PubMed Health⌕ Search

Biomedical subjects

P Piyachaturawat

Publications and source records attributed to P Piyachaturawat.

At least 19 recordsLinked to original sources

Choleretic activity of phloracetophenone in rats: structure-function studies using acetophenone analogues.

The relationship between the chemical structure and choleretic activity of phloracetophenone (2,4,6-trihydroxyacetophenone) was investigated in adult male rats. Fourteen acetophenone analogues, with different substituents on the benzene nucleus, were intraduodenally administered and bile samples were collected via a bile fistula. All of the compounds tested immediately induced choleresis. For the same number of substituents on the benzene ring, hydroxy analogues induced a greater choleresis. The number and position of hydroxy substituents on the benzene nucleus play an important role in determining choleretic activity and biliary secretion of bile acid, but had no relation to biliary excretion of cholesterol. The choleretic activity of the hydroxylated compounds was inversely related to hydrophobicity, as inferred by thin-layer chromatography (TLC). Among the hydroxylated acetophenone analogues, 2,4,6-trihydroxyacetophenone was identified as the most potent, with a choleretic activity of 231.8+/-6.1 microl/mmol/min. It induced both a high bile flow rate and a high bile salt output and led to lower plasma cholesterol levels. This bile had a low lithogenic potential. The results suggest that a structural requirement for high choleretic activity of 2,4,6-trihydroxyacetophenone is a substituent hydroxy group at 4-position. Additional hydroxy groups at 2- and 6-positions are essential for the induction of higher an output of bile acid, and possibly, other solid materials.

Acetophenones↗

Reduction of plasma cholesterol by Curcuma comosa extract in hypercholesterolaemic hamsters.

The influence of the extract of Curcuma comosa Roxb. (Zingiberaceae) on lipid metabolism was investigated in hypercholesterolaemic hamsters. Intragastric administration of the ethyl acetate extract of C. comosa rhizome (0-500 mg/kg per day) to hypercholesterolaemic animals for 7 days decreased both plasma triglyceride and cholesterol levels in a dose-dependent manner. The reduction of plasma cholesterol levels was accompanied by a significant increase in the hepatic cholesterol content while the triglyceride content was not significantly changed. The increase of the hepatic cholesterol content was brought about by an expansion of the free cholesterol pool which specifically augments biliary cholesterol excretion. The C. comosa extract also increased plasma high density lipoprotein (HDL)-cholesterol and decreased plasma low density lipoprotein (LDL)-cholesterol. These results suggest that the C. comosa extract exerts a hypolipidaemic action by acceleration of lipid mobilization from extrahepatic tissue to the liver which subsequently increases excretion of cholesterol via the bile for excretion.

Animals↗

Effect of chronic K+ deficiency on contractile properties of soleus muscle in rats: evidence of sex differences.

1. Alterations in skeletal muscle function of chronically K(+)-depleted male and female rats were investigated in isolated soleus muscles. 2. By 16 weeks K+ deficiency, plasma K+ concentrations in both male and female rats were reduced to approximately 2 mEq/L, which was accompanied by an approximate 50% reduction in muscle K+ content and a marked increase in muscle Na+ content. These changes were similar in both males and females. 3. Plasma creatine phosphokinase activity progressively increased with time in K(+)-depleted male rats, whereas only a slight increase was observed in female rats. 4. Maximum isometric twitch tension (Pt) and tetanic tension (Po) of K(+)-depleted soleus muscles from male rats was markedly suppressed; this was not seen for soleus muscles obtained from female rats. 5. After exposure to insulin in low-K+ solution, the contractile tension of soleus from the K(+)-depleted male rats was suppressed to a greater extent. 6. All alterations in muscle function during chronic K+ depletion were restored to normal after 2 weeks K+ repletion. 7. The results suggest that there is a preponderance for male over female rats in developing alterations in skeletal muscle function during chronic K+ deficiency. The changes may be associated with abnormalities of muscle membrane permeability and cellular function.

