Inhibition Of Spontaneous Motility Research Articles

Bisphenol AP Exposure-Induced Inflammatory Response in Zebrafish Embryos Revealed by Transcriptomic Analysis.

Bisphenol AP (BPAP) is a bisphenol analogue that is used as a substitute for BPA in industrial production and is now commonly found in the environment. Currently, there is limited information available on its developmental toxicity in aquatic organisms. This study exploited zebrafish embryos to investigate the adverse effects of BPAP exposure during their early life stages. The results revealed that BPAP had a median lethal concentration (LC50) of 36, 22, and 8.5 μmol/L for zebrafish embryos at 24, 48, and 72 h post fertilization (hpf), respectively. Additionally, exposure to BPAP led to abnormal development in zebrafish embryos, including hatching delay, malformation, and inhibition of spontaneous movements. Transcriptomic analysis further revealed that BPAP exposure upregulated the mRNA expression levels of genes related to inflammatory pathways, such as il1b, ptgs2b, and fosab, indicating the induction of an inflammatory response. Overall, our findings provide early and valuable insights into the environmental and health risks associated with BPAP exposure.

“Half-Sandwich” Ruthenium Complexes with Alizarin as Anticancer Agents: In Vitro and In Vivo Studies

Upon exploration of the chemistry of the combination of ruthenium/arene with anthraquinone alizarin (L), three new complexes with the general formulas [Ru(L)Cl(η6-p-cymene)] (C1), [Ru(L)(η6-p-cymene)(PPh3)]PF6 (C2), and [Ru(L)(η6-p-cymene)(PEt3)]PF6 (C3) were synthesized and characterized using spectroscopic techniques (mass, IR, and 1D and 2D NMR), molar conductivity, elemental analysis, and X-ray diffraction. Complex C1 exhibited fluorescence, such as free alizarin, while in C2 and C3, the emission was probably quenched by monophosphines and the crystallographic data showed that hydrophobic interactions are predominant in intermolecular contacts. The cytotoxicity of the complexes was evaluated in the MDA-MB-231 (triple-negative breast cancer), MCF-7 (breast cancer), and A549 (lung) tumor cell lines and MCF-10A (breast) and MRC-5 (lung) nontumor cell lines. Complexes C1 and C2 were more selective to the breast tumor cell lines, and C2 was the most cytotoxic (IC50 = 6.5 μM for MDA-MB-231). In addition, compound C1 performs a covalent interaction with DNA, while C2 and C3 present only weak interactions; however, internalization studies by flow cytometry and confocal microscopy showed that complex C1 does not accumulate in viable MDA-MB-231 cells and is detected in the cytoplasm only after cell permeabilization. Investigations of the mechanism of action of the complexes indicate that C2 promotes cell cycle arrest in the Sub-G1 phase in MDA-MB-231, inhibits its colony formation, and has a possible antimetastatic action, impeding cell migration in the wound-healing experiment (13% of wound healing in 24 h). The in vivo toxicological experiments with zebrafish indicate that C1 and C3 exhibit the most zebrafish embryo developmental toxicity (inhibition of spontaneous movements and heartbeats), while C2, the most promising anticancer drug in the in vitro preclinical tests, revealed the lowest toxicity in in vivo preclinical screening.

In vitro anthelmintic activity of Physalis minima ethanolic leaves and stem extracts against Paramphistomum cervi from cattle

BackgroundCrude ethanolic extracts of leaves and stem of Physalis minima (Solanaceae) were evaluated for in vitro anthelmintic activity on the Bangladeshi mature parasitic flatworm Paramphistomum cervi (Trematoda) in cattle. To compare the test results, Albendazole was used as a standard drug.MethodsA leaves and stem extract of the P. minima was prepared in a Soxhlet apparatus using ethanol as a solvent. After concentrating in a vacuum rotary evaporator, the extract was analyzed for phytochemical activities. In vitro anthelmintic activity was tested against the flat worm P. cervi.ResultsThe results of anthelmintic activity of P. minima were evaluated by paralysis instead of taking as of the paralysis time and death time of the flatworm. The study concluded that the ethanolic leaves and stem extracts of P. minima had anthelmintic activity in a dose-dependent inhibition of spontaneous motility of flatworm. From the screening experiment, the crude extracts showed the best anthelmintic activity. Furthermore, our phytochemical studies point out that ethanolic extract of the leaves and stem of P. minima contains flavonoids, phenols alkaloids, terpenoids, tannins, steroids, proteins and cardiac glycosides.ConclusionsThe studies of total phenolic and flavonoids content were quantified for all parts of the plant. The results of the present study suggest that P. minima extracts are a promising alternative to the commercially available anthelmintics for the treatment of gastrointestinal nematodes of cattle. Further research is required to confirm the possibility of the antimicrobial and antiproliferative applications.

