kaolinite and Body-Weight

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (eight animals per group): Group 1: Normal control (saline i.p.). Group 2: Rats received cyclophosphamide (200 mg/kg i.p.) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg i.p.) across Days 1-7, and C. sativa (20 and 40 mg/kg s.c.) was administered on cyclophosphamide days 4-7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5-HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestinal homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5-HT, dopamine and noradrenaline, as well as decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa also improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.

Topics: Animals; Antineoplastic Agents; Antioxidants; Body Weight; Cannabis; Cyclophosphamide; Dopamine; Humans; Kaolin; Nausea; Norepinephrine; Rats; Rats, Wistar; Serotonin

The effects of cyclophosphamide on 5-hydroxytryptamine (5-HT) synthesis in the intestinal tissue of rats were investigated. Rats received 120 mg/kg cyclophosphamide intraperitoneally as a single administration, and kaolin and food intake was measured by an automatic monitoring apparatus. Ileal tissues were collected at either 24 or 72 h after administration. Cyclophosphamide caused a significant increase in kaolin intake at the acute and the delayed phases and was associated with a decrease in food intake, and body weight. Cyclophosphamide had no significant effect on intestinal mucosal morphology, or inducible nitric oxide synthase and cyclooxygenase-2 expression in the intestine. Cyclophosphamide significantly increased tryptophan hydroxylase 1 (TPH1) mRNA expression, number of anti-TPH antibody-positive cells, and 5-HT content in the intestine. Cyclophosphamide also significantly increased the expression of Tac1 mRNA, encoding preprotachykinin-1, which is a preprotein of substance P, and the number of anti-substance P antibody-positive cells in the intestine. Cyclophosphamide significantly increased Lgr5, Bmi1, and Atoh1 mRNA levels, which are markers for the proliferation and differentiation of stem cells. This study demonstrated that cyclophosphamide induced pica in rats, and potentiated 5-HT synthesis associated with hyperplasia of substance P-containing enterochromaffin cells without causing severe intestinal injury.

Topics: Animals; Antineoplastic Agents, Alkylating; Body Weight; Cyclophosphamide; Eating; Enterochromaffin Cells; Hyperplasia; Infusions, Parenteral; Intestines; Kaolin; Male; Pica; Rats, Wistar; Serotonin; Substance P; Tryptophan Hydroxylase

Some local communities in Cote d'Ivoire use the mushroom Termitomyces schimperi combined with kaolin (TSK) to manage various cancers in patients. However, there is a paucity of data on toxicity, mutagenicity and trace metal constituent of TSK.. We sought to investigate the acute and sub-chronic toxicities, mutagenic potential, and trace metal constituents of TSK.. To assess acute toxicity, single doses (1000, 3000 and 5000 mg/kg) of aqueous extract of TSK were administrated per os to Sprague Dawley (SD) rats on Day 1. The rats were then monitored for 13 consecutive days. Sub-chronic toxicity was evaluated by daily administration of 200 and 500 mg/kg of the extract per os for 90 consecutive days. SD rats used as control received distilled water. Signs of toxicity, changes in body weight and mortality were monitored. After the aforementioned monitoring processes, rats were sacrificed and blood collected for full blood count and biochemistry analysis. Animal organs were also collected for histopathological examination. The mutagenic potential of the aqueous extract of TSK (10000 μg/mL) on TA98 Salmonella typhimurium was estimated. Additionally, energy-dispersive X-ray fluorescence (ED-XRF) method was employed to determine trace metal constituents of TSK.. The aqueous extract of TSK showed no toxicity (acute and sub-chronic) at doses tested. These findings are consistent with the absence of heavy metals (i.e., cadmium) and potentially toxic elements (i.e., uranium) in TSK samples analysed. TSK showed some level of mutagenic potential. Further mutagenic and chronic toxicity studies on TSK are required.

Topics: Animals; Body Weight; Cote d'Ivoire; Heart; Kaolin; Kidney; Lethal Dose 50; Liver; Lung; Male; Medicine, African Traditional; Mutagenicity Tests; Myocardium; Neoplasms; Organ Size; Plant Extracts; Rats, Sprague-Dawley; Salmonella typhimurium; Spleen; Termitomyces; Time Factors; Toxicity Tests, Subchronic; Trace Elements

Kaolin clay eating has been considered as a marker of nausea in rats, because a variety of treatments, which evoke nausea in humans, generate consumption of kaolin clay in rats. The present study with two experiments replicated kaolin clay ingestion induced by an injection of emetic lithium chloride (LiCl). The LiCl injection, however, did not generate eating of wooden objects in rats. The present study also provides a new finding that consumption of kaolin clay alleviates rats' taste aversion learning caused by an LiCl injection. This finding is congruent with the contention that consumption of kaolin clay is not only a useful index of, but also an effective remedy for, drug-induced nausea in rats.

