Inhibition of 3'-Methyl-4-Dimethylaminoazobenzene-Induced Hepatocarcinogenesis by Portacaval Shunt

1978 ◽  
Vol 64 (2) ◽  
pp. 131-142 ◽  
Author(s):  
Silvio Fiala ◽  
Babulal Pragani ◽  
Melvin D. Reuber
Keyword(s):  
Large Dose ◽  
Gradual Increase ◽  
Portacaval Shunt ◽  
Basal Diet ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Glutamyl Transpeptidase ◽  
Functional Deficiency ◽  
Morphologic Changes ◽  
Intact Rats

Adult male Sprague Dawley rats on which end-to-side portacaval shunt (PCS) operation was performed did not develop hyperplastic nodules and hepatomas when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controls. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24–48 h, compared to the increase of 50–100% in non-operated rats. No clear tendency to a gradual increase in the activity of γ-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5% months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibition of GT-ase increase induced by 3'-Me-DAB in PCS-operated rats contrasted with an increase of GT-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'-Me-DAB-induced hepatocarcinogenesis, manifested by lack of preneoplastic morphologic changes and the absence of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen.

STIMULATION BY OVINE PROLACTIN OF FLUID TRANSFER IN EVERTED SACS OF RAT SMALL INTESTINE

1972 ◽  
Vol 53 (3) ◽  
pp. 453-459 ◽  
Author(s):  
D. H. RAMSEY ◽  
H. A. BERN
Keyword(s):  
Ringer Solution ◽  
Sprague Dawley ◽  
Fluid Uptake ◽  
Sprague Dawley Rats ◽  
Intestinal Segments ◽  
Fluid Transfer ◽  
Ovine Prolactin ◽  
Intact Rats ◽  
Everted Sacs

SUMMARY Ovine prolactin injected subcutaneously for 2 days stimulated an increase in fluid uptake in vitro by everted gut sacs from male Sprague—Dawley rats. Four intestinal segments from each rat were incubated, but only two of the four segments tested showed a prolactin-stimulated increase in fluid transfer in intact rats. In adrenalectomized—nephrectomized rats all four sacs showed an increased fluid transfer after prolactin treatment. Sacs incubated for 1 h in glucose—Ringer solution containing 0·1 mg ovine prolactin/ml did not show an increased water transfer as compared with controls incubated in medium containing albumin. Dietary changes seemed to alter the sensitivity of the gut to prolactin.

Effects of Simultaneous Dietary Exposure to 2,2′,4,4′,5,5′-Hexabromobiphenyl and 3,3′,4,4′,5,5′-Hexachlorobiphenyl on Hepatic Tumor Promotion in Rats

1989 ◽  
Vol 8 (6) ◽  
pp. 1201-1206 ◽  
Author(s):  
M. G. Evans ◽  
S. D. Sleight
Keyword(s):  
Dietary Exposure ◽  
Tumor Promotion ◽  
Inhibitory Effect ◽  
Sprague Dawley ◽  
Gamma Glutamyl Transpeptidase ◽  
Simultaneous Exposure ◽  
Activity Concentrations ◽  
Sprague Dawley Rats ◽  
System Tumor ◽  
Glutamyl Transpeptidase

Female Sprague-Dawley rats were partially hepatectomized, initiated with diethylnitrosamine (DEN), and fed diets containing 2,2′,4,4′,5,5′-hexabromobiphenyl (245-HBB), 3,3′,4,4′,5,5′-hexachlorobiphenyl (345-HCB), or combinations of 245-HBB and 345-HCB to determine the tumor-promoting ability of these compounds in a two-stage (initiation/promotion) hepatocar-cinogenesis system. Tumor-promoting ability was assessed by measuring hepatic foci positive for gamma glutamyl transpeptidase (GGT) activity. Concentrations of 10 or 100 mg 245-HBB/kg of diet caused significantly increased numbers of GGT-positive hepatic foci. When 245-HBB and 345-HCB were fed simultaneously, an additive effect on tumor-promoting ability was observed at dietary concentrations of 10 mg/kg 245-HBB and 0.1 mg/kg 345-HCB. However, an inhibitory effect on tumor promotion occurred when dietary concentrations of 100 mg/kg 245-HBB and 1.0 mg/kg 345-HCB were fed simultaneously. These results suggest that the tumor-promoting ability of simultaneous exposure to 245-HBB and 345-HCB can be additive or inhibitory depending upon the concentration of each congener in the diet.