Environmental level of bisphenol F induced reproductive toxicity toward zebrafish

Bisphenol F (BPF), as an important bisphenol A substitute, is being increasingly used for industrial production. Here we performed large scale fecundity test for zebrafish that are continuous exposed to environmental levels of BPF (0.5, 5 and 50 μg/L) from embryonic stage, and identified suppressed spawning capacity of females and reduced fertility rate of males in adulthood. Although pathological change is only observed in female gonads, the transcriptional change in the hypothalamic-pituitary-gonad axis genes occurred in the gonads of both female and male fish at 150 days post-exposure. F1 generation embryos showed abnormal developmental outcomes including decreased heart rate, reduced body length, and inhibition of spontaneous movement after parental exposure to BPF. RNA-sequencing showed that the genes involved in skeletal/cardiac muscle development were significantly altered in F1 embryos spawned by BPF-treated zebrafish. The advanced pathway analysis showed that cancer and tumour formation were the most enriched pathways in the offspring of 0.5 and 5.0 μg/L groups; organismal development and cardiovascular system development were mainly affected after parental exposure to 50 μg/L of BPF; these changes were mediated by several involved regulators such as GATA4, MYF6, and MEF2C. These findings confirmed that long-term exposure to BPF at environment relevant concentration would result in reproductive toxicity among zebrafish indicating the urgent demand for the control of BPA substitutes.

TOXICOLOGICAL STUDIES ON BESTATIN

Studies on acute toxicities of bestatin (NK421) were carried out in both sexes of mice and rats, and male dogs. NK421 was administered subcutaneously, intraperitoneally and orally in mice and rats, and orally in dogs respectively. Mice and rats were observed for 14 days after treatment and LD50 values were calculated by the probit method. NK421 showed very low toxicity and no death occurred in any species following the oral administration of the maximum dose capable of dosing such as 4 g/kg for mice, 2 g/kg for rats and 1.2 g/kg for dog. General toxic signs seen in mice and rats following subcutaneous and intraperitonial injections were as follows; depression, suppressed movement, piloerection, inhibition of spontaneous movement, anorexia and emaciation. Death occurred within 5 days after administration. The toxic target organs of NK421 were found to be kidney, lymphoid tissue and liver based on histopathological examination of dead animals.

ANTHELMINTIC ACTIVITY OF OUGEINIA OOJEINENSIS (ROXB) HOCHR ROOT

The aqueous and alcoholic extracts were evaluated for both In-vitro anthelmintic activity using earth worms, round worms and tape worms. Two different doses of 50mg/ml and 100mg/ml concentration of two different extracts on comparison with albendazole. In-vivo anthelmintic activity was done on sheep. The extract of Ougeinia oojeinensis exhibited a dose dependent inhibition of spontaneous motility (paralysis) and evoked responses to pin prick. Both the extract shows the significant anthelminitic activity.

In vitro evaluation of anthelmintic activity of Nauclea orientalis leaves

Antianthelmintic activity of successive extracts (chloroform, acetone, ethanol and aqueous) of Nauclea orientalis leaves were evaluated separately on adult Indian earthworm (Pheretima posthuma) and compared with that of albendazole. It was found that the extracts exhibited, respectively dose-dependent action and inhibition of spontaneous motility (paralysis) and death of earthworms. The results indicated that the chloroform, ethyl acetate and ethanol extracts were more potent.

Effects of excitatory and inhibitory neurotransmission on motor patterns of human sigmoid colon in vitro