Topics: Analysis of Variance; Animals; Antidiarrheals; Antimanic Agents; Avoidance Learning; Body Weight; Eating; Kaolin; Lithium Chloride; Male; Nausea; Rats; Rats, Wistar; Taste

Memantine is a selective, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that has previously been shown to have neuroprotective qualities in some animal models of neurologic disease. We hypothesized that memantine therapy would improve behavioral, neuropathological, and/or biochemical outcomes in juvenile rats with kaolin-induced hydrocephalus. Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna. Magnetic resonance imaging was performed one week later to assess ventricle size and stratify rats to three treatment groups. Rats were blindly treated daily for three weeks with saline or 10 or 30 mg/kg/day memantine. Behavior measures were performed weekly. Histologic and biochemical evaluations were performed at termination. Hydrocephalic rats showed no differences in weight among treatment groups. Memantine treatment stabilized ventricular enlargement in both low and high dose groups. The high dose group exhibited increased motor activity in open field chambers compared to the vehicle-treated group. However, there were no significant differences between the three hydrocephalic treatment groups for other behavioral tasks. Ventriculomegaly was associated with periventricular white matter damage. Glial fibrillary acidic protein (GFAP) content was higher in the low dose memantine group compared to vehicle-treated group, but there were no differences in GFAP-immunoreactive astrocytes or Iba-1- immunoreactive microglia between groups. Memantine therapy stabilized ventricular expansion and improved some behavioral measures but did not reduce brain tissue changes in juvenile rats with kaolin-induced hydrocephalus.

Topics: Animals; Body Weight; Cerebral Ventricles; Disease Models, Animal; Excitatory Amino Acid Antagonists; Female; Hydrocephalus; Kaolin; Male; Memantine; Motor Activity; Neuroprotective Agents; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate; Single-Blind Method; White Matter

We investigated the possible neuroprotective effects of the free radical scavenger edaravone in experimental hydrocephalus.. Seven-day-old Wistar rats were divided into three groups: control group (C), untreated hydrocephalic (H), and hydrocephalic treated with edaravone (EH). The H and EH groups were subjected to hydrocephalus induction by 20% kaolin intracisternal injection. The edaravone (20 mg/kg) was administered daily for 14 days from the induction of hydrocephalus. All animals were daily weighed and submitted to behavioral test and assessment by magnetic resonance imaging. After 14 days, the animals were sacrificed and the brain was removed for histological, immunohistochemical, and biochemical studies.. The gain weight was similar between groups from the ninth post-induction day. The open field test performance of EH group was better (p < 0.05) as compared to untreated hydrocephalic animals. Hydrocephalic animals (H and EH) showed ventricular ratio values were higher (p < 0.05), whereas magnetization transfer values were lower (p < 0.05), as compared to control animals. Astrocyte activity (glial fibrillary acidic protein) and apoptotic cells (caspase-3) of EH group were decreased on the corpus callosum (p > 0.01), germinal matrix (p > 0.05), and cerebral cortex (p > 0.05), as compared to H group.. We have demonstrated that administration of edaravone for 14 consecutive days after induction of hydrocephalus reduced astrocyte activity and that it has some beneficial effects over apoptotic cell death.

Topics: Animals; Antidiarrheals; Antipyrine; Apoptosis; Body Weight; Caspase 3; Disease Models, Animal; Edaravone; Exploratory Behavior; Free Radical Scavengers; Glial Fibrillary Acidic Protein; Gliosis; Hydrocephalus; In Situ Nick-End Labeling; Kaolin; Magnetic Resonance Imaging; Male; Neuroglia; Phosphopyruvate Hydratase; Rats; Rats, Wistar

Araniella cucurbitina (Araneae: Araneidae) is a widespread orb-weaver spider commonly found in agroecosystems. Mineral particle films such as kaolin, due to their protective or anti-feeding action, can represent an alternative to pesticides, especially in organic farming systems, but little is known about its effects on A. cucurbitina. Therefore, we tested the effect of kaolin sprays on the life span of A. cucurbitina under laboratory conditions. Four treatments were tested encompassing different exposure routes. Thus, kaolin sprays were applied on (i) the surface, (ii) the prey (fly), (iii) the spider and (iv) both spider & prey. A control group was tested with water in each treatment. Results showed that sprays of kaolin significantly affected the survival of A. curcubitina when applications were done on the surface and on both spider & prey registering a reduction of 48% and 56%, respectively. Spiders in control obtained higher probability of reaching alive at the end of the assay than those treated with kaolin. Differences observed can be explained by the feeding behavior of the species and may depend on the consumption of the web by the spider and the ratio spider/fly for body size.

