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Biomedical subjects

H S Taper

Publications and source records attributed to H S Taper.

At least 19 recordsLinked to original sources
PubMed2002

Inulin and oligofructose modulate lipid metabolism in animals: review of biochemical events and future prospects.

Inulin and oligofructose, besides their effect on the gastro-intestinal tract, are also able to exert 'systemic' effect, namely by modifying the hepatic metabolism of lipids in several animal models. Feeding male Wistar rats on a carbohydrate-rich diet containing 10 % inulin or oligofructose significantly lowers serum triacylglycerol (TAG) and phospholipid concentrations. A lower hepatic lipogenesis, through a coordinate reduction of the activity and mRNA of lipogenic enzymes is a key event in the reduction of very low-density lipoprotein-TAG secretion by oligofructose. Oligofructose is also able to counteract triglyceride metabolism disorder occurring through dietary manipulation in animals, and sometimes independently on lipogenesis modulation: oligofructose reduces post-prandial triglyceridemia by 50 % and avoids the increase in serum free cholesterol level occurring in rats fed a Western-type high fat diet. Oligofructose protects rats against liver TAG accumulation (steatosis) induced by fructose, or occurring in obese Zucker fa/fa rats. The protective effect of dietary inulin and oligofructose on steatosis in animals, would be interesting, if confirmed in humans, since steatosis is one of the most frequent liver disorders, occurring together with the plurimetabolic syndrome, in overweight people. The panel of putative mediators of the systemic effects of inulin and oligofructose consists in either modifications in glucose/insulin homeostasis, the end-products of their colonic fermentation (i.e. propionate) reaching the liver by the portal vein, incretins and/or the availability of other nutrients. The identification of the key mediators of the systemic effects of inulin and oligofructose is the key to identify target function(s) (or dysfunction(s)), and finally individuals who would take an advantage of increasing their dietary intake.

Animals↗
PubMed2002

Inulin/oligofructose and anticancer therapy.

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.

Animals↗
PubMed2002

Potential therapeutic application of the association of vitamins C and K3 in cancer treatment.

The decision of stressed cells to die or to survive is made by integrating signals at different levels through multiple check points. However, initiation and continued progression toward cell death by apoptosis in cancer cells may be blocked by mutation of the tumor suppressor p53 or overexpression of members of the bcl-2 family of proteins. The existence of such mechanisms indicates that cancer cells lose the controls regulating their cell cycle. Therefore, the activation of their programmed cell death appears as a major therapeutic target. Oxidative stress can stimulate growth, trigger apoptosis, or cause necrosis depending upon the dose and the exposure time of the oxidizing agent. A large body of evidence supports the idea that oxidative stress induced by redox cycling of vitamins C and K(3) in association surpasses cancer cellular defense systems and results in cell death. The molecular mechanisms underlying such a process are, however, still unknown. Indeed, several types of cell death may be produced, namely autoschizis, apoptosis and necrosis. Combined vitamin C and K(3) administration in vitro and in vivo produced tumor growth inhibition and increased the life-span of tumor-bearing mice. CK(3)-treatment selectively potentiated tumor chemotherapy, produced sensitization of tumors resistant to some drugs, potentiated cancer radiotherapy and caused inhibition of the development of cancer metastases without inducing toxicity in the host. We propose the association of vitamins C and K(3) as an adjuvant cancer therapy which may be introduced into human cancer therapy without any change in the classical anticancer protocols, and without any supplementary risk for patients.

Animals↗
PubMed2001

Cryopreservation of rat precision-cut liver slices by ultrarapid freezing: influence on phase I and II metabolism and on cell viability upon incubation for 24 hours.

Several cryopreservation methods for precision-cut rat liver slices (PCLS) have been proposed, allowing a short-term (a few hours) maintainance of viability and functionality upon thawing. The aim of the present study was to test the metabolic capacity of PCLS cryopreserved by an ultrarapid method. The biotransformation of paracetamol to its glucuronide and sulfate conjugates and of midazolam to its hydroxylated metabolites was studied in thawed PCLS incubated for 24 hours at 37 degrees C in Williams' medium E. In addition, protein levels of the key enzymes involved in these metabolic reactions, i.e. UGT1A1, ST1A1, CYP2E1 and CYP3A2 were determinated. In addition, biological markers of cell function (ATP and glycogen levels) and toxicity (LDH leakage in the medium) were also measured. Compared to controls (non cryopreserved PCLS), CYP3A2 activity and content and CYP2E1 content were maintained at the same level all along the incubation, whereas paracetamol glucuronidation and sulfation dropped to 24 and 21% of the control value, respectively, immediately after thawing. Freezing-thawing conditions also modified cell functionality, leading to a lower intracellular ATP and glycogen content, and an increase in cell lysis, as shown by LDH released in the medium. The results of this study suggest that cryopreserved PCLS are able to maintain some phase I activities for 24 hours after thawing whereas some phase II metabolic capacities are not maintained.