To characterize the in vitro motor patterns and the neurotransmitters released by enteric motor neurons (EMNs) in the human sigmoid colon. Sigmoid circular strips were studied in organ baths. EMNs were stimulated by electrical field stimulation (EFS) and through nicotinic ACh receptors. Strips developed weak spontaneous rhythmic contractions (3.67+/-0.49 g, 2.54+/-0.15 min) unaffected by the neurotoxin tetrodotoxin (TTX; 1 microM). EFS induced strong contractions during (on, 56%) or after electrical stimulus (off, 44%), both abolished by TTX. Nicotine (1-100 microM) inhibited spontaneous contractions. Latency of off-contractions and nicotine responses were reduced by N(G)-nitro-L-arginine (1 mM) and blocked after further addition of apamin (1 microM) or the P2Y(1) receptor antagonist MRS 2179 (10 microM) and were unaffected by the P2X antagonist NF279 (10 microM) or alpha-chymotrypsin (10 U mL(-1)). Amplitude of on- and off-contractions was reduced by atropine (1 microM) and the selective NK(2) receptor antagonist Bz-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH(2) (1 microM). MRS 2179 reduced the amplitude of EFS on- and off-contractions without altering direct muscular contractions induced by ACh (1 nM-1 mM) or substance P (1 nM-10 microM). Latency of EFS-induced off-contractions and inhibition of spontaneous motility by nicotine are caused by stimulation of inhibitory EMNs coreleasing NO and a purine acting at muscular P2Y(1) receptors through apamin-sensitive K(+) channels. EFS-induced on- and off-contractions are caused by stimulation of excitatory EMNs coreleasing ACh and tachykinins acting on muscular muscarinic and NK(2) receptors. Prejunctional P2Y(1) receptors might modulate the activity of excitatory EMNs. P2Y(1) and NK(2) receptors might be therapeutic targets for colonic motor disorders.

Anthelmintic activity of the crude extracts of Ficus racemosa

Th e crude extracts of Ficus racemosa (Moraceae) were evaluated for anthelmintic activity using adult earthworms; the bark extract of Ficus racemosa exhibited a dose-dependent inhibition of spontaneous motility (paralysis) and evoked responses to pin-prick. With higher doses (50 mg/mL of aqueous extract), the eff ects were comparable with that of 3% piperazine citrate. However, there was no fi nal recovery in the case of worms treated with aqueous extract in contrast to piperazine citrate with which the paralysis was reversible and the worms recovered completely within 5 h. Th e result shows that the aqueous extract possesses wormicidal activity and thus, may be useful as an anthelmintic. Key words: Anthelmintic, earthworm, Ficus racemosa, paralysis, piperazine citrate, wormicidal

In vitro antifilarial potential of the leaves and stem extract of Pluchea lanceolata on the cattle filarial parasite Setaria cervi

The effect of alcohol and aqueous extracts of the leaves and stem of Pluchea lanceolata on the spontaneous movements of both the whole worm and the nerve muscle preparation of Setaria cervi, and on the survival of microfilariae in vitro was studied. Alcohol and aqueous extracts of the leaves and stem of P. lanceolata caused the inhibition of spontaneous movements of the whole worm and the nerve muscle preparation of S. cervi, characterized by short lasting small increase in tone and amplitude of contractions followed by paralysis. The concentrations required to inhibit the movements of whole worm and nerve muscle preparations for alcohol extract were 200 and , and for aqueous extract were 250 and , respectively, suggesting a cuticular permeability barrier. Both the extracts (alcohol and aqueous) caused death of microfilariae in vitro, and being 12 and 18 ng/ml for alcohol extract and 25 and 40 ng/ml for aqueous extract, respectively.

Antifilarial activity of Azadirachta indica on cattle filarial parasite Setaria cervi

Alcohol and aqueous extracts of flowers of Azadirachta indica were tested in vitro for their potential antifilarial activity against whole worm, nerve muscle (n.m.) preparation and microfilariae of Setaria cervi. The effects of alcohol and aqueous extracts were similar in nature on the spontaneous movements of whole worm and nerve muscle preparation. On the whole worm, the response was characterized by initial increase in tone, rate and amplitude of contractions followed by reversible paralysis. The initial stimulant effect is likely to be due to irritant effect on the cuticle. Nerve muscle preparation responded to both extracts by inhibition of spontaneous movements followed by reversible paralysis; initial stimulation phase was absent. The inhibition was concentration related. Alcohol and aqueous extracts had almost similar lethal effect on the microfilariae of S. cervi, the LC 50 being 15 and 18 ng/ml, respectively.

Exploration of antifilarial potential and possible mechanism of action of the root extracts of Saxifraga stracheyion on cattle filarial parasite Setaria cervi.

The effect of aqueous and alcohol extracts of the roots of Saxifraga stracheyi Engl. On the spontaneous movements of both the whole worm and the nerve muscle preparation of Setaria cervi and on the survival of microfilariae in vitro was studied. Both extracts caused the inhibition of spontaneous movements of the whole worm and the nerve-muscle preparation of S. cervi, characterized by an increase in the amplitude and a decrease in the rate of contractions, while the tone of the contractions remained visibly unaffected. The concentration required to inhibit the movements of the whole worm preparation was 140 microg/ml for the aqueous and 250 microg/ml for the alcohol extract. The concentration of S. stracheyi extracts required to produce an equivalent effect on the nerve-muscle preparation was 30 microg/ml for aqueous, and 20 microg/ml for the alcohol extract, suggesting a cuticular permeability barrier.

