Reduced normogastric electrical activity associated with emesis:A telemetric study in ferrets

AIM： To characterize the gastric myoelectric activity （GMA） and intra-abdominal pressure changes induced by emetic stimuli （apomorphine and cisplatin） in the ferret. METHODS： GMA and intra-abdominal pressure were recorded in conscious, unrestrained ferrets surgically implanted with radiotelemetry transmitters. Animals were challenged with apomorphine （0.25 mg/kg sc） and cisplatin （10 mg/kg ip）, and the emetic response was quantified via direct observation and intra-abdominal pressure recording for 1 and 4 h, respectively. The GMA was analyzed by spectral analysis; the parameters used to characterize the GMA were the dominant frequency （DF） and the repartition of spectral power in the bradygastric, normogastric and tachygastric frequency ranges. RESULTS： Retches were identified on the intraabdominal pressure trace as peaks 0.30 ± 1.01 s in duration and 59.57 ± 2.74 mmHg in amplitude, vomit peaks were longer （0.82 ± 0.06 s, P 〈 0.01） and reached a higher pressure （87.73 ± 8.12 mmHg, P 〈 0.001）. The number of retches and vomits quantified via direct observation [apomorphine： 65.5 ± 11.8 retches ± vomits （R＋V）, cisplatin： 202.6 ± 64.1 R＋V] and intra-abdominal pressure （apomorphine： 68.3± 13.7 R＋V, n = 8; cisplatin： 219.0 ± 69.2 R＋V, n = 8） were correlated （r = 0.97, P 〈 0.0001） and the timing of emesis was consistent between the 2 methods. Apomorphine induced a decrease in normogastria from 45.48% ± 4.35% to 36.70 ± 4.34% （n = 8, P 〈 0.05） but the DF of the slow waves was not changed [8.95 ± 0.25 counts/rain （cpm） vs 8.68 ± 0.35 cpm, n = 8, P 〉 0.05]. Cisplatin induced a decrease in normogastria from 55.83% ± 4.30% to 29.22% ± 5.16% and an increase in bradygastria from 14.28% ± 2.32% to 31.19% ± 8.33% （n = 8, P 〈 0.001） but the DF （9.14 ± 0.13 cpm） remained unchanged （P 〉 0.05）. The GMA changes induced by cisplatin preceded the emetic response as normogastria was reduced for 1 h before the onset of emesis （57.61% ± 5.66% to 39.91% ± 5.74%, n = 6, P 〈 0.05）. Peri-emesis analysis revealed that the GMA was significantly disturbed during and immediately after, but not immediately before, the emetic episodes. CONCLUSION： The induction of emesis is reliably associated with a disrupted GMA, but changes may also occur prior to and following the emetic response.

Anti-emetic mechanisms of Xiaobanxia Tang decoction on the chemotherapy-induced pica model in rats

OBJECTIVE To investigate the mechanisms of Xiaobanxia Tang(XBXT)in the prevention and treatment of chemotherapy-induced nausea and vomiting.METHODS The chemotherapy-induced rat pica model was established by intraperitoneal injection of cisplatin 6mg·kg-1.Kaolin consumption was used as an indicator of nausea and vomiting.Wistar male rats were randomly divided into normal control,XBXT normal control,model,ondansetron treating,XBXT decoction high and low dose groups.The rats in ondansetron group,XBXT normal control group,XBXT high and low dose groups were gavaged ondansetron 2.6mg·kg-1·d-1,XBXT 1.6,3.2and 1.6g·kg-1·d-1,respectively 1hbefore cisplatin injection,and the administration were given every 12 h.Kaolin consumptions were weighed every 12 h.After 24 hand 72hof cisplatin injection,animals were sacrificed respectively.The contents of 5-HT,5-HIAA,dopamine(DA),DOPAC,substance P(SP),TPH,MAO and TH were measured by ELISA.The mRNA expression of 5-HT transporter(SERT),5-HT3 Areceptor,SP precursor(PPTA),NK1 and D2receptors in rat ileum and medulla oblongata were measured by RT-PCR,the protein expression were measured by Western blotting.RESULTS The high and low dosages of XBXT could significantly inhibit kaolin consumptions in cisplatin-treated rats,and reduce5-HT,increase 5-HIAA contents and reduce 5-HT3 Areceptor mRNA and protein expression,above effects are related to the reduction of TPH and the enhancement of MAOA levels.The two dosages of XBXT could significantly reduce SP and NK1 mRNA and protein expression,which was related to the reduction of PPTA mRNA expression.XBXT could also significantly reduce DA contents and D2 receptor mRNA and protein expression,which was related to the reduction of TH.CONCLUSION XBXT has significant antiemetic effect in chemotherapy-induced nausea and vomiting,the underlying mechanisms are related to the inhibition of 5-HT and5-HT3 Areceptor,SP and NK1 receptor,DA and D2 receptor.

Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs

AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration.

Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

Objective:To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods:The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath.The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System.The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis,respectively.Results:The total phenolic and total flavonoids contents of the extract were(267.75±5.77)mg GAE/g and(73.86±6.01)mg QE/g,respectively.Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC_(50)value of 0.016 mg/m L,which was blocked by atropine(0.3μM).Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC_(50)value of 2.185 mg/mL.Furthermore,Argemone mexicana extract relaxed potassium(80 mM)-induced contractions(EC_(50):9.07 mg/mL),similar to a standard drug verapamil.The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract(1-5 mg/mL)and verapamil(0.1-1μM).In addition,the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks.Conclusions:Argemone mexicana shows cholinergic agonist and calcium channel blocker activities,as well as antiemetic effect.It may be used as a potential agent for treating gastrointestinal disorders.