Topics: Animals; Body Weight; Feeding Behavior; Female; Insect Control; Kaolin; Kaplan-Meier Estimate; Longevity; Male; Pesticides; Spiders

The effects of methotrexate on 5-hydroxytryptamine (5-HT) metabolism in the intestinal tissue of rats were investigated during the delayed phase after a single administration. Rats were i.p. injected with methotrexate or with saline as a control, and kaolin and food intakes were measured by an automatic monitoring apparatus. At 96 h after administration, dissected-out ileal tissue was frozen rapidly in liquid nitrogen for further analysis or fixed for immunohistochemical staining. Methotrexate at a dose of 50 mg/kg caused a time-dependent increase in kaolin intake lasting up to 72 h after administration, which returned to the control level at 96 h after administration. This dose of methotrexate caused a gradual decrease in body weight, food intake, and water intake lasting up to 72 h, which approached the control level at 96 h. Methotrexate caused pathologic changes, including a moderate inflammatory response in the ileal tissue and an increase in the number of L-tryptophan hydroxylase (TPH)-expressing cells in the ileal mucosa. Methotrexate also caused a significant increase in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content and in TPH1 mRNA expression in the ileal tissues. It had no significant effects on mRNA expression of serotonin transporter, COX-1, or COX-2 or on myeloperoxidase activity. This study demonstrated, for the first time, that methotrexate caused a change in the ileal 5-HT metabolism associated with hyperplasia of mucosal enterochromaffin cells.

Topics: Animals; Body Weight; Cyclooxygenase 1; Cyclooxygenase 2; Eating; Hydroxyindoleacetic Acid; Ileum; Kaolin; Male; Membrane Proteins; Methotrexate; Peroxidase; Rats, Wistar; RNA-Binding Proteins; RNA, Messenger; Serotonin; Tryptophan Hydroxylase

Nausea and vomiting are considered as the foremost unpleasant side effects of chemotherapy experienced by 20-90% of cancer patients.. In the present study, the effects of Korean Panax ginseng C.A. Meyer (Araliaceae) (RG), ginseng saponin (GS) and non-saponin (GNS) on cisplatin (CP)-induced pica and gastric damage in rats were investigated.. Rats were treated with RG (25, 50, 100 mg/kg b.wt.), GS (5 and 10 mg/kg 100 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) before or after a single intraperitoneal injection of CP (6 mg/kg b.wt.). Kaolin together with normal food intake, normal food alone, body weight, histological examination of stomach and small intestine were used as indices of CP-induced pica in rats.. Pre-treatment with RG (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake at 24 h. CP-induced kaolin intake decreased upon post-treatment of rats with RG (50 and 100 mg/kg b.wt.) at 48 h. The incidence of body weight reduction at 48 and 72 h diminished in rats post-treated with RG (50 mg/kg b.wt.). Pre-treatment with GS (5 and 10 mg/kg b.wt.) and GNS (50 and 100 mg/kg b.wt.) attenuated CP-induced kaolin intake while normal food intake was not improved in 24 and 48 h.. The gastro-protective effects of RG, GS and GNS were further confirmed by histopathological (damage in glandular portion and villi with dilated appearance) findings. The study indicates that both the red GS and GNS improve feeding behavior against CP-induced pica in rats.

Topics: Animals; Antineoplastic Agents; Body Weight; Cisplatin; Disease Models, Animal; Dose-Response Relationship, Drug; Eating; Injections, Intraperitoneal; Intestine, Small; Kaolin; Male; Panax; Pica; Plant Extracts; Rats; Rats, Sprague-Dawley; Saponins; Stomach; Time Factors

Clay consumption is a spontaneous behavior currently observed in animals and humans, particularly during undernutrition. Often regarded as intestinal care products, ingested clays also enhance food efficiency, notably by increasing intestinal lipid uptake. Clay complementation could then optimize the reconstitution of energy reserves in animals with low lipid stocks consecutive to intensive fasting. The aim of this study was therefore to observe the effects of voluntarily kaolinite complementation during the refeeding of fasted rats to determine whether body mass, food uptake, lipid and mineral contents as intestinal morphology and protein profile were modified. This study examined two types of refeeding experiments after prolonged fasting. Firstly, rats with ad libitum access to food were compared to rats with ad libitum access to food and kaolinite pellets. Animals were randomly put into the different groups when the third phase of fasting (phase III) reached by each individual was detected. In a second set of experiments, rats starting phase III were refed with free access to food and kaolinite pellets. When animals had regained their body mass prior to fasting, they were euthanized for chemical, morphological, and proteomic analyses. Although kaolinite ingestion did not change the time needed for regaining prefasting body mass, daily food ingestion was seen to decrease by 6.8% compared with normally refed rats, without affecting lipid composition. Along the intestinal lining, enterocytes of complemented animals contained abundant lipid droplets and a structural modification of the brushborder was observed. Moreover, the expression of two apolipoproteins involved in lipid transport and satiety (ApoA-I and ApoA-IV) increased in complemented rats. These results suggest that kaolinite complementation favors intestinal nutrient absorption during refeeding despite reduced food uptake. Within the intestinal lumen, clay particles could increase the passive absorption capacity and/or nutrient availability that induce mucosal morphological changes. Therefore, clay ingestion appears to be beneficial for individuals undergoing extreme nutritional conditions such as refeeding and limited food supplies.