Animals↗

Enhancement of fertilization by piperine in hamsters.

The effect of piperine on the fertilization of eggs with sperm was investigated in female hamsters. They were intragastrically treated with piperine at doses of 50 and 100 mg/kg BW from day 1 through day 4 of the oestrous cycle. During piperine treatment, these females were superovulated and artificially inseminated (AI) with spermatozoa from untreated male hamsters at 12 h after hCG injection. The fertilization and growth of embryos were examined at various times after AI. In control hamsters, the percent fertilization increased with time, from 27.4 +/- 3.3% at 9 h after AI to 75.3 +/- 9.6 at 24 h after AI. Administration of piperine to the superovulated animals markedly enhanced the percent fertilization at 9 h after AI. It was increased to 85.4 +/- 4.1 and 82.8 +/- 4.8% by piperine at doses of 50 and 100 mg/kg BW, respectively. However, examination of the embryos retrieved 48 h after AI revealed no differences in the stage of embryonic development among different groups of animals. The possibility that this effect was due to the direct action of vanillic acid, a major piperine metabolite, was tested in vitro. Direct exposure of spermatozoa to vanillic acid at doses 25-100 mg% did not significantly affect their motility, percent acrosome reaction or fertilizing ability. This suggests that the enhancement of fertilization by piperine treatment was not related to the secretion of vanillic acid into the oviduct.

Alkaloids↗

Hypolipidemic effect of Curcuma comosa in mice.

The hypolipidemic effect of an ethyl acetate extract of the rhizome of Curcuma comosa Roxb was investigated in mice. Intragastric administration of the extract significantly decreased plasma lipid levels of both triglyceride and cholesterol but increased liver triglyceride content. Liver weight and plasma activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were not affected by a single administration. Prolonged treatment did not further decrease plasma lipid level but caused further increases in liver triglyceride content and weight. The lower plasma cholesterol activity of C. comose extract was found to be essentially associated with elevation of plasma HDL cholesterol level, increased excretion of fecal cholesterol and bile salt. The increase persisted throughout the period of treatment. These results suggest that C. comosa has hypolipidemic action. It exerts hypocholesterolemic activity by accelerating mobilization of cholesterol from peripheral tissues into liver and enhancing excretion of cholesterol and bile salt into feces.

Animals↗

Inhibitory effect of steviol, a metabolite of stevioside, on glucose absorption in everted hamster intestine in vitro.

The effects of stevioside and steviol (a product of enzymatic hydrolysis of stevioside) on intestinal glucose absorption were examined in hamster jejunum. By using the everted sac technique, we found that stevioside (1 and 5 mM) had no inhibitory effect on glucose absorption. In contrast, glucose absorption was inhibited 29% by 1 mM steviol. The inhibition of glucose absorption by steviol was related to steviol concentration and incubation time. The possible mechanism of steviol inhibitory action of glucose absorption was also investigated. Reductions in the intestinal mucosal ATP content and absorptive surface area were responsible for the inhibition of glucose absorption by steviol. The decrease in the intestinal mucosal ATP content was accompanied by a decrease in the activities of mitochondrial NADH cytochrome c reductase and cytochrome oxidase. Moreover, no inhibitory effects of steviol on the activity of intestinal Na+,K(+)-ATPase and glucose uptake in the intestinal brush-border membrane vesicles were seen. These results suggest that inhibition of intestinal glucose absorption by steviol in hamsters is due to the reduction in mucosal ATP content and an alteration of the morphology of the intestinal absorptive cells.

Adenosine Triphosphate↗

Potentiation of carbon tetrachloride hepatotoxicity by piperine.

