The distribution, metabolism and excretion of CKD-602{20(S)-7-[2-(N-Isopropylamino)ethyl]camptothecin HCI), a new camptothecin derivative, were investigated in rats after a sing le administration of CKD-602. 1. The tissue levels of CKD-602 given to mice by the intravenous route at a dose of 20mg/kg were the highest in intestine, followed in descending order by kidney, liver, stomach,lung, heart, spleen and plasma. The concentrations of CKD-602 after 24hrs decreased to less than 2% of the peak level in most tissues except the skin. The urinary and fecal excretion of CKD-602 were 47.6% and 44.4% of the administered dose, respectively, with 0.7% remaining in the rinse. 2. After administration of CKD-602 at 10mg/kg in rats, metabolism of this compound was examined in plasma, urine, and feces. The plasma samples were collected for 24hr, urinary and fecal samples for 72hr. While any peak of CKD-602 in HPLC chromatograms was not detected from plasma and urine it was detected in feces (peaks, 9.8 min). However, additional peak area was about 0.5% of the peak area of parent CKD-602. Therefore, CKD-602 may be eliminated with the parent form and rarely metabolized in the body. 4. After I.v. administration of CKD-602 at 10mg/kg in rats, urinary and fecal excretions were examined for 72hrs post dose period. 87% of total urinary excretion of CKD-602 was excreted within 8hr after administration, 53%, and 32% of total fecal excreted amounts were determined in 0-24 hr and 24-48hr periods, respectively. The total excretion amounts of CKD-602 into urine and feces were 94% of the administered dose.
Journal of Physiology & Pathology in Korean Medicine
/
v.25
no.6
/
pp.989-995
/
2011
Hypothyroidism is the most common disease in the endocrine system. Cistanche Deserticola has been used traditionally in the treatment of kidney deficiency and Yang deficiency syndrome. In this study, we investigated the therapeutic effects of Cistanche Deserticola on Hypothyroidism rat model induced by PTU. 24 Two-month-old Sprague-Dawley male rats were divided into 4 groups : 1) normal(n=6), 2) PTU-induced hypothyroidism control(n=6), 3) hypothyroidism rat treated with Cistanche Deserticola(n=6), 4) hypothyroidism rat treated with levothyroxine(n=6). PTU was administered for 4 weeks. Cistanche Deserticola and levothyroxine was administered 2 weeks after PTU was initiated for a total duration of 2 week. Body weights were checked every week and after 4 weeks, biochemical analysis was performed and T3, T4 and TSH were measured by ELISA kits. In comparison with the normal group, the control group showed hypothyroidism with lower T3, T4 level and higher TSH level. In the Cistanche group the level of T4 was significantly increased and TSH level was significantly decreased. There was no significant difference in biochemical labs and weight between the Cistanche group and the control group. These findings suggest that Cistanche Deserticola could help the production of thyroid hormones under PTU suppression. And there is no harmful effect on liver and kidney function, and other metabolism. According to these results Cistanche Deserticola could be an useful agent for treating hypothyroidism.
For toxicity model in the kidney, renal cell carcinoma (RCC) is one of the most important model to assess the structural and functional alterations. Most RCCs are sporadic, and environmental agents are suspected to play a role in the etiology of the disease. In this study, we discovered novel evidence for previously unknown gene expression patterns related to progression according to cancer stage in RCC. Four clear cell RCC tissue samples along with five corresponding patient-matched normal kidney tissue samples were obtained from patients undergoing partial or radical nephrectomy. To examine the difference of gene expression profile in clear cell RCC, radioactive cDNA microarrays were used to evaluate changes in the expression of 1,152 genes in a total. Using $^{33}P-labeled$ probes, this method provided highly sensitive gene expression profiles including drug metabolism, and cellular signaling. 29 genes were identified with expression levels that differed by more than 2.0 value of z-ratio, compared with that in control. Whereas expression of 38 genes were decreased by less than-2.0 value of z-ratio. In conclusion, this study has identified 67 gene expression alterations in clear-cell type of RCC. Most notably, genes involved in cell growth were up-regulated in stage I more than stage III whereas genes involved in signal transduction were down-regulated in which both stage I and stage III. The identified alteraions of gene expression will likely give in sight in to clear cell RCC and tumor progression.
