Activated Charcoal Haemoperfusion in the Treatment of Experimental Amitriptyline Poisoning in Pigs – The Effect on Amitriptyline Plasma Concentration and Haemodynamic Parameters

Coated activated charcoal haemoperfusion (CAC‐HP) is a well‐known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC‐HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC‐HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC‐HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC‐HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time‐point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC‐HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC‐HP as a treatment modality in AT‐poisoned human patients may be inadequate.     

Dose‐Dependent Adsorptive Capacity of Activated Charcoal for Gastrointestinal Decontamination of a Simulated Paracetamol Overdose in Human Volunteers

Abstract: The amount of activated charcoal needed to treat drug overdoses has arbitrarily been set at a charcoal‐drug ratio of 10:1. Recent in vitro studies have shown a larger adsorptive capacity for activated charcoal when used in a model of paracetamol overdose. In the present study, we investigated whether this reserve capacity exists in vivo. This is clinically relevant in cases of large overdoses or if the full standard dose of 50 g activated charcoal cannot be administered. We performed a randomized, cross‐over study (n = 16). One hour after a standard breakfast, 50 mg/kg paracetamol was administered, followed 1 hr later by an activated charcoal‐Water slurry containing 50 (control), 25 or 5 g activated charcoal. The areas under the serum concentration‐time curve (AUC) for paracetamol were used to estimate the efficacy of each activated charcoal dose. The AUC of the 25‐g dose was found to be of similar size compared to the control, although statistics were weak. The AUC of the 5‐g dose was 59% larger than the AUC of the 50‐g dose (p = 0.0003). The terminal elimination half‐life (t_1/2) of paracetamol was 1.6 (CI 1.4–2.0) and 1.9 (CI 1.5–2.4) hr for 50 and 25 g, respectively (NS), and 2.5 (CI 1.8–3.0) hr for the 5‐g dose (p = 0.003). The decrease in t_1/2 of paracetamol for the two larger activated charcoal doses indicates a possible effect of activated charcoal on paracetamol clearance and warrants further investigation. The large adsorptive reserve capacity of activated charcoal in vitro could not be reproduced for the smallest dose of activated charcoal. An activated charcoal‐drug ratio of 10:1 is therefore still recommendable.     

Effect of alcohol dehydrogenase‐1B and ‐7 polymorphisms on blood ethanol and acetaldehyde concentrations in healthy subjects with a history of moderate alcohol consumption

This study aims to evaluate the effect of ADH1B and ADH7 genotypes on blood acetaldehyde and ethanol levels after alcohol ingestion, and to measure the genotoxic effect of smoking and ethanol on the buccal cells, also controlling for ADH variants. We recruited healthy Italian subjects with at least a moderate history of alcohol consumption. All subjects were given an alcoholic drink of 0.4 g ethanol /kg of body weight. Blood venous samples were collected at baseline, and 30, 60, 90, and 120 minutes after ingestion. Buccal cells were collected before ethanol ingestion. Sixty subjects were enrolled in the study. Individuals with the ADH1B GG genotype had median ethanol levels of 5.0mM (IQR 3.4–7.2), and those with the ADH1B GT/TT genotype had 4.7mM (IQR 4.2–4.8). Corresponding acetaldehyde levels were 1.5μM (IQR 0.7–2.6) for ADH1B GG genotype and 1.6μM (IQR 1.5–1.7) for ADH1B CG/GG genotype. Individuals with the ADH7 CC genotype had median ethanol levels of 5.0mM (IQR 3.3–7.2), while 5.0mM (IQR 4.7–5.6) was in those with the ADH7 CG/GG genotype. Corresponding acetaldehyde levels were 1.5 μM (IQR 0.7–2.6) for ADH7 CC genotype and 1.5 μM (IQR 1.4–1.6) for ADH7 CG/GG genotypes. A non‐significant increase in the frequency of karyolitic and pyknotic cells was found in the group of heavy drinkers and current smokers, when compared to the moderate drinkers and the non‐smokers. Our study does not support the hypothesis that ADH1B and ADH7 genotypes affect blood ethanol and acetaldehyde concentration.     

Acute CO Poisoning is Associated with Impaired Fibrinolysis and Increased Thrombin Generation

Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in many countries. In ex vivo studies, CO released from carbon monoxide‐releasing molecules has been shown to attenuate fibrinolysis via increased alpha‐2‐antiplasmin activity. Hypofibrinolysis is associated with coronary ischaemia, which is also commonly observed in CO poisoning. We examined fibrin clot properties in acutely poisoned CO patients. Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 48 patients and controls matched for age and sex. CO‐poisoned patients had 11.6% longer clot lysis time than the controls (p < 0.0001). No intergroup differences in clot permeability or turbidimetric variables were observed. Plasma tissue‐type plasminogen antigen (tPA), plasminogen activator inhibitor‐1 (PAI‐1) antigen and activity and F1.2 prothrombin fragments were higher in the patients than in the controls (all p < 0.0001). Plasma tPA activity was lower in the CO‐poisoned group. Multiple linear regression showed that a thrombin generation marker, F1.2, is the strongest predictor of clot lysis time, followed by PAI‐1 activity and carboxyhaemoglobin levels. In conclusion, this report is the first to demonstrate that acute CO poisoning in human beings is linked to increased thrombin generation and impaired fibrinolysis, which might contribute to ischaemic complications.     