The effect of piperine on CCl4-induced hepatotoxicity was investigated in rats. Piperine pretreatment potentiated the hepatotoxicity of CCl4 in a dose-dependent manner. The maximum potentiation occurred when piperine at a dose of 100 mg/kg BW was intragastrically administered 4 h prior to an intraperitoneal injection of CCl4, at which time the activities of plasma glutamic pyruvic transaminase (PGPT) and plasma glutamic oxaloacetic transaminase (PGOT) were elevated by 70-80%. Concurrent with the rise in PGPT and PGOT activities, the accumulation of hepatic triglyceride increased whereas the plasma level of triglyceride decreased. Piperine pretreatment also potentiated CCl4-induced lipid peroxidation in the liver. The extent of potentiation correlated well with the rise of hepatic enzyme activity in plasma. In the in vitro system in which the tissue was preincubated with piperine and CCl4 was added into the incubation medium, piperine also exhibited a concentration dependent potentiation on CCl4-induced lipid peroxidation and on the activity of NADPH-cytochrome c-reductase. The results indicated that piperine potentiated CCl4-induced hepatotoxicity by interacting with liver cells and increased the activity of NADPH-cytochrome c reductase. The increase in activity of this enzyme accelerated biotransformation of CCl4, thereby increasing lipid peroxidation and enhancing hepatotoxicity.

Alanine Transaminase↗

Gastric mucosal secretions and lesions by different doses of streptozotocin in rats.

The effects of various doses of streptozotocin (STZ) on gastric mucosal secretions and lesions were investigated in rats. STZ at a dose as low as 30 mg/kg significantly increased plasma glucose (P less than 0.05). The elevation of plasma glucose was dependent on the dose on STZ (30-65 mg/kg) administered. The levels of SGOT, SGPT, bilirubin and BUN also increased with the dose of STZ. The secretory rate of gastric H+ decreased whereas the degree of mucosal hyperemia increased with increasing levels of plasma glucose. Treatment with insulin improved all abnormal conditions except the gastric mucosal lesions. The lesions occurred with low H(+)-secretory rate and low gastric emptying rate. It is suggested that STZ might act directly on the gastric mucosa. Its action depended on the dose administered and was not primarily related to the insulin deficit.

Alanine Transaminase↗

Effects of piperine on hamster sperm capacitation and fertilization in vitro.

The effect of piperine on the fertilizing ability of hamster sperm was investigated in vitro. Sperm were incubated in a capacitation medium for 3 h prior to co-incubation with hamster eggs in a fertilization medium for another 3 h. Addition of 0.18-1.05 mM piperine to the capacitation medium reduced both the percentage of eggs fertilized and the degree of polyspermia in a dose-dependent manner. When piperine was added to the fertilization medium alone, a significant reduction in fertilization was observed only at high doses (0.70-1.05 mM). The presence of piperine in the capacitation medium inhibited the acrosome reaction in a dose-dependent manner but had no effect on sperm motility, whether this was measured quantitatively or qualitatively. Piperine also inhibited the influx of calcium into sperm during capacitation. It is suggested that such an inhibition might be a major cause of a reduction of the acrosome reaction and the subsequent impairment of fertilizing ability of sperm.

Acrosome↗

Gastric mucosal lesions in streptozotocin-diabetic rats.

Formation of gastric mucosal lesions by streptozotocin-induced diabetes was investigated in rats. A single intravenous administration of streptozotocin in a dose of 65 mg/kg effectively produced hyperglycemia and damaged the gastric mucosa. Incidence and severity of mucosal lesions were progressively increased with time, from one to six weeks posttreatment. Microscopic lesions of the mucosa included hyperemia, desquamation of the surface epithelium with diffuse hemorrhage, and severe hemorrhage with localized erosion. Concurrent to the hyperglycemia, the histamine stimulated gastric H+-secretion was significantly decreased whereas pepsin secretion was not affected. Both soluble mucus and surface mucus gel were increased. The result suggests that the early lesion of gastric mucosa may be associated with the direct action of streptozotocin, the severity of which may be further aggravated by diabetic state.

Animals↗

Effects of cortisol pretreatment on the acute hepatotoxicity of aflatoxin B1.