Journal of Physiology & Pathology in Korean Medicine
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v.27
no.2
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pp.212-224
/
2013
This study intends to clarify how Sayeok-tang(here in after reffered to SYT) affect C57BL/10 mice whose osteoarthritis was induced by papain. Osteoarthritis was induced by injecting papain in the knee joint of 3 groups(n=6) of mice. Normal group was non-treatment group and was not injected papain, whereas control mice were orally administered with $200{\mu}{\ell}$ of physiological saline. Positive comparison group was medicated with 100 mg/kg of Joins$^{(R)}$ mixed with $200{\mu}{\ell}$ of physiological saline. Experimental group was medicated with 400 mg/kg of SYT mixed with $200{\mu}{\ell}$ of physiological saline. Both Positive and experimental comparison groups were orally medicated once per day for 4 weeks. After the experiment, the functions of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological changes in the knee joint structures were observed. As results, SYT had no significant effect on the liver and kidney functions. Interleukin-$1{\beta}$(IL-$1{\beta}$), interleukin-6(IL-6), monocyte chemo attractant protein-1(MCP-1) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) were significantly decreased. Inflammation cytokines in joints were all significantly decreased. Prostaglandin $E_2(PGE_2)$, thromboxane $B_2(TXB_2)$ were significantly decreased. Destruction of cartilage on micro computed tomography(CT)-arthrography was meaningfully decreased. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small. Based on all results mentioned above, Sayeok-tang(SYT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.
High-fructose corn syrup (HFCS) is widely used as sweetener, and its overconsumption is become a major health problem. In the present study, we used adult female rats and applied a 28 days HFCS feeding model to monitor the estrous cycle and changes in tissue weights and histology. Adult female rats were divided into three groups. Animals were fed with ad libitum normal chow and (1) 24 hours tap water (Control group), (2) 12 hours HFCS access during dark period and 12 hours tap water (12H group), and (3) 24 hours HFCS only access (24H group). Total exposure period was 28 days. There is no significant change in body weight between control and HFCS-fed animals. Both absolute and relative weights of ovary in 24H animals were significantly heavier than those in control or 12H animals. The absolute and relative weights of the kidney and liver in 24H groups were significantly heavier than those in control or 12H animals. The estrous cycles of the 24H animals were significantly longer. Histological analyses revealed that 24H ovaries were relatively bigger and possessed more corpus lutea than control ovaries. Uterine sections of 12H and 24H animals showed a well-developed stratum vasculare between inner and outer myometrial layers. The number of endometrial glands were decreased in 12H uteri, and recovered in 24H uteri compared to control. Numbers of convoluted tubule in distal region increased in 12H and 24H kidney samples. Liver specimens of 12H and 24H showed the increased number of fat containing vacuoles. In conclusion, our study demonstrated that HFCS treatment for 28 days could induce (1) changes in length of estrous cycle with extended estrous and diestrous stages, (2) altered ovarian and uterine histology, and (3) liver and renal lipid accumulation. These findings reveal the adverse effects of HFCS drinking on the reproductive function and lipid metabolism of female rats.
Background: Bone fractures are high in elderly patients with type 2 diabetes mellitus (T2DM). Hyperglycemia and chronic kidney disease may increase the risk of fracture prevalence via altered bone metabolism, but whether glycemic control and kidney function are associated with the risk of fracture prevalence remains unclear. This study evaluated the relationship between glycemic control and baseline estimated glomerular filtration rate (eGFR) and risk of fracture prevalence in older and middle-aged patients with T2DM. Methods: Patients who underwent a general medical check-up between 2009 and 2013 were selected from the Korean National Health Insurance Sharing Service records. Chi-square test and multiple logistic regression analysis were used to assess the relationship between glycemic control and eGFR and risk of fracture prevalence. Results: Cumulative fracture prevalence were higher in patients with T2DM, irrespective of whether they had tight or less stringent glycemic control (fasting blood glucose [FBG] ${\geq}110mg/dL$). After adjustment for baseline age and FBG, tight and less stringent glycemic control was significantly associated with increased adjusted risk of fracture prevalence in middle-aged patients with T2DM (OR=1.13, 95% CI, 1.05-1.21, p=0.0005 vs OR=1.13, 95% CI, 1.06-1.20, p=0.0001), but not in older patients. Baseline eGFR was not significantly related to fracture prevalence in either older or middle-aged patients. Conclusion: Less stringent glycemic control significantly increased the adjusted risk of fracture prevalence in middle-aged patients with T2DM. Further studies are needed to confirm the effect of tight glycemic control on fracture prevalence.