Topics: Animals; Apolipoprotein A-I; Apolipoproteins A; Body Weight; Eating; Energy Metabolism; Enterocytes; Fasting; Intestinal Absorption; Intestinal Mucosa; Kaolin; Lipid Metabolism; Male; Microvilli; Rats; Rats, Wistar; Time Factors

Panax ginseng is an indigenous medicinal herb and has traditionally been used among Asian population for relief of many human ailments. We investigated the prophylactic role of Korean P. ginseng extract (KG) against X-ray irradiation-induced emesis in an acute rat pica model. Rats were treated with KG (12.5, 25, 50 mg/kg orally at -48, -24 and 0 h) prior to X-ray irradiation (6 Gy), and intake of kaolin and normal food and body weight changes examined as an index of the acute emetic stimulus. Levels of serotonin in small intestine tissue were assessed and histopathology of gastric tissue, small intestine and colon examined specific staining. Pre-treatment with KG (12.5 and 25 mg/kg) reduced X-ray irradiation-induced kaolin intake at 24h. Normal food intake was improved in rats treated with 25 mg/kg KG. The anti-emetic effect of KG was further confirmed on the basis of serotonin release, histopathological findings. Our findings collectively indicate that KG protects against X-ray irradiation-induced acute pica to a moderate extent, leading to improved feeding behavior in rats.

Topics: Animals; Body Weight; Colon; Energy Intake; Feeding Behavior; Ginsenosides; Intestine, Small; Kaolin; Male; Panax; Phytotherapy; Pica; Plant Extracts; Rats; Rats, Sprague-Dawley; Serotonin; Stomach; Vomiting; X-Rays

It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

Topics: Animals; Antineoplastic Agents, Alkylating; Body Weight; Cyclophosphamide; Eating; Hydroxyindoleacetic Acid; Kaolin; Male; Ondansetron; Pica; Rats; Rats, Inbred F344; Rats, Long-Evans; Rats, Sprague-Dawley; Rats, Wistar; Serotonin Antagonists

Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK(1) receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT(3) receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK(1) receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.

Topics: Animals; Antineoplastic Agents; Aprepitant; Biological Transport; Body Weight; Cisplatin; Dexamethasone; Eating; Kaolin; Male; Morpholines; Ondansetron; Pyridines; Pyrimidinones; Rats; Substance P

To evaluate the effect of Armillariella tabescens on cisplatin chemotherapy-induced gastrointestinal tract reaction.. Forty-eight male Sprague-Dawley rats were randomized into control group, model group, low dose Armillariella tabescens group, middle dose Armillariella tabescens group, high dose Armillariella tabescens group and ondansetron group. The rats were injected intraperitoneally with cisplatin to induce pica, and observe the effect of Armillariella tabescens on consumption of kaolin, food, water and body weight.. 24-72 h after cisplatin administration, in the middle dose Armillariella tabescens group, the high dose Armillariella tabescens group and the ondansetron group, the kaolin intake was significantly lower than that in the model group, respectively (P<0.05). The most significant difference was between the high dose Armillariella tabescens group [(0.58 +/- 0.23) g/24 h] and the control group [(2.16 +/- 0.98) g/24 h] at 24 h after cisplatin administration. The variables, such as consumption of food during 48-72 h (P<0.05), water during 48-72 h (P<0.05), and body weight at 72 h (P<0.05) in the middle dose Armillariella tabescens group were significantly higher than those in the model group, but no statistically significant difference between the ondansetron group and the model group (P>0.05).. Armillariella tabescens can effectively inhibit the cisplatin-induced pica response, and the middle dose Armillariella tabescens group is significantly better than the model group in improving the food intake reduction, water intake reduction and body weight loss.

Topics: Agaricales; Animals; Antiemetics; Antineoplastic Agents; Biological Therapy; Body Weight; Cisplatin; Drinking; Eating; Kaolin; Male; Ondansetron; Pica; Random Allocation; Rats; Rats, Sprague-Dawley

Clay consumption can occur during illness but there has been little work to understand why. To investigate whether consuming clay confers an advantage to the sick animal, we compared the recovery from illness of adult male rats with or without access to kaolin. Illness was induced by injection of 6 mg/kg, ip, cisplatin, a toxic chemotherapy agent, and recovery was assessed by changes in daily food intake, water intake, and body weight. Relative to saline-injected controls, cisplatin-injected rats reduced food and water intake and lost weight. However, those with access to kaolin ate more food and lost less body weight than did those without access to kaolin. Thus, clay consumption appeared beneficial in that it either protected the rats from illness or enhanced recovery and might prove useful as an adjunct therapy for other animals, including humans, experiencing visceral malaise.

