• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.775-780
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• 2014

Objectives: TCR-gamma-delta+T cells (${\gamma}{\delta}$ T cells) are non-conventional T lymphocytes that can recognize and eradicate tumor cells. Our previous studies showed that infiltration and function of ${\gamma}{\delta}$ T cells were substantially attenuated in hepatocellular carcinoma (HCC). However, their prognostic value was not clarified. Methods: The association between ${\gamma}{\delta}$ T cells and the clinical outcomes was determined by immunohistochemistry (IHC) in a HCC patient cohort (n = 342). Results:Immunohistochemistry showed decreased infiltration of ${\gamma}{\delta}$ T cells in tumoral tissues compared with paired peritumoral tissues. The counts of ${\gamma}{\delta}$ T cells in peritumoral tissues were negatively correlated with tumor size (P = 0.005). Survival analysis showed that the levels of peritumoral ${\gamma}{\delta}$T cells were related to both time to recurrence (TTR) and overall survival (OS) (P = 0.010 and P = 0.036, respectively) in univariate analysis, and related to TTR in multivariate analysis (P = 0.014, H.R. [95% CI] = 0.682 [0.502-0.927]). Furthermore, the level of peritumoral ${\gamma}{\delta}$ T cells showed independent prognostic value for TTR in Barcelona Clinic Liver Cancer (BCLC) stage A patients (P = 0.038, H.R. [95% CI] = 0.727 [0.537-0.984]). However, tumoral ${\gamma}{\delta}$ T cells did not show independent prognostic value for either TTR or OS in HCC patients. Conclusions: Low counts of ${\gamma}{\delta}$ T cells in peritumoral liver tissue are related to a higher incidence of recurrence in HCC and can predict postoperative recurrence, especially in those with early-stage HCC.

• Journal of Nutrition and Health
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• v.5 no.2
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• pp.91-103
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• 1972

Zinc is one of the essential trace elements in the living organism for growth and health. The first identified metalloenzyme, carbonic anhydrase, is a zinc compound and several others have been described since. Among zinc deficiency syndromes in animals porcine parakeratosis has been successfully treated with zinc supplements, and in man a syndrome of anemia, hypogonadism, hepatosplenomegaly, and dwarfism, prevalent in parts of Iran and Egypt, has been ascribed to lack of zinc in the diet. Dietary zinc excess in the rat is manifested by a hypochromic, microcytic anemia, poor growth, reduction in liver catalase and cytochrome oxidase. The present study is an attempt to delineate the changes of tissue contents of trace elements, especially of iron, copper and zinc in liver and kidneys of the rats. Weanling albino rats, weighing 60 to 80gm. were used in this experiments. The rats were housed in cages with aluminum floors and received feed and distilled water ad libitum. Animals were divided into three groups, control, low zinc diet and high zinc diet groups. The high zinc diet group was subdivided into 0.5% Zn and 0.7%Zn groups. The supplementary copper or iron was added to the high dietary zinc groups. The animals were sacrificed and the tissues were washed several times with deionized water. The wet digested samples were analyzed by Hitachi Model 207 atomic absorption spectro-photometer for the determination of iron, copper and zinc in the liver and kidney. Hemoglobin level in the blood was measured by cyanmethemoglobin method. The results of this study are as follows: 1) All rats fed high zinc diets and low zinc diets gained less weight than control. Weight gain was not improved by the supplementary copper or iron and both. 2) Hemoglobin concentration was decreased significantly in the rats fed high zinc diets and less in the low zinc diet. Supplementary copper and iron to the higher zinc diet appeared to give some improvement of anemia. 3) The iron contents of the liver and kidneys were significantly decreased in the high zinc groups and the reduction was more significantly in the rats receiving higher zinc diet (0.7%). The supplementary copper caused a further depression of liver iron. On the other hand, the iron, added to the high zinc diet lessoned the severity of the decrease in liver iron and caused kidney iron to be maintained almost at the level found in the rats fed by zinc and supplementary copper diet. 4) High zinc diets did not change copper content of the liver and kidney. Supplementary copper elevated the concentration in the liver and kidney and added iron had no effect on the accumulation of copper in the liver and kidneys. 5) The high zinc diets caused marked increases of zinc content in the liver and kidney. Supplementary iron to the high zinc diet caused increases of zinc contents of liver and kidneys.