Functional identification of rat atypical beta-adrenoceptors by the first beta 3-selective antagonists, aryloxypropanolaminotetralins.

1. We have assessed the relative abilities of compounds belonging to the new aryloxypropanolaminotetralin (APAT) class and of the reference beta-adrenoceptor-blocking agent, alprenolol, to antagonize functional responses in vitro and in vivo involving atypical (beta 3) or conventional (beta 1 and beta 2) beta-adrenoceptors. 2. The range of pA2 values for three representative APATs against inhibition of spontaneous motility in the rat isolated colon by the selective beta 3-adrenoceptor agonist, SR 58611A (8.1-8.8), was well above similarly calculated values for non-competitive antagonism of guinea-pig trachea relaxation by salbutamol (beta 2, 6.5-6.9) and the atrial chronotropic response by isoprenaline (beta 1, 6.7-7.3). Alprenolol, however, was substantially more potent in antagonizing atrial (pA2, 8.2) and tracheal (pA2, 8.9) responses than SR 58611A mediated inhibition of colonic motility (pA2, 6.8). 3. Several APAT isomers with different configurations at the chiral carbons, when tested on isolated organs, presented stringent stereochemical requirements for beta 3-selectivity, including high antagonist potency-ratios between active and inactive enantiomers. 4. In vivo, the inhibition of colonic motility and the thermogenic response of brown adipose tissue elicited in rats by the selective beta 3-adrenoceptor agonists SR 58611A and BRL 37344 respectively were substantially diminished by the representative APAT, SR 59230A, at oral doses (< or = 5 mg kg-1) well below those half maximally effective (ID50) for preventing beta 1-(isoprenaline tachycardia > or = 80 mg kg-1) or beta 2-(salbutamol bronchodilatation, 44 mg kg-1) mediated responses. Alprenolol, as expected, was a less potent and nonselective antagonist of the putative beta 3-responses. 5. These findings support APATs as the first potent, orally effective selective antagonists at beta 3-adrenoceptors, and provide final unambiguous evidence that beta 3-adrenoceptors underlie inhibition of colonic motility and brown adipose tissue thermogenesis in rats.

Specific Antiserotonergic and General Spasmolytic Activities Mediated by Artemisia scoparia

AbstractThe aqueous-methanolic extract of Artemisis scoparia (0.01 mg/ml) completely blocked serotonin-induced contractions in rat uterus while it had no effect on the agonist response of serotonin in guinea-pig ileum. At higher concentrations (0.1–0.3 mg/ml) it caused concentration-dependent inhibition of spontaneous movements of rat uterus as well as acetylcholine or serotonin-induced ileal contractions. These data indicate that the plant contains specific antiserotonergic (5HT2) blocker and general spasmolytic constituents).

Sympathetic control of motility, fluid transport, and transmural potential difference in the rabbit ileum

Both intestinal motility and intestinal fluid and electrolyte transport are influenced by the sympathetic nervous system. The aim of this study is to examine the relationship between the sympathetically induced inhibition of spontaneous contractile activity and epithelial function, monitoring simultaneously motility, fluid transport, and transmural potential difference (PD) in the rabbit ileum. Experiments were performed in vitro to eliminate any possible indirect effects on intestinal function caused by alterations in intestinal blood flow. Perivascular nerve stimulation induced an inhibition of spontaneous motility, a fall in transmural PD (toward more lumen positive), and an enhanced fluid absorption. The sympathetically induced inhibition of motility was abolished by the beta-adrenoceptor antagonist, propranolol, whereas the subsequent administration of phentolamine, the alpha-adrenoceptor antagonist, was required to abolish the fall in transmural PD. Thus the sympathetic nervous system is capable of simultaneously influencing intestinal motility and fluid and electrolyte function. However, separate but parallel neural mechanisms control the smooth muscle and epithelial responses; the inhibition of motility is beta-mediated, while alpha-receptors alter fluid and electrolyte transport.