Phosphaturic effect of L-NMMA in the presence of parathyroid hormone

1996 ◽  
Vol 271 (6) ◽  
pp. R1477-R1480
Author(s):  
M. J. Onsgard-Meyer ◽  
R. J. Kerrigan ◽  
M. Collins ◽  
A. A. Khraibi ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Fractional Excretion ◽  
Parathyroid Glands ◽  
Constant Infusion ◽  
Sprague Dawley ◽  
Phosphate Excretion ◽  
Sprague Dawley Rats ◽  
Additional Group ◽  
Renal Clearances ◽  
Intact Rats

The objective of this study was to examine the effect of NG-monomethyl-L-arginine (L-NMMA) on phosphate excretion in the presence and absence of parathyroid hormone (PTH). Renal clearances were obtained before and during infusion of L-NMMA (15 mg/kg bolus and 500 micrograms.kg-1.min-1 infusion) in Sprague-Dawley rats with intact parathyroid glands (n = 6), in thyroparathyroidectomized (TPTX) rats receiving a constant infusion of PTH-(1-34) (0.01-0.03 U.kg-1.min-1) (n = 11) throughout the experiment, or in TPTX rats, that received an acute infusion of PTH-(1-34) (33 U/kg bolus and 1 U.kg-1.min-1 infusion) after L-NMMA infusion alone (n = 7). In rats with intact parathyroid glands, L-NMMA increased the fractional excretions of phosphate (FEPi) and sodium (FENa) and mean arterial pressure (MAP) (delta 8.6 +/- 1.5%, delta 0.62 +/- 0.1%, and delta 26.7 +/- 4.9 mmHg, respectively; P < 0.05). In TPTX rats receiving a constant infusion of PTH, L-NMMA again increased FEPi, FENa, and MAP (delta 9.5 +/- 3.6%, delta 1.1 +/- 0.4%, and delta 28.4 +/- 4.5 mmHg, respectively; P < 0.05). However, in TPTX rats, L-NMMA alone did not increase FEPi (delta 0.9 +/- 0.3%), whereas the subsequent infusion of PTH with L-NMMA increased FEPi (delta 15.6 +/- 3.1%; P < 0.05). In an additional group of intact and TPTX rats, the fractional excretion of lithium (FELi) was measured as an index of proximal reabsorption. L-NMMA increased FELi in intact rats (delta 13.2 +/- 2.6%; P < 0.05), but not in TPTX rats (delta 4.2 +/- 3.3%). In conclusion, L-NMMA increases phosphate excretion in association with increases in MAP and FENa, and this phosphaturic effect is dependent on the presence of PTH.

scholarly journals Dietary Supplementation with Chitosan Oligosaccharides Alleviates Oxidative Stress in Rats Challenged with Hydrogen Peroxide

Animals ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 55 ◽  
Author(s):  
Ruixia Lan ◽  
Qingqing Chang ◽  
Lilong An ◽  
Zhihui Zhao
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Drinking Water ◽  
Dietary Supplementation ◽  
Basal Diet ◽  
Control Group ◽  
Sprague Dawley ◽  
Antioxidant Power ◽  
Chitosan Oligosaccharides ◽  
Sprague Dawley Rats

Oxidative stress is induced by excessive oxidative radicals, which directly react with biomolecules, and damage lipids, proteins and DNA, leading to cell or organ injury. Supplementation of antioxidants to animals can be an effective way to modulate the antioxidant system. Chitosan oligosaccharides (COS) are the degraded products of chitosan or chitin, which has strong antioxidant, anti-inflammatory, and immune-enhancing competency. Therefore, the current study was conducted to evaluate the hypothesis that dietary supplementation with COS alleviates the damage caused by oxidative stress in Sprague Dawley rats challenged with hydrogen peroxide (H2O2). The rats were randomly divided into three groups: CON, control group, in which rats were fed a basal diet with normal drinking water; AS, H2O2 group, in which rats were fed the basal diet and 0.1% H2O2 in the drinking water; ASC, AS + COS group, in which rats were fed the basal diet with 200 mg/kg COS, and with 0.1% H2O2 in the drinking water. In vitro, COS exhibited better radical scavenging capacity of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion (O2−), H2O2, and ferric ion reducing antioxidant power (FRAP) than butylated hydroxy anisole (BHA). In vivo, dietary supplementation with COS alleviated the H2O2-induced oxidative damage, evidenced by comparatively increasing activity of SOD, CAT, GSH-Px, GSH, and T-AOC, and comparatively decreasing level of MDA in serum, liver, spleen, and kidney. COS also comparatively alleviated the H2O2-induced inflammation. In conclusion, COS supplementation reduced lipid peroxidation and restored antioxidant capacity in Sprague Dawley rats, which were challenged with H2O2.