• The Journal of Internal Korean Medicine
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• v.44 no.3
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• pp.402-417
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• 2023

Objective: Liver fibrosis is a highly conserved wound-healing response and the final common pathway of chronic inflammatory injury. This study aimed to evaluate the potential anti-fibrotic effect of the combination of Rhei Radix et Rhizoma water extract (RW) and silymarin in a thioacetamide (TAA)-induced liver fibrosis model. Methods: The liver fibrosis mouse model was established through the intraperitoneal injection of TAA (1 week 100 mg/kg, 2-3 weeks 200 mg/kg, 4-8 weeks 400 mg/kg) three times per week for eight weeks. Animal experiments were conducted in five groups; Normal, Control (TAA-induced liver fibrosis mice), Sily (silymarin 50 mg/kg), RSL (RW 50 mg/kg+silymarin 50 mg/kg), and RSH (RW 100 mg/kg+silymarin 50 mg/kg). Biochemical analyses were measured in serum, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and ammonia levels. Liver inflammatory cytokines and fibrous biomarkers were measured by Western blot analysis, and liver histopathology was evaluated through tissue staining. Results: A significant decrease in the liver function markers AST and ALT and a reduction in ammonia and total bilirubin were observed in the group treated with RSL and RSH. Measurement of reactive oxygen species and MDA revealed a significant decrease in the RSL and RSH administration group compared to the TAA induction group. The expression of extracellular matrix-related proteins, such as transforming growth factor β1, α-smooth muscle actin, and collagen type I alpha 1, was likewise significantly decreased. All drug-administered groups had increased matrix metalloproteinase-9 but a decreasing tissue inhibitor of matrix metalloproteinase-1. RSL and RSH exerted a significant upregulation of NADPH oxidase 2, p22^phox, and p47^phox, which are oxidative stress-related factors. Furthermore, pro-inflammatory proteins such as cyclooxygenase 2 and interleukin-1β were markedly suppressed through the inhibition of nuclear factor kappa B activation. Conclusions: The administration of RW and silymarin suppressed the NADPH oxidase factor protein level and showed a tendency to reduce inflammation-related enzymes. These results suggest that the combined administration of RW and silymarin improves acute liver injury induced by TAA.

• Nutritional Sciences
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• v.5 no.4
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• pp.184-189
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• 2002

The effects of dietary Int levels on lipid metabolism under fixed P/S (1.3) and n-6/n-3 (5.1) fatty acid ratios were examined in rats using palm oil, soybean oil and perilla oil. These ratios correspond to the recommended composition of dietary fat for humans. The range of dietary fat levels was 5-20% by weight (11.8-39.3% of total energy). The levels of dietary fat did not influence the concentrations of serum and liver cholesterol, whereas the level of triglycerides was gradually elevated with increasing levels of dietary fat, especially in the liver. The fatty acid composition of tissue phosphatidylcholine seemed to vary with the different levels of fat. The ratio of linoleic acid to arachidonic acid was increased more significantly in the heart than in the liver. In adipose tissue total lipids, the percentages of saturated and monounsaturated fatty acids decreased, whereas the percentage of polyunsaturated fatty acid increased, with increasing dietary Int levels. In addition, though the level of aortic prostacyclin was not uniformly affected by increasing dietary fat levels, thromboxane A2 production by platelets tended to increase with higher levels of dietary fat, suggesting an increased risk of thrombosis in this situation. Thus, even though dietary fat may have desirable compositions of fatty acids, these excessive consumption can produce unfavorable metabolic responses.

• CELLMED
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• v.4 no.3
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• pp.18.1-18.5
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• 2014

Leea asiatica (L.) Ridsdale, a folk medicinal plant is used by the ethnic people of North East India for the treatment of hepatic disorder. In this study, we have investigated the hepatoprotective and antioxidant activity of L. asiatica leaves against acetaminophen induced hepatotoxicity. Methanol extract of L. asiatica (150 and 300 mg/kg/day, p.o.) were administered to rats for three consecutive days followed by single acetaminophen (3000 mg/kg, p.o.) administration on $3^{rd}$ day. After 48 h of acetaminophen administration animals were sacrificed and biochemical estimation of serum, in vivo antioxidant activity using liver tissue were carried out. High levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, total bilirubin, direct bilirubin, total cholesterol and triglycerides were observed in disease control group, which found near to normal in extract treated groups. Higher dose exhibited significant hepatoprotective activity against acetaminophen induced toxicity. Level of superoxide dismutase, catalase, glutathione peroxidase in liver tissue, and reduced glutathione in liver and blood were also significantly increased in extract (300 mg/kg) treated animals compare to disease control group. In this study we found that leaves of L. asiatica exhibited potent hepatoprotective activity against acetaminophen induced hepatic damage in experimental animals which justify the folklore claim, and the possible mechanism of this activity may be due to strong antioxidant activities of extract.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2563-2569
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• 2012

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.