Topics: Animals; Body Weight; Cisplatin; Drinking; Drug Interactions; Eating; Kaolin; Male; Pica; Rats; Rats, Sprague-Dawley

Hydrocephalus is a common neurological problem in humans, usually caused by an impairment of cerebrospinal fluid (CSF) flow or absorption. A reliable induced model of chronic hydrocephalus in mice would be useful to test hypotheses using genetic mutants. Our goal was to characterize behavioral and histological changes in juvenile and young adult mice with kaolin (aluminum silicate)-induced hydrocephalus. Seven-day old and 7-8 week old mice received injection of kaolin into the cisterna magna. Behavior was assessed repeatedly. Seven or 14 days following kaolin, magnetic resonance (MR) imaging was used to assess ventricle size. In hydrocephalic mice, body weight was significantly lower than in age-matched saline-injected sham controls and the gait and posture score were impaired. Juvenile mice developed severe ventriculomegaly and had reduced corpus callosum thickness with gross white matter destruction by 14 days. Reactive astroglial change in white matter and cortex and reduced cellular proliferation in the subependymal zone were also apparent. Young adult mice developed only moderate ventricular enlargement without overt white matter destruction, although there was corpus callosum atrophy and mild astroglial reaction in white matter. Glial fibrillary acidic protein content was significantly higher in juvenile and young adult hydrocephalic mice at 7 and 14 days, but myelin basic protein content was not significantly altered. In conclusion, hydrocephalus induced by percutaneous injection of kaolin in juvenile and young adult mice is feasible. The associated periventricular alterations are essentially the same as those reported in rats of comparable ages.

Topics: Aging; Animals; Animals, Newborn; Antidiarrheals; Astrocytes; Body Weight; Brain; Cerebral Cortex; Corpus Callosum; Disease Models, Animal; Glial Fibrillary Acidic Protein; Gliosis; Hydrocephalus; Injections, Intraventricular; Kaolin; Lateral Ventricles; Magnetic Resonance Imaging; Male; Mice

Anticancer agents, such as cisplatin, induce vomiting, nausea, and anorexia. Cisplatin primarily acts on vagal afferents to produce emesis, but little is known about how this drug generates nausea and anorexia. Electrophysiology indicates that cisplatin activates vagal afferents of the common hepatic branch (CHB). Rats lack an emetic response but do ingest kaolin clay (a pica response) when made sick by toxins, and this behavior can be inhibited by antiemetic drugs. It has been postulated that pica may serve as a proxy for emesis in the rat. The goal of this study was to assess the effect of CHB or ventral gastric (Gas) or celiac (Cel) branch vagotomies on pica and anorexia produced by cisplatin in the rat. The effects of apomorphine, a dopamine receptor agonist, which induces emesis via a central mechanism, were also assessed. Cisplatin-induced pica was suppressed by CHB vagotomy (a 61% reduction) but not by Gas and Cel vagotomy. Suppression of daily food intake and body weight following cisplatin treatment was also blunted by CHB ablation but not by Gas or Cel vagotomy. No vagotomy condition exhibited altered apomorphine-induced pica. The results indicate that the CHB, which innervates primarily the duodenum, plays an important role in cisplatin-induced malaise. These data suggest that pica has sensory pathways similar to emetic systems, since a vagotomy condition inhibited cisplatin-induced pica but had no effect on apomorphine-induced pica. This investigation contributes to the delineation of the physiology of pica and neural systems involved in malaise in the nonvomiting rat.

Topics: Animals; Anorexia; Antineoplastic Agents; Apomorphine; Body Weight; Celiac Plexus; Cisplatin; Dopamine Agonists; Drinking; Eating; Kaolin; Liver; Male; Pica; Rats; Rats, Sprague-Dawley; Stomach; Vagotomy; Vomiting

Anorexia, nausea/emesis and peripheral sensorial neuropathy are frequent adverse effects associated with chemotherapy. Cannabinoids have been proposed to alleviate these effects, but their preventive properties in long-term experimental models have not been tested. This study was conducted to determine whether or not a cannabinoid agonist (WIN-55,212-2) can prevent anorexia, pica (an indirect marker of nausea in non-vomiting species, consisting of the ingestion of non-nutritive substances such as kaolin) and mechanical allodynia (a marker of peripheral neuropathy) induced by the antineoplastic drug cisplatin chronically administered. Isolated rats with free access to food and kaolin received either saline, cannabinoid vehicle, WIN-55,212-2 (1-2 mg kg(-1)), cisplatin (1-2 mg kg(-1)), or both drugs once per week for five consecutive weeks. Modifications in temperature, body weight gain, food and kaolin intake, and the threshold for mechanical allodynia were recorded. Additionally, the acute psychoactive effects of the cannabinoid (hypomotility, hypothermia, analgesia and catalepsia) were assayed by means of the cannabinoid tetrad. WIN 55,212-2 prevented the development of mechanical allodynia but not anorexia, pica and reduction in weight gain induced by chronic cisplatin. The effect of WIN 55,212-2 was evident even at a dose lacking activity in the cannabinoid tetrad. The preventive effect on cisplatin-induced mechanical allodynia exerted by the cannabinoid could be due to a neuroprotective role, as has been suggested for other conditions. The present results support the interest in the evaluation of cannabinoids for treatment of patients suffering or likely to suffer neuropathic pain.