scholarly journals Suppression of detrusor-sphincter dysynergia by GABA-receptor activation in the lumbosacral spinal cord in spinal cord-injured rats

2008 ◽  
Vol 295 (1) ◽  
pp. R336-R342 ◽  
Author(s):  
Minoru Miyazato ◽  
Kurumi Sasatomi ◽  
Shiro Hiragata ◽  
Kimio Sugaya ◽  
Michael B. Chancellor ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Receptor Activation ◽  
Urethral Pressure ◽  
Sprague Dawley ◽  
Lumbosacral Spinal Cord ◽  
Detrusor Sphincter Dyssynergia ◽  
Sprague Dawley Rats ◽  
Spinal Cord Injured ◽  
Awake Condition ◽  
Intact Rats

We investigated the effects of intrathecal application of GABAA- or GABAB-receptor agonists on detrusor-sphincter dyssynergia (DSD) in spinal cord transection (SCT) rats. Adult female Sprague-Dawley rats were used. At 4 wk after Th9-10 SCT, simultaneous recordings of intravesical pressure and urethral pressure were performed under an awake condition to examine the effect of intrathecal application of GABAA and GABAB agonists (muscimol and baclofen, respectively) or GABAA and GABAB antagonists (bicuculline and saclofen, respectively) at the level of L6-S1 spinal cord. In spinal-intact rats, the effects of bicuculline and saclofen on bladder and urethral activity were also examined. During urethral pressure measurements, DSD characterized by urethral pressure increases during isovolumetric bladder contractions were observed in 95% of SCT rats. However, after intrathecal application of muscimol or baclofen, urethral pressure showed urethral relaxation during isovolumetric bladder contractions. The effective dose to induce inhibition of urethral activity was lower compared with the dose that inhibited bladder contractions. The effect of muscimol and baclofen was antagonized by intrathecal bicuculline and saclofen, respectively. In spinal-intact rats, intrathecal application of bicuculline induced DSD-like changes. These results indicate that GABAA- and GABAB-receptor activation in the spinal cord exerts the inhibitory effects on DSD after SCT. Decreased activation of GABAA receptors due to hypofunction of GABAergic mechanisms in the spinal cord might be responsible, at least in part, for the development of DSD after SCT.

Citrus Pectin and Oligofructose Improve Folate Status and Lower Serum Total Homocysteine in Rats

2003 ◽  
Vol 73 (6) ◽  
pp. 403-409 ◽  
Author(s):  
Thoma ◽  
Green ◽  
Ferguson
Keyword(s):  
Basal Diet ◽  
Sprague Dawley ◽  
Citrus Pectin ◽  
Deficient Diet ◽  
Sulfa Drug ◽  
High Fiber ◽  
Folate Status ◽  
Sprague Dawley Rats ◽  
Increased Risk ◽  
Total Homocysteine