Acetaminophen↗
PubMed2001

In vivo reactivation of DNases in implanted human prostate tumors after administration of a vitamin C/K(3) combination.

Human prostate cancer cells (DU145) implanted into nude mice are deficient in DNase activity. After administration of a vitamin C/vitamin K(3) combination, both alkaline DNase (DNase I) and acid DNase (DNase II) activities were detected in cryosections with a histochemical lead nitrate technique. Alkaline DNase activity appeared 1 hr after vitamin administration, decreased slightly until 2 hr, and disappeared by 8 hr after treatment. Acid DNase activity appeared 2 hr after vitamin administration, reached its highest levels between 4 and 8 hr, and maintained its activity 24 hr after treatment. Methyl green staining indicated that DNase expression was accompanied by a decrease in DNA content of the tumor cells. Microscopic examination of 1-microm sections of the tumors indicated that DNase reactivation and the subsequent degradation of DNA induced multiple forms of tumor cell death, including apoptosis and necrosis. The primary form of vitamin-induced tumor cell death was autoschizis, which is characterized by membrane damage and the progressive loss of cytoplasm through a series of self-excisions. These self-excisions typically continue until the perikaryon consists of an apparently intact nucleus surrounded by a thin rim of cytoplasm that contains damaged organelles.

Animals↗
PubMed2000

Are Kupffer cells involved in the metabolic adaptation of the liver to dietary carbohydrates given after fasting?

In rats, a high carbohydrate fat-free (HCFF) diet, given after fasting, induces both hepatic lipogenic and glycogenic enzymes. In the present study, we evaluated the involvement of Kupffer cells in the metabolic events occurring in the liver during the fasting-refeeding transition. Male Wistar rats were fasted for 48 h and received an intravenous injection of either NaCl 0.9% (Gd-) or 10 mg/kg GdCl(3) (Gd+), an inhibitor of Kupffer cells, then fed for 12 h with a HCFF diet. The comparison of colloidal carbon uptake was similar in rats fasted and in rats fasted and then refed a HCFF diet, thus indicating that refeeding does not affect per se Kupffer cell phagocytic activity. The inhibition of Kupffer cells by GdCl(3) did not affect fatty acid synthase (FAS) induction, as shown by the analysis of both FAS mRNA and activity; refeeding a HCFF diet increased the hepatic triglyceride and glycogen content to the same extent in Gd+ and Gd- rats. Our results do not support the involvement of Kupffer cells in the metabolic events occurring in the liver tissue by feeding a HCFF diet after fasting. However, the discussion supports the involvement of Kupffer cells in the modulation of the hepatic lipid metabolism by other nutrients than carbohydrates.

Adaptation, Physiological↗
PubMed2000

Dietary oligofructose lessens hepatic steatosis, but does not prevent hypertriglyceridemia in obese zucker rats.

We studied the influence of oligofructose (OFS), a nondigestible fructan, on lipid metabolism in obese fa/fa Zucker rats. The addition of 10 g/100 g OFS to the diet slowed the increase in body weight without modifying serum triglycerides or glucose concentrations after 7 wk of treatment. However, an oral load of 2 g glucose and 5 g corn oil/kg body weight increased triglyceridemia more in OFS-fed rats than in control rats. After 10 wk, OFS decreased the hepatic concentration of triglycerides 57% relative to controls. The less severe steatosis was confirmed by histologic analysis. Among the key enzymes involved in fatty acid synthesis and esterification, only malic enzyme activity was significantly lower in OFS-fed rats than in controls. The epididymal fat mass was significantly lower in OFS-fed rats. In conclusion, dietary enrichment with OFS can counteract both the fat mass development and the hepatic steatosis that occur in obese Zucker rats. Future studies will be designed to clarify in obese animals the influence of dietary OFS on postprandial triglyceridemia, which is an important variable associated with the development of atherosclerosis in humans, and to analyze the biochemical mechanism underlying the "hepatoprotective" effect of OFS.