Effects of cortisol pretreatment on acute hepatotoxicity induced by aflatoxin B1 (AFB1) were investigated in female rats. Pretreatment of cortisol (1.0-10.0 mg/kg body weight) for 7 consecutive days markedly increased mortality rate, activity of plasma glutamic pyruvic transaminase (PGPT), plasma glutamic oxaloacetic transaminase (PGOT) and liver triglycerides induced by AFB1 (3.0 mg/kg body weight). The potentiating action of cortisol on hepatic necrosis of AFB1 showed a dose-dependent pattern. The possible mechanism of its action may be related to an increase in the activity of aniline hydroxylase and formation of AFB1-2,3-epoxide which in turn caused a marked increase in AFB1 binding to hepatic DNA and proteins, and lipid peroxide formation. Therefore, the potentiating action of cortisol on AFB1 hepatotoxicity may possibly increase the damage to DNA and membranes of various organelles.

Aflatoxin B1↗

Effects of cytochalasin E on H+ and volume secretion in gastric fistula rats.

Effects of cytochalasin E on the secretion of H+ and volume of gastric juice were investigated in gastric fistula rats. Direct exposure of the gastric mucosa to cytochalasin E (5-20 micrograms/ml) inhibited H+ secretory rate in all of the pentagastrin-, histamine- as well as non-stimulated rats but it did not affect the secretory volume of gastric juice. The inhibitory action of cytochalasin E on H+ secretion had a rapid onset and showed a dose-dependent pattern. The mechanism of inhibitory action was not related to its interaction with plasma membrane receptors or membrane enzyme, K+-stimulated ATPase. Interference with cellular energy production as well as alteration of microfilament function, which are essential for H+ production and secretion respectively, are likely to be the bases of the cytochalasin inhibition.

Animals↗

Stimulation of gastric mucus and protein secretion by cytochalasin E in rats.

Effects of cytochalasin E on the secretion of mucus and protein were investigated in gastric fistula rats. Direct exposure of the gastric mucosa to cytochalasin E (5-20 micrograms/ml) significantly stimulated the secretory rate of soluble mucus and protein in pentagastrin-stimulated rats. The amount of surface mucus gel was also increased. The stimulatory effect was increased with increased concentrations of cytochalasin. Histological study suggests that the cytochalasin stimulated the release of mucus from the cell. The increase in secretory rate of protein was not due to an increase of pepsin secretion but rather was the consequence of the increase in mucus secretion.

Animals↗

Acute toxicity of nimbolide and nimbic acid in mice, rats and hamsters.

Nimbolide and nimbic acid are toxic to mice only when given i.p. and i.v. but they are less toxic to rats and hamsters. The LD50 values of a single i.p. administration of nimbolide to adult male, female and weanling mice were 225, 280 and 240 mg/kg body wt, respectively, and its i.v. LD50 value was decreased to 24 mg/kg body wt in adult male mice. No fatality was observed when nimbolide was given i.g., i.m. and s.c. to adult male mice. Estimated LD50 values of nimbolide in rats and hamsters were somewhat higher than 600 and 500 mg/kg body wt. After 12-23 h i.p. administration of a lethal dose, most animals died of possible dysfunctions in kidney (tubular necrosis), small intestine (hemorrhagic necrosis), pancreas (acinar cell necrosis) and liver (mild fatty infiltration and focal necrosis). In contrast, mice and rats given a lethal dose of nimbolide (i.v.) died of a marked and sudden drop in arterial blood pressure and respiratory paralysis within about 1-18 min. Nimbic acid was less toxic to mice with an i.v. LD50 value of 265 mg/kg body wt and i.p. and i.g. LD50 values of higher than 600 mg/kg body wt. The possible cause of death induced by nimbic acid may be similar to that of nimbolide given i.v. and this is a sudden hypotensive shock.

Administration, Oral↗

Antifertility effect of Citrus hystrix DC.