Topics: Analgesics; Animals; Antidiarrheals; Antineoplastic Agents; Benzoxazines; Body Temperature; Body Weight; Cisplatin; Feeding Behavior; Kaolin; Male; Morpholines; Naphthalenes; Pain; Peripheral Nervous System Diseases; Pica; Rats; Rats, Wistar

The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4-11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3-300 microg.kg(-1).day(-1)) dose dependently reduced food intake and body weight gain (ED(50) for body weight gain = 16.5 microg.kg(-1).day(-1)). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 microg.kg(-1).day(-1)) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 microg.kg(-1).day(-1)) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.

Topics: Amyloid; Animals; Body Weight; Diet; Dietary Fats; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Food Preferences; Islet Amyloid Polypeptide; Kaolin; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Satiety Response; Weight Gain

In an observational study using heparinase-modified thrombelastography, we investigated the percentage of elective cardiothoracic surgical patients receiving low-dose unfractionated heparin (5000 IU 12 hourly subcutaneously) who had a demonstrable systemic heparin effect. Blood samples were obtained at induction from 40 adult elective cardiothoracic surgical patients who had received 5000 IU unfractionated heparin subcutaneously within six hours. Simultaneous kaolin and heparinase-modified thrombelastographies were run on all samples. Fourteen patients (35%; 95% CI: 20 to 50%) had a demonstrable heparin effect (defined as a kaolin thrombelastography R time >25% longer than the heparinase-modified control). Their mean +/- SD kaolin thrombelastography R time was 13.6 +/- 5.9 minutes (normal range 4 to 8 minutes) vs. 7.1 +/- 2.0 minutes for the heparinase-modified controls. In 10 patients the thrombelastography R times were >50% longer and in four patients >100% longer than their respective heparinase-modified controls. In a post hoc analysis, there was little correlation between the extent of the prolongation and patient age (r = 0.02), weight (r = -0.31), preoperative creatinine (r = -0.17), or time since administration of heparin (r = 0.14). These results indicate that about one third of patients who have received low-dose unfractionated heparin subcutaneously within six hours have a demonstrable heparin effect. The potential for this effect should be considered if central neural blockade is planned.

Topics: Adult; Aged; Anticoagulants; Body Weight; Creatinine; Dose-Response Relationship, Drug; Elective Surgical Procedures; Female; Heparin Lyase; Heparin, Low-Molecular-Weight; Humans; Kaolin; Male; Middle Aged; Thoracic Surgical Procedures; Thrombelastography; Time Factors

Exenatide (exendin-4) is an incretin mimetic currently marketed as an antidiabetic agent for patients with type 2 diabetes. In preclinical models, a reduction in body weight has also been shown in low-fat-fed, leptin receptor-deficient rodents.. To more closely model the polygenic and environmental state of human obesity, we characterized the effect of exenatide on food intake and body weight in high-fat-fed, normal (those with an intact leptin signaling system) rodents. As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity.. High-fat-fed C57BL/6 mice and Sprague-Dawley rats were treated with exenatide (3, 10 and 30 microg/kg/day) for 4 weeks via subcutaneously implanted osmotic pumps. Food intake and body weight were assessed weekly. At 4 weeks, body composition and plasma metabolic profiles were measured. Kaolin consumption and locomotor activity were measured in fasted Sprague-Dawley rats following a single intraperitoneal injection of exenatide (0.1-10 microg/kg). Exenatide treatment in mice and rats dose-dependently decreased food intake and body weight; significant reductions in body weight gain were observed throughout treatment at 10 and 30 microg/kg/day (P<0.05). Decreased body weight gain was associated with a significant decrease in fat mass (P<0.05) with sparing of lean tissue. Plasma cholesterol, triglycerides and insulin were also significantly reduced (P<0.05). Exenatide at 10 microg/kg significantly reduced food intake (P<0.05) but failed to induce kaolin intake. In general, locomotor activity was reduced at doses of exenatide that decreased food intake, although a slightly higher dose was required to produce significant changes in activity.. Systemic exenatide reduces body weight gain in normal, high-fat-fed rodents, a model that parallels human genetic variation and food consumption patterns, and may play a role in metabolic pathways mediating food intake.