Analysis of Variance↗
PubMed2000

Apoptosis in renal proximal tubules of rats treated with low doses of aminoglycosides.

Kidney cortex apoptosis was studied with female Wistar rats treated for 10 days with gentamicin and netilmicin at daily doses of 10 or 20 mg/kg of body weight and amikacin or isepamicin at daily doses of 40 mg/kg. Apoptosis was detected and quantitated using cytological (methyl green-pyronine) and immunohistochemical (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) staining, in parallel with a measurement of drug-induced phospholipidosis (cortical phospholipids and phospholipiduria), cortical proliferative response ((3)H incorporation in DNA and histoautoradiography after in vivo pulse-labeling with [(3)H]thymidine), and kidney dysfunction (blood urea nitrogen and creatinine). Gentamicin induced in proximal tubules a marked apoptotic reaction which (i) was detectable after 4 days of treatment but was most conspicuous after 10 days, (ii) was dose dependent, (iii) occurred in the absence of necrosis, and (iv) was nonlinearly correlated with the proliferative response (tubular and peritubular cells). Comparative studies revealed a parallelism among the extents of phospholipidosis, apoptosis, and proliferative response for three aminoglycosides (gentamicin >> amikacin congruent with isepamicin). By contrast, netilmicin induced a marked phospholipidosis but a moderate apoptosis and proliferative response. We conclude that rats treated with gentamicin develop an apoptotic process as part of the various cortical alterations induced by this antibiotic at low doses. Netilmicin, and still more amikacin and isepamicin, appears safer in this respect. Whereas a relation between aminoglycoside-induced tubular apoptosis and cortical proliferative response seems to be established, no simple correlation with phospholipidosis can be drawn.

Amikacin↗
PubMed2000

Nontoxic potentiation of cancer chemotherapy by dietary oligofructose or inulin.

Our previously published results indicated that dietary treatment with oligofructose or inulin inhibited malignant tumor growth in experimental animals. Thus it appeared to be interesting to investigate whether the same treatment could have a positive influence on tumor chemotherapy. The chemotherapy-potentiating effect of 15% oligofructose or inulin incorporated into the basal diet for experimental animals was investigated on a transplantable mouse liver tumor. This dietary adjuvant therapy was started seven days before intraperitoneal transplantation of transplantable liver tumor and was continued until the end of experiments. A single, subtherapeutic dose of six different cytotoxic drugs commonly utilized in treatment of human cancer was intraperitoneally injected 48 hours after tumor transplantation. In all experiments, dietary oligofructose or inulin significantly potentiated the therapeutic effects of six different cytotoxic drugs. Such dietary treatment potentiating cancer chemotherapy could be introduced into classical protocols of human cancer treatment as a new, nontoxic, and easily applicable adjuvant cancer therapy without any supplementary risk for patients.

Animal Feed↗
PubMed1999

Modulation of paracetamol metabolism by Kupffer cells: a study on rat liver slices.

Recent studies support the hypothesis that non parenchymal cells (mainly macrophages) may play a role in the metabolism and cellular effects of paracetamol. In order to investigate this hypothesis, male Wistar rats were intravenously injected with either 7.5 mg/kg gadolinium chloride (Gd+) or NaCl 0.9% (Gd-). The treatment with GdCl3 decreased the number and the function of Kupffer cells in liver tissue, as assessed by the histological examination of the liver after colloidal carbon injection in the portal vein. Precision-cut liver slices (PCLS) were prepared from both groups of rats and cultured for 8h in Waymouth's medium in the presence and absence of 5 mM paracetamol. Interestingly, PCLS obtained from Gd+ rats exhibited a lower release of tumor necrosis factor (TNF-alpha) and a better viability than PCLS from control (Gd-) rats. Incubation with paracetamol led to a decreased glycogen level in liver slices from Gd+ or Gd-, without modifying neither liver morphology nor ATP level nor LDH release. A higher proportion of paracetamol glucuronide, was secreted from the slices obtained from Gd+ rats. These data suggest that Kupffer cells could affect the viability of PCLS in culture and are involved in the regulation of phase II metabolism in the adjacent hepatocytes. We propose that PCLS in culture is a suitable model to elucidate the biochemical mechanism underlying the modulation of metabolism occurring through hepatocytes-Kupffer cells interactions.