This study investigated the effects of chitosan on cadmium(Cd) toxicity and mineral metabolism in rats exposed to cadmium by oral administration. Six week-old Sprague-Dawley rats were divided into eight groups. Four groups were fed AIN-93G based 3% ${\alpha}$-cellulose diets while the others were fed 3% chitosan diets for four weeks with oral administration of 0, 0.5, 1.0, 2.0 mg Cd/2ml distilled water three times a week, respectively. Cd contents in the serum, liver, kidney, testis and bone, and the excretion of cadmium in feces were determined. There was no significant difference in weight gain and food intake among groups. Cadmium contents in the serum, liver, kidney, testis, femur and lumbar were significantly increased in proportion to the administration level of Cd (p<0.05). A protective effect of chitosan on cadmium toxicity in tissue was shown only in the high level cadmium-intake group. The fecal excretion, absorption of Cd were increased by the administration levels of cadmium. These results suggest that Cd administration may facilitate the accumulation of Cd in the blood and tissue in proportion to the amount of administration, and also, that chitosan may be effective in lowering the accumulation of cadmium.
This study was performed to investigate nutritional effect of various dietary fibers on lead absorption and metabolism of protein and lipid in growing rats. Forty eight male rats of Sprague-Dawley strain weighing 75.7$\pm$0.7g were blocked into six groups according to body weight and fed six kinds of diet different with fiber source(non-fiber, cellulose, pectin) and lead level(0%, 1% ) for 4 weeks. Results are summerized as follows: 1) Food intake, weight gain, FER and PER were remarkably decreased in lead(Pb) added groups, and FER and PER in Pb-added pectin group were significantly lower than those in Pb-added non-fiber group. 2) Weight of liver, kidney and epididymal fat pad, bone weight and length, hematocrit, and hemoglobin content were decreased in Pb-added groups. 3) Total protein content in serum was tended to be decreased in Pb-added groups, but total lipid and cholesterol contents in serum were not different with dietary Pb level and fiber source. 4) Nitrogen, lipid and cholesterol content in liver were tended to be deceased in Pb-added groups, and especially those of the Pb-added pectin group were the lowest among groups. 5) Daily urinary and fecal excretions of nitrogen, lipid and cholesterol were decreased in Pb-added groups. Especially fecal excretions of nitrogen, lipid and cholesterol in Pb-free groups were significantly increased by dietary cellulose and pectin. 6) Pb content in blood was significantly increased in Pb-added pectin group. There was no significant decrease in Pb contents of liver, kidney and tibia, and increase in excretion of Pb by feeding dietary fibers. In conculsion, dietary fibers had no effect on the absorption of Pb, and dietary pectin seemed to increase Pb poisoning by decreasing bioavailibility of protein, lipid and other nutrients in the diet.
Misaengtang (MST), a formula of Korean herbal medicines, has been used as a weight-controlling recipe. We have investigated two experiment of body weight regulation by MST In rats. i) The anti-obesity effect of MTS on a high fat diet-induced obesity, male Sprague-Dawley rats were fed with a high-fat diet containing 30% in the absence or presence of MST (0.3, 1 or 3%) or a reference orlistat (0.05%) for 6 weeks. ii) weight-decrease effect of MST on normal diet, same animal were fed with a normal diet in the absence or presence of MST (3%) for 6 weeks. And the body weights, daily feed and water consumptions, organ weights, fat weights serum biochemistry were measured. In both experiments, MST and orlistat did not affect the body weight gain. But orlistat significantly increased the feed and water consumptions, leading to low-feed efficiency, and orlistat markedly reduced abdominal, paratesticular and perirenal fat weights, although increased the kidney weights. In MST, low dose (0.3%) of MST decreased the perirenal fat and increased the kidney weights in rats fed HFD, and MST 3% decreased the abdominal fat weights in rats fed normal diet. In addition, Orlistat caused changes in parameters of hepatotoxicity (AST and glucose), nephrotoxicity (BUN and B/C ratio) and lipid metabolism (HDL and triglycerides). In comparison, MST decreased AST, ALP and ALT, the hepatotoxicity markers, and somewhat improved the hepatic fatty degeneration. Taken together, it is suggested that MST does not exert anti-obesity activity as well as remarkably direct effects, but MST may be potentially benefit for dietary cure and exercise-cure of obesity.
Three kinds of Korean food (Ramyon, bread and dried Injulmi, a kind of rice bread) and basal diet were fed to ten groups of rat with consideration of their basal metabolism and some physiological changes were checked for four months. And obtained results were as follows: 1. In the rate of growth (body weight), rats fed on combined basal diet with Ramyon (20% or 33%) were slightly superior to those of simple basal diet (control case), and rats fed simply on Ramyon, bread or Injulmi were all inferior to the control. 2. Throughout the experiment, no considerable changes in intestinal bacterial flora, liver function and kidney function were observed in all cases, as compared with the control. 3. Liver tissues and kidney tissues in all cases were identified as normal and same as those of the control.
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