• Nutrition Research and Practice
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• v.1 no.4
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• pp.247-253
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• 2007

Alpha-tocopherol transfer protein (${\alpha}$-TTP) is a liver cytosolic transport protein that faciliates ${\alpha}$-tocopherol (${\alpha}$-T) transfer into liver secreted plasma lipoproteins. Genetic defects in ${\alpha}$-TTP, like dietary vitamin E deficiency, are associated with infertility, muscular weakness and neurological disorders. Both human and ${\alpha}$-TTP deficient (${\alpha}-TTP^{-/-}$) mice exhibit severe plasma and tissue vitamin E deficiency that can be attenuated by sufficient dietary ${\alpha}$-T supplementations. In this review, we summarize the literature concerning studies utilizing the ${\alpha}-TTP^{-/-}$ mice. Levels of vitamin E in the ${\alpha}-TTP^{-/-}$ mice do not appear to be directly related to the amounts of dietary ${\alpha}$-T or to the levels of ${\alpha}$-TTP protein in tissues. The ${\alpha}-TTP^{-/-}$ mice appear to present a good model for investigating the specific role of ${\alpha}$-T in tissue vitamin E metabolism. Furthermore, ${\alpha}-TTP^{-/-}$ mice appear to be useful to elucidate functions of ${\alpha}$-TTP beyond its well recognized functions of transferring ${\alpha}$-T from liver to plasma lipoprotein fractions.

• Journal of Nutrition and Health
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• v.34 no.7
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• pp.748-753
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• 2001

This study is to investigate the effects of capsaicin with high-fat diet on tissue glycogen contents in exercise-trained rats. Forty male Sprague-Dawley rats were offered a high-fat diet for 2 wks in individual cages and were exercise-trained by a animal treadmill running throughout the experimental period. After 2 wks of the prefeeding with high-fat diet, the rats were divided into two group: high-fat diet group(CON)and high-fat diet + capsaicin(0.014%) group(CAP). The rats were killed by decapitation at 10 hr(rest), 1 hr and 2 hr after treadmill running(27m/min, 6$^{\circ}$). Body weight and epididymal adipose tissure weight were significantly lower in CAP than in CON, but soleus muscle weight was not different between the two groups. Glycogen contents in liver, soleus and gastrocnemius white muscles were significantly lower in CAP than in CON at rest, 1 hr and 2 hr (p<0.05). However, glycogen content in gastrocnemius red muscle was significantly higher in CAP compared with CON at 2 hr after the exercise(p<0.05). These results indicate that capsaicin intake with high-fat diet would decrease glycogen contents in liver and muscle, however, this effect on glycogen metabolism could be changed by muscle type.

• Korean Journal of Veterinary Research
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• v.16 no.1
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• pp.97-103
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• 1976

In order to clarify the histopathological changes resulting from nitrate poisoning, rabbits were experimentally poisoned by the oral administration of $KNO_3$ or $NaNO_2$ and examined clinically and histopathologically. In addition, the quantitative changes of glycogen level in hepatic cells were histochemically observed. The results obtained were summarized as follows: 1. Clinical symptoms observed from the acute cases which died within 2 hours after the administration were severe cyanosis of visible mucosa, frequent urination, and dyspnea. However, in chronic cases administrated daily with $KNO_3$ for 43, 50 and 74 days respectively, no marked symptoms were observed. 2. Macroscopic changes observed in acute cases were severe methemoglobinemia, cloudy swelling of hepatic cells, hemorrhage and hyperemia of gastric mucosa, and hyperemia of other organs. In chronic cases there were marked hyperemia, dark-red coloring and increasing of consistency in liver and kidney, and swelling of spleen. 3. Microscopic changes observed in acute cases were hemorrhage and hyperemia of various organs, cloudy swelling and centrilobular necrosis of hepatic cells and necrosis of convoluted tubular epithelium in kidney. In chronic cases there were round cell infiltration of the interlobular connective tissue and epithelial proliferation of interlobular bile ducts in the liver, and necrosis of the convoluted tubular epithelium and proliferation of interstitial connective tissue in kidney, thickening of alveolar septa of lungs, activated hemopoiesis of bone marrow, and myeloid metaplasia of sqlenic pulp. 4. Glycogen storage in liver cells was decreased in acute cases, on the contrary, increased in chronic cases.

• The Korean Journal of Ecology
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• v.10 no.4
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• pp.205-213
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• 1987

In order to investigate the effects of red ginseng extract to methyl mercury toxicities in mice, the serum lipoproteins, tissure protein patternsm and growth rates were studied. Animals wee divided into 3 groups of the control, group I treated with methyl mercury chloride only, and group II treated together with methyl mercury chloride and red ginseng extract. In serum lipoprotein fractions of group I, beta lipoprotein fraction was increased and pre-beta lipoprotein fraction was decreased in comparision to those of the control. However, there was almost no difference in quantities of serum lipoprotein fractions between the control and group II. Total pretein contents of groups I and II were increased in liver and those of groups I and II in the kidney were decreased. However, in comparison to group I, total protein contents of group II in the liver and kidney were similar values with those of the control. Percentage of tissue protein fractions between control and group I in the liver and kindey showed considerable difference. On the other hand, the percentage of protein fractions of group II approximated to that of the control. Daily average growth rate of body weight in group II was similar to the control, but that of group I was decreased significantly in comparison to the other 2 groups.