Low folate status leads to increased total homocysteine (tHcy) concentration, and this has been associated with an increased risk of several diseases. Many colonic bacteria are capable of synthesizing folate, and certain dietary fibers may enhance this effect. We assessed the ability of non-fermentable (cellulose) and fermentable (citrus pectin and oligofructose) fibers to improve folate status and lower tHcy in rats. Weanling Sprague-Dawley rats were fed a folate-deficient diet with 5% cellulose for four weeks. Rats were then randomly assigned to one of five folate-adequate (400 mug/kg diet) test diets for 24 days. Diets were as follows: Basal; Basal + Sulfa Drug (succinylsulfathiazole); Cellulose; Citrus Pectin; and Oligofructose. High-fiber diets were formulated by diluting the basal diet such that the final diets contained 10% of the added fiber. Twenty-one days later, 3H-r-aminobenzoic acid was injected into the cecum, and rats were terminated three days later. Rats receiving the Citrus Pectin diet had significantly higher plasma (p = 0.011), erythrocyte (p = 0.035), and colonic tissue folate concentrations (p = 0.013) and lower tHcy (p = 0.003) than rats given the Cellulose diet. Rats receiving the Oligofructose had significantly higher plasma folate (p < 0.001) and lower tHcy (p = 0.032) concentrations than rats receiving the Cellulose diet. 3H-folate was detected in the livers of all rats except those receiving Sulfa Drug. Our study indicates that Citrus Pectin and Oligofructose, but not Cellulose, can significantly increase indices of folate status in rats and lower tHcy. It also confirms the ability of the large bowel to absorb folate.

Inulin/oligofructose and anticancer therapy

2002 ◽  
Vol 87 (S2) ◽  
pp. S283-S286 ◽  
Author(s):  
H. S. Taper ◽  
M. B. Roberfroid
Keyword(s):  
Cancer Treatment ◽  
Malignant Tumors ◽  
Lung Metastases ◽  
Human Cancer ◽  
Dietary Treatment ◽  
Basal Diet ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Interesting Approach ◽  
Cancer Risk Reduction

The results of our investigations indicate that dietary treatment with inulin or oligofructose incorporated in the basal diet for experimental animals: (i) reduced the incidence of mammary tumors induced in Sprague-Dawley rats by methylnitrosourea; (ii) inhibited the growth of transplantable malignant tumors in mice; and (iii) decreased the incidence of lung metastases of a malignant tumor implanted intramuscularily in mice. Moreover, besides such cancer risk reduction effects, the dietary treatment with inulin or oligofructose significantly potentiated the effects of subtherapeutic doses of six different cytotoxic drugs commonly utilized in human cancer treatment. If confirmed, such dietary treatment with inulin or oligofructose potentiating cancer therapy might become an interesting approach to complement classical protocols of human cancer treatment without any additional risk for the patients.

Central angiotensin II-enhanced splenic cytokine gene expression is mediated by the sympathetic nervous system

2005 ◽  
Vol 289 (4) ◽  
pp. H1683-H1691 ◽  
Author(s):  
Chanran K. Ganta ◽  
Ning Lu ◽  
Bryan G. Helwig ◽  
Frank Blecha ◽  
Roman R. Ganta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Sympathetic Nerve ◽  
Gene Array ◽  
Cytokine Gene Expression ◽  
Ang Ii ◽  
Cytokine Gene ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Intact Rats

We tested the hypothesis that central angiotensin II (ANG II) administration would activate splenic sympathetic nerve discharge (SND), which in turn would alter splenic cytokine gene expression. Experiments were completed in sinoaortic nerve-lesioned, urethane-chloralose-anesthetized, splenic nerve-intact (splenic-intact) and splenic nerve-lesioned (splenic-denervated) Sprague-Dawley rats. Splenic cytokine gene expression was determined using gene-array and real-time RT-PCR analyses. Splenic SND was significantly increased after intracerebroventricular administration of ANG II (150 ng/kg, 10 μl), but not artificial cerebrospinal fluid (aCSF). Splenic mRNA expression of IL-1β, IL-6, IL-2, and IL-16 genes was increased in ANG II-treated splenic-intact rats compared with aCSF-treated splenic-intact rats. Splenic IL-1β, IL-2, and IL-6 gene expression responses to ANG II were significantly reduced in splenic-denervated compared with splenic-intact rats. Splenic gene expression responses did not differ significantly in ANG II-treated splenic-denervated and aCSF-treated splenic-intact rats. Splenic blood flow responses to intracerebroventricular ANG II administration did not differ between splenic-intact and splenic-denervated rats. These results provide experimental support for the hypothesis that ANG II modulates the immune system through activation of splenic SND, suggesting a novel relation between ANG II, efferent sympathetic nerve outflow, and splenic cytokine gene expression.

scholarly journals HEPATOPROTECTIVE ACTIVITY OF MERREMIA BORNEENSIS AGAINST CARBON TETRACHLORIDE (CCl4)-INDUCED ACUTE LIVER DAMAGE IN RATS: A BIOCHEMICAL AND HISTOPATHOLOGICAL EVALUATION