Acetaminophen↗
PubMed1999

Influence of inulin and oligofructose on breast cancer and tumor growth.

Because anticarcinogenic and tumor-growth-inhibiting effects of nonsoluble fibers have been described, similar actions of soluble fibers appear to merit investigation. In a preliminary study on methylnitrosourea-induced mammary carcinogenesis in Sprague-Dawley female rats, 15% oligofructose added to the basal diet modulated this carcinogenesis in a negative manner. There was a lower number of tumor-bearing rats and a lower total number of mammary tumors in oligofructose-fed rats than in the group fed the basal diet alone. The effect of dietary nondigestible carbohydrates (15% oligofructose, inulin or pectin incorporated into the basal diet) on the growth of intramuscularly transplanted mouse tumors, belonging to two tumor lines (TLT and EMT6), was also investigated. The results were evaluated by regular tumor measurements with a vernier caliper. The mean tumor surface in the experimental groups was compared with that in animals of the control group fed the basal diet containing starch as the only carbohydrate. The growth of both tumor lines was significantly inhibited by supplementing the diet with nondigestible carbohydrates. Such nontoxic dietary treatment appears to be easy and risk free for patients, applicable as an adjuvant factor in the classical protocols of human cancer therapy.

Adenocarcinoma↗
PubMed1998

Lack of protective effect of menhaden oil supplementation on rat liver steatosis induced by a carbohydrate-rich diet.

Liver steatosis is often attributed to dietary habits. Our previous results have shown that fatty acid synthesis is considerably increased by high carbohydrates-fat free diet (HCFF) given to rats after fasting, and leads to lipid accumulation and morphological alterations in the liver, defined as steatosis. As n-3 polyunsaturated fatty acids are able to counteract lipogenesis induction in vivo and in vitro, we hypothesized that the addition of menhaden oil in a carbohydrate-rich diet might be able to protect the liver against steatosis induced by a fasting-re-feeding transition. Male Wistar rats were first fasted for 48 hr, then re-fed ad lib. for 24 hr with either (1) standard diet; (2) high carbohydrates-fat free diet (HCFF), containing 40% (w/w) starch, 40% saccharose, 16% casein and 4% vitamin mineral mix; or (3) the latter diet containing additionally 5% menhaden oil (HCMO) for 24 hr. Triglyceride (TG) accumulation occurred in liver tissue of rats re-fed with HCFF and HCMO diets after fasting. The addition of menhaden oil led to a strong decrease in serum TG; however, both TG and phospholipid (PL) levels, as well as fatty acid synthase activity, were increased in the liver of HCMO rats as compared with the values obtained in HCFF re-fed rats. Histologically diagnosed steatosis was even more severe when rats received HCMO than HCFF. These results indicate that menhaden oil supplementation does not avoid, but even increases, the degree of steatosis generated in vivo by re-feeding a high carbohydrate diet after fasting.

Animals↗
PubMed1997

Growth inhibition of transplantable mouse tumors by non-digestible carbohydrates.

The possible influence of dietary non-digestible carbohydrates (15% oligofructose, inulin or pectin incorporated in basal diet) on the growth of intramuscularily transplanted mouse tumors, from 2 tumor lines (TLT and EMT6), was investigated. The results were evaluated by regular tumor measurements with Vernier caliper. Mean tumor surface in experimental groups was compared with that in animals of control group fed basal diet containing starch as the only carbohydrate. The growth of both tumor lines was significantly inhibited by supplementation of non-digestible carbohydrates.

Animals↗
PubMed1997

A new model of acute liver steatosis induced in rats by fasting followed by refeeding a high carbohydrate-fat free diet. Biochemical and morphological analysis.

BACKGROUND/AIMS: Dietary habits are often considered to be responsible for fatty liver, a common histological finding in human liver biopsies. The aim of the present work was to test the hypothesis that fasting followed by refeeding high carbohydrate-fat free diets in rats disrupts hepatic lipid homeostasis, leading to liver lipid accumulation and morphological alterations. METHODS: Male Wistar rats were fasted for 48 h, then refed ad libitum with a high carbohydrate-fat free diet. RESULTS: Six hours after refeeding, a slight microvacuolar steatosis, mainly located in zone I was observed, whereas later on in the process, macrovacuolar steatosis extended to all three zones of the hepatic lobules. The present paper also contributes information on the mechanism of fasting-high carbohydrate-fat free diet, diet-induced steatosis: we show that both circulating and de novo hepatic synthesized fatty acid availabilities are implicated in the disequilibrium between triglyceride synthesis and secretion. CONCLUSIONS: The results are discussed, taking into account the putative implication of carbohydrate-induced lipogenesis in human fatty liver, occurring in non-insulin-dependent diabetic or obese patients.