An alcohol and chloroform extract of Citrus hystrix DC. fruit peel was investigated for antifertility activity in pregnant rats by oral administration at different periods of gestation. The extracts were found to effectively inhibit implantation, produce abortion and slightly hasten labor time when it was given from day 2 to 5, day 8 to 12 and day 15 until labor, respectively. At the same dose level which interrupted pregnancy, the extract did not affect the estrous cycle. Neither uterotrophic effects nor induction of vaginal cornification was observed when it was given to spayed rats. However, the extract enhanced the uterotrophic effect of estradiol when both were simultaneously given. Additionally, the extract stimulated uterine contractions observed in an in situ study. It is suggested that these two effects may be responsible for the interruption of pregnancy associated with the extract.

Abortifacient Agents, Nonsteroidal↗

Depression of estrogen-induced uterine peroxidase in alloxan-diabetic rats.

The influence of alloxan diabetes on reproductive function and the estradiol-stimulated increase in uterine peroxidase was investigated. Alloxan monohydrate in a dose of 75 mg/kg body weight effectively produced permanent diabetes. In adult rats, 20 days of diabetes resulted in cessation of the estrous cycle and a significant reduction in the gain of body weight, the weights of anterior pituitary gland, ovary, uterus, the level of serum progesterone and the activity of the estradiol-stimulated uterine peroxidase (P less than 0.05). After 10 days of insulin treatment, the ovarian weight, the estrous cycle and the level of ovarian hormones were restored to normal whereas the uterine weight and the estradiol-stimulated uterine peroxidase activity were only partially recovered. Persistent depression of the uterine response in the insulin-treated diabetic rats to both endogenous and exogenous ovarian hormone stimulation suggests that the uterus was directly affected by diabetes. The direct effect of diabetes upon the uterus was further demonstrated in the ovariectomized immature rat in which diabetes depressed the stimulatory action of estradiol on both uterine weight and uterine peroxidase activity.

Animals↗

Acute and subacute toxicity of piperine in mice, rats and hamsters.

Piperine is acutely toxic to mice, rats and hamsters. The LD50 values for a single i.v., i.p., s.c., i.g. and i.m. administration of piperine to adult male mice were 15.1, 43, 200, 330 and 400 mg/kg body wt, respectively. The i.p. LD50 value was increased to 60 mg/kg body wt in adult female and 132 mg/kg body wt in weanling male mice. In adult female rats, the i.p. LD50 value was 33.5 mg/kg body wt whereas the i.g. LD50 value was increased to 514 mg/kg body wt. Most animals given a lethal dose died of respiratory paralysis within 3-17 min. In subacute toxicity studies, the rats died within 1-3 days after treatment. Histopathologic changes included severe hemorrhagic necrosis and edema in gastrointestinal tract, urinary bladder and adrenal glands. Death of these animals may be attributable to multiple dysfunctions in their organs.

Adrenal Gland Diseases↗

Effect of estradiol treatment on the secretion and structure of gastric H+ and pepsin-secreting cells in the rat.

Gastrin-stimulated secretory rate of gastric H+ and pepsin were markedly inhibited (P less than 0.001) in ovariectomized rat after 7 days of estradiol treatment (80 micrograms/kg/day) in comparison to ovariectomized untreated rat and sham control. In correlation to the secretions, the majority of parietal cells failed to show the typical ultrastructural transformation associated with active secretion. Pyknotic nuclei with dilatation of nuclear envelope and degenerative changes were observed in the parietal cells. Meanwhile, the chief cell showed inactive characteristics in that a large number of pepsinogen granules were retained in the cells. In contrast, in ovariectomized untreated rat, the rate of gastrin-stimulated H+ and pepsin secretion were not significantly different from the sham (P greater than 0.05). Consistent with secretion, after gastrin stimulation, the morphology and ultrastructure of the parietal cell and chief cell showed active secretory features in a pattern similar to changes observed in sham. The results suggest that impairment in the structure of the functional parts of secretory cells by estrogen treatment was a factor contributing to the inhibition of the gastric secretions.

Animals↗