.

• Journal of Life Science
• /
• v.13 no.4
• /
• pp.457-462
• /
• 2003

Houttuynia Cordata thunb has been used as folk medicine for analgesics, beriberi, edema, hepatitis and icterus etc. We investigated, the effects of Houttuynia Cordata thunb administration on protective in liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) treated rats. Seven days after the injection of TCDD(1${\mu}g$/kg), Houttuynia Cordata thunb (200mg/kg) was administered into rats intraperitoneally for four weeks. We examined the antioxidative enzymatic activity by measuring the level of GOT, GPT in serum and MDA, GSH, GSSG, GPx, SOD and Catalase in liver tissue of rats. GOT activity of Houttuynia Cordata thunb and TCDD administered group(HTT) showed 49.00% of inhibitive effect compared to TCDD-treated abnormal group(TTA). GPT level of HTT group was decreased to the level of Non TCDD-treated group(NTT). MDA content in the TTA group was 1.27 times increased compared to NTT group. HTT group was inhibited by 69.53% compared to TTA group. GSH contents in HTT group was 1.91 times increased compared to TTA group. GSSG contents in HTT group was 46.72% decreased compared to TTA group. SOD and Catalase in TTA group were lower than in NTT group, but SOD and Catalase in HTT group were increased by 82% and 55.45% respectively compared to TTA group.

• Molecules and Cells
• /
• v.40 no.2
• /
• pp.133-142
• /
• 2017

Previous studies have shown that bone marrow mesenchymal stromal cell (MSC) transplantation significantly improves the recovery of neurological function in a rat model of intracerebral hemorrhage. Potential repair mechanisms involve anti-inflammation, anti-apoptosis and angiogenesis. However, few studies have focused on the effects of MSCs on inducible nitric oxide synthase (iNOS) expression and subsequent peroxynitrite formation after hypertensive intracerebral hemorrhage (HICH). In this study, MSCs were transplanted intracerebrally into rats 6 hours after HICH. The modified neurological severity score and the modified limb placing test were used to measure behavioral outcomes. Blood-brain barrier disruption and neuronal loss were measured by zonula occludens-1 (ZO-1) and neuronal nucleus (NeuN) expression, respectively. Concomitant edema formation was evaluated by H&E staining and brain water content. The effect of MSCs treatment on neuroinflammation was analyzed by immunohistochemical analysis or polymerase chain reaction of CD68, Iba1, iNOS expression and subsequent peroxynitrite formation, and by an enzyme-linked immunosorbent assay of pro-inflammatory factors (IL-$1{\beta}$ and TNF-${\alpha}$). The MSCs-treated HICH group showed better performance on behavioral scores and lower brain water content compared to controls. Moreover, the MSC injection increased NeuN and ZO-1 expression measured by immunochemistry/immunofluorescence. Furthermore, MSCs reduced not only levels of CD68, Iba1 and pro-inflammatory factors, but it also inhibited iNOS expression and peroxynitrite formation in perihematomal regions. The results suggest that intracerebral administration of MSCs accelerates neurological function recovery in HICH rats. This may result from the ability of MSCs to suppress inflammation, at least in part, by inhibiting iNOS expression and subsequent peroxynitrite formation.

• Nutritional Sciences
• /
• v.9 no.1
• /
• pp.20-28
• /
• 2006

Aryl sulfotransferase (AST) IV is a liver enzyme involved in detoxication and has been shown to be susceptible to down regulation by a number of hepatotoxic xenobiotics. Studies presented here to investigate the ability of biological and non-biological divalent metal cations on AST IV activity showed that AST IV was strongly inhibited following in vitro or in vivo exposure to. Zn ( II ), Co ( II ) or Cd ( II ). It was found that $0.025\sim$2.5 uM of these metal ions were sufficient to cause $50\%$ of inhibition in vitro in purified AST IV and $0.25\sim$25 uM of these metal ions in liver cytosolic fractions. For the in vivo study, 1,000 mg Cu ( II )/kg, 2,000 mg Zn ( II )/kg or 250 mg Cd( II )/kg was added to individual diets and administered to three (3) group; of mts over a 7 week period The Co ( II )-supplemented diet produced no apparent change in rat growth rate and resulted in 30-fold increase in liver cytotolic Cu ( II ) levels, suggesting that elevated levels of Cu ( II ) ion in the liver were responsible for the loss of AST IV activity. In contrast, the Zn ( II )-supplemented diet caused a decrease in rat growth rates and resulted in zero increase in liver Zn ( II ) levels, which suggested an indirect inhibition mechanism was caused by Zn ( II ) in the liver. Rats were fed the Cd-supplemented diet also displayed a decrease in growth rate with little or no change in liver Cu ( II ) or Zn ( II ) levels. When the liver cytosols of mts from the metal ion diets were immunochemically analyzed for the AST IV and albumin contents, no significant changes were observed in albumin levels. However, AST IV contents in the cytosols of mts fed the Zn ( II )-supplemented diets showed a slight decrease in amount These results showed that AST IV activity in vitro and in vivo can be inhibited by Co ( II ), Zn ( II ), and Cd ( II ) by apparently different mechanisms. The immediate response to a Zn injection showed a decrease in AST IV activity but not in the AST IV content in liver cytosol. These mechanisms appeared to involve direct actions of the metal ion on AST IV activity and indirect actions affecting AST IV amount.