Development of the extrinsic sympathetic innervation to the enteric neurones of the rat small intestine

The development of the sympathetic control of motility of the small intestine of the rat has been studied over the early postnatal period. An inhibition of spontaneous motility was recorded in response to stimulation of the mesenteric paravascular nerve bundles as early as 3–4 days postnatal. At this time, the ganglia of the myenteric plexus were well supplied with noradrenergic nerve fibres, while not all of the ganglia of the submucous plexus were contacted by fibres until 6 days postnatal. The sympathetic innervation to the submucous arteries developed even later and at 9 days postnatal was still less dense than in adults. The onset of sympathetic function in the gut preceded that in the mesenteric arteries by several days. These results further support the hypothesis that the sympathetic neurones supplying the enteric ganglia are a subpopulation of cells distinct from those supplying the blood vessels of the mesentery and submucosa.

Pharmacological properties of musk

1. 1. The general pharmacological properties of musk were studied. 2. 2. After the application of musk, inhibition of acetic acid-induced writhing, hemolytic effect and excitation of spontaneous uterine motility of rats, inhibition of spontaneous motility in isolated ileum of rabbits, and anti-inflammatory effects and potentiation of β-adrenergic action in isolated preparations of guinea pig trachea were observed. 3. 3. These effects were not observed after application of muscone or allantoin, constituents of musk.

Generalized electrocortical activation by cortical stimulation in the cat

1. 1. In the cat, the cerebral cortical areas have been determined from which on electrical stimulation a generalized electrocortical activation (desynchronization) can be elicited (fig. 1). 2. 2. Positive sites were located in (i) the medial frontal cortex and the cingulate and hippocampal gyri; (ii) the intermediate lateral frontal cortex; (iii) the temporo-occipital cortex; (iv) the orbito-insulo-temporal polar region; and (v) the parietal cortex. 3. 3. The responsive areas correspond to those from which a behavior “attention” response, various autonomic effects, and inhibition of spontaneous movements can be obtained. Through projections to the brain stem or thalamic reticular areas these cortical fields probably contribute to the initiation and maintenance of wakefulness and directed attention.

The motility and reactivity of the oestrogenized rabbit uterus in vivo; with comparative observations on milk ejection.

SUMMARY The spontaneous motility of the intact uterus of spayed oestrogenized rabbits under sodium pentobarbitone anaesthesia has been recorded. Both uteri of each animal behaved similarly, and contractions often appeared to be synchronous. Small changes of load affected the amplitude of contractions, but did not alter uterine responsiveness to neurohypophysial or adrenomedullary hormones. Mid-thoracic section of the spinal cord obliterated spontaneous motility of the uterus; spinal anaesthesia did not. Spontaneous motility persisted for as long as 7 hr after decerebration and removal of the pituitary gland. The threshold dose of oxytocin for activating the oestrogenized uterus was the same as that for the lactating mammary gland, i.e. 1–5 mu. Doses up to 50 mu. usually gave an increase in frequency and amplitude of contractions. In the same dose range vasopressin either had little effect or inhibited spontaneous uterine motility, although milk ejection was stimulated. Slow infusion of oxytocin at rates of 1·5–48 mu./min produced graded increases in the rate and depth of uterine contractions and, at the same time, in similarly treated, lactating animals, rhythmic milk-ejection responses which at the higher rates of infusion merged to give a tetanic (plateau) type of milk ejection. Adrenaline or noradrenaline in doses of 1–5 μg produced diphasic uterine responses, initial contractions being followed by inhibition of spontaneous motility. They also inhibited the uterine, as well as the milk-ejection response to oxytocin injected 10–30 sec later. The inhibitory effect of adrenaline on both organs was about twice that of noradrenaline. The above-mentioned responses to adrenaline and oxytocin could also be elicited by electrical stimulation of the hypothalamus. Stimuli in the dorsal, lateral, perifornical and posterior hypothalamic areas produced effects equivalent to those of 1–5 μg adrenaline on both the uterus and mammary gland. These responses were abolished by mid-thoracic section of the spinal cord or by spinal anaesthesia. In such preparations responses typical of those produced by oxytocin were seen in both organs after stimulation of the paraventricular nuclei, supraoptic nuclei and the hypothalamo-hypophysial nerve pathways of the tuber cinereum and neural stalk. Dilatation of the vagina (or rectum) gave rise to a uterine response similar to that resulting from adrenaline or noradrenaline. The response was abolished by spinal anaesthesia, but not by mid-thoracic spinal section or decerebration. The same stimuli also produced 'bearing down' contractions of the abdominal muscles. Contractions of the uterus could also be elicited by mechanical stimuli, in the absence of functional spinal connexions.