2020 ◽  
pp. 41-45
Author(s):  
MOHAMMAD IQBAL ◽  
MUHAMMAD DAWOOD SHAH ◽  
SENTY VUN-SANG ◽  
RIANA BINTI AWANG SAMAN
Keyword(s):  
Lipid Peroxidation ◽  
Carbon Tetrachloride ◽  
Oxidative Damage ◽  
Histopathological Change ◽  
Hepatoprotective Activity ◽  
Quinone Reductase ◽  
Sprague Dawley ◽  
Glutathione S Transferase ◽  
Sprague Dawley Rats ◽  
Glutamyl Transpeptidase

Objective: The pathogenesis of various liver injuries involves oxidative damage. This research was planned to examine the effects of Mereemia borneensis extract on hepatic oxidative damage caused by carbon tetrachloride (CCl4) in rats. Methods: Sprague Dawley rats were exposed to M. borneensis (125 and 250 mg/kg b. wt.) once daily for 14 d followed by two doses of CCl4 (1.2 ml/kg b. wt.). After 2 w, the rats were sacrificed and hepatoprotective analysis was done. Results: Orally administration of CCl4 enhances serum transaminase (ALT; alanine transaminase and AST; aspartate transaminase), γ-glutamyl transpeptidase, lipid peroxidation, reduction in glutathione, catalase, glutathione reductase, glutathione peroxidase, quinone reductase and glutathione S-transferase. Pretreatment of rats with M. borneensis at 125 and 250 mg/kg body weight significantly reduced levels of ALT, AST, γ-glutamyl transpeptidase and lipid peroxidation of CCl4 treated rats. Pretreatment with M. borneensis against rats treated with CCl4, hepatic enzymatic and non-enzymatic antioxidant molecules have increased significantly. A decreased histopathological change in the liver is further evidence of the protective effect of M. borneensis. Conclusion: Our data suggest that M. borneensis can be a potential hepatoprotective agent in preventing or treating degenerative diseases that involve oxidative stress.

scholarly journals Regulation of the renal Na:K pump: role of progesterone.

1993 ◽  
Vol 3 (8) ◽  
pp. 1488-1495
Author(s):  
S K Mujais ◽  
N A Nora ◽  
Y Chen
Keyword(s):  
Inhibitory Effect ◽  
Proximal Convoluted Tubule ◽  
Thick Ascending Limb ◽  
Sprague Dawley ◽  
Medullary Thick Ascending Limb ◽  
Progesterone Treatment ◽  
Sprague Dawley Rats ◽  
High K ◽  
Pump Activity ◽  
Intact Rats

In male Sprague-Dawley rats, the effects of exogenous high physiologic levels of progesterone simulating those observed in pregnancy (5 mg/day) on Na:K pump activity (picomoles per millimeter per hour) in microdissected nephron segments were evaluated. In adrenal-intact rats, progesterone led to a generalized decrease in Na:K pump activity in proximal convoluted tubule from 2,524 +/- 61 to 741 +/- 41 (71% reduction; P < 0.01), medullary thick ascending limb (MAL) from 4,793 +/- 217 to 2,000 +/- 133 (59% reduction; P < 0.01), and cortical collecting tubule (CCT) from 1,141 +/- 69 to 591 +/- 133 (49% reduction; P < 0.01). This effect was similar in magnitude to the decline observed with adrenalectomy alone. In adrenalectomized rats, progesterone had no further inhibitory effect on the pump in MAL (2,172 +/- 66 versus 2,312 +/- 71) or CCT (493 +/- 58 versus 530 +/- 31) but led to a modest decline in Na:K pump activity in the proximal convoluted tubule (from 1,136 +/- 88 to 528 +/- 31; P < 0.01). In adrenal-intact rats, a high K diet for 7 days led to an increase in CCT Na:K pump activity from 1,141 +/- 69 on a normal potassium diet to 2,224 +/- 33 pmol/mm per h (P < 0.001). Progesterone treatment reduced basal Na:K pump activity in CCT, and concurrent progesterone treatment blunted the stimulatory effect of K adaptation on the pump (973 +/- 68 pmol/mm per h; P < 0.001 versus untreated).(ABSTRACT TRUNCATED AT 250 WORDS)

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