Topics: Animals; Body Composition; Body Weight; Diabetes Mellitus, Type 2; Eating; Exenatide; Female; Hypoglycemic Agents; Kaolin; Male; Mice; Mice, Inbred C57BL; Motor Activity; Obesity; Peptides; Rats; Rats, Sprague-Dawley; Venoms

In animals without the emetic reflex, several emetogenic stimuli induce pica, an altered feeding behaviour consisting of the ingestion of non-nutritive substances. The development of pica in response to an emetogenic stimulus has been proposed to be useful as an indirect marker of nausea in the rat. In fact, like nausea and emesis in humans, it is accompanied by serotonin release from the enterochromaffin cells, increased c-fos labelling in the area postrema and the nucleus tractus solitarius, and a delay in gastric emptying. Furthermore, pica, measured as kaolin intake, is reduced by anti-emetic drugs. Pica has been demonstrated after single doses of cisplatin, the most emetogenic chemotherapeutic drug. However, cisplatin, as other antineoplastic drugs, is generally given in cycles, where conventional anti-emetics tend to lose efficiency. The aim of this work was to evaluate the pica induced by long-term treatment with cisplatin. Saline or cisplatin was administered once a week for 5 consecutive weeks, and temperature, body weight, food ingestion and kaolin intake were measured on a daily basis. The influence of isolation (pica is necessarily studied in isolated animals) and exposure to kaolin (basal kaolin intake could modify pica itself and other parameters) on temperature, body weight and daily food ingestion was negligible in saline-treated rats. Cisplatin administered at 3 mg/kg/week was too toxic: it produced hypothermia, weight drop and anorexia in both grouped and isolated rats, and 50% mortality in isolated animals. Toxicity associated with cisplatin administered at 1 mg/kg/week was acceptable, with a slower rate of weight gain being the major effect. In these rats, each cisplatin injection produced both acute anorexia and rebound hyperphagic responses. In addition, each administration induced both acute pica and an increase in basal kaolin intake, resembling the development of nausea in humans. This model could be useful for studying both the mechanisms leading to nausea associated with a long-term antineoplastic treatment and the efficiency of new anti-emetic drugs.

Topics: Animals; Antineoplastic Agents; Behavior, Animal; Body Temperature; Body Weight; Cisplatin; Drug Administration Schedule; Feeding Behavior; Kaolin; Male; Rats; Rats, Wistar; Social Isolation; Time Factors

Neonatal and congenital hydrocephalus are common problems in humans. Hydrocephalus was induced in 1-day-old rats by injection of kaolin into the cisterna magna. At 7 and 21 days, magnetic resonance (MR) imaging was used to assess ventricle size, then brains were subjected to histopathological and biochemical analyses. Hydrocephalic pups did not exhibit delays in righting or negative geotaxis reflexes during the first week. At 7 days, there was variable ventricular enlargement with periventricular white matter edema, axon damage, reactive astrogliosis, and accumulation of macrophages in severe but not mild hydrocephalus. Cellular proliferation in the subependymal zone was significantly reduced. The cortical subplate neuron layer was disrupted. In rats allowed to survive to 21 days, weight was significantly lower in severely hydrocephalic rats. They also exhibited impaired memory in the Morris water maze test. Despite abnormal posture, there was minimal quantitative impairment of walking ability on a rotating cylinder. At 21 days, histological studies showed reduced corpus callosum thickness, fewer mature oligodendrocytes, damaged axons, and astroglial/microglial reaction. Reduced myelin basic protein, increased glial fibrillary acidic protein, and stable synaptophysin content were demonstrated by immunochemical methods. In conclusion, impairment in cognition and motor skills corresponds to ventricular enlargement and white matter destruction. Quantitative measures of weight, memory, ventricle size, and myelin, and glial proteins in this neonatal model of hydrocephalus will be useful tools for assessment of experimental therapeutic interventions.

Topics: Age Factors; Animals; Animals, Newborn; Antidiarrheals; Behavior, Animal; Blotting, Western; Body Weight; Brain Injuries; Cerebral Ventricles; Enzyme-Linked Immunosorbent Assay; Hydrocephalus; Immunohistochemistry; Kaolin; Ki-67 Antigen; Magnetic Resonance Imaging; Myelin Basic Protein; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Time Factors; Walking

Rats lack the emetic reflex but exhibit pica in response to stimuli that induce emesis in species with an emetic reflex, hence it has been proposed that pica may be analogous to emesis in species lacking the reflex. In the present study, we investigated whether pica was present in Suncus murinus (with an emetic reflex) as well as in rats and mice (without emetic reflex) to provide a further insight to the validity of pica as a model for nausea/vomiting. Cisplatin (6 mg/kg, i.p.) induced pica in rats, indicated by a significant increase in kaolin consumption at 24 h (but not 48 h) post-treatment whereas we failed to demonstrate this effect in mice (inbred or outbred strain, 6 or 20 mg/kg i.p.) and whilst cisplatin (20 mg/kg, i.p.) induced emesis in Suncus, kaolin intake was not significantly affected. Furthermore, cisplatin significantly increased the weight of gastric contents at 48 h post-injection in rats and mice indicating delayed gastric emptying whereas this effect was not present in Suncus. These results show that Suncus and two strains of mice, unlike rats, do not develop pica in response to cisplatin which suggests that the consumption of kaolin induced by cisplatin may not be associated with whether or not an emetic reflex is present. The differences in ingestive behaviour and gastric response between species with and without an emetic reflex in response to cisplatin treatment as well as the difference between mice and rats, is discussed in relation to the selection of models for the study of nausea and vomiting.