Acute Disease↗
PubMed1995

Protective effect of dietary fructo-oligosaccharide in young rats against exocrine pancreas atrophy induced by high fructose and partial copper deficiency.

The objective of this investigation was to protect rats against exocrine pancreatic atrophy by adding 22% fructo-oligosaccharide (FOS), a natural fructan obtained from inulin, to the 50% copper-deficient diets containing qualitatively and quantitatively different carbohydrates. Young male Wistar rats were maintained on these diets for 10 wk, being weighed weekly then killed and autopsied. Major organs were weighed and histologically examined. Copper content in the diets was measured by flame atomic absorption spectroscopy. Incomplete (50%) copper deficiency avoided precocious mortality due to cardiovascular lesions and enabled another pathological condition to develop, consisting of the induction of exocrine pancreas atrophy. Introduction of gradually increasing percentages of fructose in diets at the level of 22, 42 and 62% induced a gradual increase in the copper-deficiency-mediated pathology in rats, expressed by an increase in exocrine pancreatic atrophy. 22% FOS introduced to the diet prevented the pathology induced by both fructose and partial copper deficiency better than starch added to diet at the level of 20 or 40%.

Animals↗
PubMed1994

Modifications of liver bile acids pool during modulation of rat hepatocarcinogenesis by phenobarbital and nafenopin.

As previously demonstrated, chronic administration of phenobarbital (0.05% in the drinking water) and of nafenopin (0.1% in the diet) increases the incidence and the kinetics of appearance of liver cancers. If bile acids play a key role in liver carcinogenesis, it might thus be expected that treatments like phenobarbital or nafenopin, which positively modulate that process, also modify their hepatic pool. The aim of the present study was to analyze the modifications of the liver bile acid pool during the modulation of liver carcinogenesis by phenobarbital and nafenopin. The animals were submitted to the hepatocarcinogenic initiation-selection (IS) procedure adapted from Solt and Farber. As compared to basal diet, the chronic feeding of phenobarbital significantly increased the total concentrations of liver bile acids both at weeks 9 and 17. That increase was mainly due to a change in the concentration of beta-muricholic acid and hyodeoxycholic acid and, to a lesser extent, of chenodeoxycholic acid and alpha-muricholic acid. In contrast, feeding a diet containing nafenopin led to a significant decrease in the concentration of liver bile acids, due to a complete disappearance of chenodeoxycholic acid and muricholic acid, and a decrease in the concentration of hyodeoxycholic acid. Carcinomas appearing in IS phenobarbital-treated rats contain fewer bile acids than the surrounding parenchyma (because of the decrease in deoxycholic acid and ursodeoxycholic acid) whereas the malignant tumors appearing in IS nafenopin-treated rats have essentially the same pattern of bile acids as the surrounding parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Changes in bile acids metabolism during rat hepatocarcinogenesis: causative or unrelated?

In the present paper, we have aimed at studying the variations in the metabolism of bile acids occurring during an hepatocarcinogenic process induced in male Wistar Rats by the biphasic protocol of Solt and Farber. Bile acids concentrations was measured in the liver. The most significant changes have been observed 5 weeks after the beginning of the treatment, it means one week after the selection treatment consisting in 2-acetylaminofluorene administration: the increase in cholic acid, and of its intestinal metabolite, deoxycholic acid, and of alpha- and beta- muricholic acids, are likely to be a consequence of an acute effect of 2-acetylaminofluorene. To test for the putative implication of liver bile acids modifications in the selection effect of 2-acetylaminofluorene, diethyl-nitrosamine-pretreated rats were fed a diet containing 1% lithocholic acid, a treatment that induces essentially the same qualitative changes in liver bile acids, as 2-acetylaminofluorene does: no selection effect of lithocholic acid could be demonstrated. These results suggest that changes in bile acid metabolism occurring early in hepatocarcinogenesis are more likely to be secondary than causative events. The same conclusion comes from the results obtained later on in the process, where there is only a high increase in liver cholic acid and deoxycholic acid concentrations.

2-Acetylaminofluorene↗