Topics: Animals; Body Weight; Cisplatin; Disease Models, Animal; Drinking; Eating; Kaolin; Male; Mice; Nausea; Organ Size; Pica; Rats; Shrews; Species Specificity; Stomach; Time Factors

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent known anorexigens with an unestablished mechanism of action. In the present study, the role of nausea in TCDD-induced hypophagia was assessed by a battery of behavioral (conditioned taste aversion [CTA], kaolin consumption, protein selection), biochemical (plasma oxytocin), and antiemetic drug intervention (trimethobenzamine, metoclopramide) approaches. Moreover, both the most TCDD-susceptible (Long-Evans [L-E]; IP LD50 approximately 10 micrograms/kg) and the most TCDD-resistant (Han/Wistar [H/W]; IP LD50 > 3000 micrograms/kg) rat strains were employed in the experiments. L-E rats were exposed to a lethal dose of TCDD (50 micrograms/kg), whereas H/W rats were treated with high but nonlethal doses (50 or 1000 micrograms/kg). TCDD produced a positive CTA response in H/W rats alone. These animals also increased their kaolin consumption more than L-E rats of either gender after TCDD exposure. TCDD decreased the proportional intake of energy from high-protein diet in female L-E rats, but tended to increase it in male L-E and H/W rats. TCDD did not affect plasma oxytocin concentration by itself, but potentiated the elevation caused by the positive control compound, LiCl, in L-E rats on day 8. Neither antiemetic tested had any detectable influence on TCDD-induced wasting. These findings imply that the degree of nausea elicited by TCDD in the rat depends on strain and gender. However, nausea has only a minor, if at all, causal role in the lethal wasting syndrome characteristic of this compound.

Topics: Animals; Antiemetics; Benzamides; Body Weight; Eating; Energy Metabolism; Female; Kaolin; Male; Metoclopramide; Nausea; Oxytocin; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains; Rats, Wistar; Taste

Experimental pleurisy was induced by intrapleural injection of carrageenin or kaolin in three strains of rat: Brown Norway-Katholiek (B/N-Ka), Brown Norway-Kitasato (B/N-Ki) and Sprague-Dawley (SD). B/N-Ka rats (kininogen-deficient) showed significantly less pleural fluid accumulation and exudation rate than SD rats or than B/N-Ki rats (normal). The result indicates the involvement of the plasma kallikrein-kinin system in these pleurisies and a role of high-molecular-weight kininogen is suggested.

Topics: Acute Disease; Aging; Animals; Body Weight; Carrageenan; Inflammation; Kallikreins; Kaolin; Kininogens; Kinins; Organ Size; Pleurisy; Rats; Rats, Inbred Strains; Species Specificity; Tetradecanoylphorbol Acetate

The ability of adult Brown Leghorn cockerels to regulate food intake precisely was tested by measuring their responses to dietary dilutions with 100, 200, 300 and 400 g kaolin per kg diet. When changed from their original undiluted mash diet, cockerels continued gaining body weight with 100 and 200 g kaolin/kg dilutions, maintained weight with 300 g/kg and lost weight continuously with 400 g/kg. With all dilutions, the birds eventually adjusted weights of dry matter digested per day to the same levels as with the original basal diet. This took a few days with 100 g kaolin/kg, a week or more with 200 and 300 g/kg, and about three weeks with 400 g/kg. They achieved this mainly by increasing consumption of diluted food to maintain their original intake of basal diet. With 400 g kaolin/kg they were unable to compensate fully in amount eaten, but digestibility of the basal diet increased significantly. It is suggested that, given the right conditions, fowls may be able to compensate accurately when challenged with a range of dietary dilutions, the upper limit depending on the density of filler used.

Topics: Animals; Body Weight; Chickens; Digestion; Eating; Energy Metabolism; Food Additives; Kaolin; Male

Topics: Animals; Body Weight; Feeding Behavior; Female; Food; Kaolin; Lithium; Nutritive Value; Quinine; Rats

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Diet; Dietary Carbohydrates; Eating; Feeding Behavior; Female; Food Preferences; Hypothalamus; Kaolin; Obesity; Rats; Saccharin; Taste

Topics: Age Factors; Animals; Blood Glucose; Body Weight; Diet; Feeding Behavior; Female; Food Deprivation; Glucose; Kaolin; Male; Milk; Rats; Time Factors; Water

Topics: Age Factors; Aluminum; Analysis of Variance; Animal Feed; Animals; Body Weight; Cellulose; Diet; Feces; Female; Kaolin; Male; Metabolism; Nutritional Physiological Phenomena; Oxides; Rats; Silicon Dioxide; Time Factors; Water

Topics: Adipose Tissue; Animals; Body Temperature Regulation; Body Weight; Diet; Feedback; Feeding Behavior; Female; Growth; Hormones; Hypothalamus; Kaolin; Male; Rats

Topics: Animals; Body Weight; Diet; Glucose; Growth; Intestinal Absorption; Intestine, Large; Intestine, Small; Intestines; Kaolin; Organ Size; Rats; Water