AlCl3 induces lymphocyte apoptosis in rats through the mitochondria–caspase dependent pathway

To investigate apoptosis mechanisms in lymphocytes induced by aluminum trichloride (AlCl₃) through the mitochondria–caspase dependent pathway, the spleen lymphocytes of rats were cultured with RPMI‐1640 medium and exposed to AlCl₃·6H₂O in the final concentrations of 0 (control group, CG), 0.3 (low‐dose group, LG), 0.6 (mid‐dose group, MG), and 1.2 (high‐dose group, HG) mmol·L^?1 for 24 h, respectively. Mitochondrial transmembrane potential (ΔΨm), cytochrome C (Cyt C) protein expression in cytoplasm, Caspase‐3 and Caspase‐9 activity, Bcl‐2, Bax, Caspase‐3 and Caspase‐9 mRNA expressions, DNA ladder and lymphocytes apoptosis index were detected. The results showed that Cyt C protein expression in cytoplasm, Caspase‐3 and Caspase‐9 activity, Bcl‐2, Bax, Caspase‐3 and Caspase‐9 mRNA expressions, the ratio of Bcl‐2 and Bax mRNA expression, lymphocytes apoptosis index increased, while ΔΨm decreased in the AlCl₃‐treated groups compared with those in CG. The results indicate that AlCl₃ induces lymphocyte apoptosis in rats through the mitochondria–caspase dependent pathway. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 385–394, 2016.     

Is complicated grief a risk factor for substance use? A comparison of substance-users and normative grievers

Background: There are no studies to date which have examined complicated grief (CG) symptomatology in substance use disorder (SUD) populations specifically. This study aimed to determine if the presence of symptoms of CG is more frequent among drug dependent patients than a control group and identify which variables could be associated with the symptomatology of CG.

Method: Sociodemographic variables, drug and bereavement related characteristics, CG symptomatology and perceived social support were examined in a sample of 196 bereaved SUD patients (78.1% men). The control group was formed by 100 bereaved non-addicted participants (73% men). A multiple linear regression analysis was conducted to identify which variables were associated with symptoms of CG.

Results: The presence of symptoms of CG among SUD patients was 34.2%, in comparison to 5% in the control group. Respondents with a higher CG symptomatology include: those being widowed (β=?0.165), those who had lost a sibling (β?=?0.253), those who had experienced a traumatic death (β?=?0.158), those without working status (β=?0.005). By contrast, being from the control group (β=??0.157), reporting secondary education (β?=??0.201) and perceived social support (β?=??0.146) were found to be protective factors.

Conclusions: These findings highlight the importance of diagnosing and treating those bereaved individuals with SUD who appear to be particularly vulnerable to develop CG symptomatology.     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Tc‐99m Glu‐Cys‐Gly‐His‐Gly‐Lys (ECG‐HGK), a novel Tc‐99m labeled hexapeptide for molecular tumor imaging

Domain 5 of kinin‐free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine–glycine–lysine (HGK)‐rich region might be responsible for inhibition of cell adhesion. The authors developed HGK‐containing hexapeptide, glutamic acid–cysteine–glycine (ECG)–HGK, and evaluated the utility of Tc‐99m ECG‐HGK for tumor imaging. Hexapeptide, ECG‐HGK was synthesized using Fmoc solid‐phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc‐99m ECG‐HGK within HT‐1080 cells was evaluated in vitro. In HT‐1080 tumor‐bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc‐99m ECG‐HGK was prepared in high yield. The uptake of Tc‐99m ECG‐HGK within the HT‐1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc‐99m ECG‐HGK was accumulated substantially in the HT‐1080 tumor (tumor‐to‐muscle ratio = 5.7 ± 1.4 at 4 h), and the tumoral uptake was blocked by the co‐injection of excess HGK (tumor‐to‐muscle ratio = 2.8 ± 0.6 at 4 h). In the present study, Tc‐99m ECG‐HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc‐99m ECG‐HGK for tumor imaging.     

Intravenous Lipid Emulsion Entraps Amitriptyline into Plasma and Can Lower its Brain Concentration – An Experimental Intoxication Study in Pigs

Intravenous lipid emulsion has been suggested as treatment for severe intoxications caused by lipophilic drugs, including tricyclic antidepressants. We investigated the effect of lipid infusion on plasma and tissue concentrations of amitriptyline and haemodynamic recovery, when lipid was given after amitriptyline distribution into well‐perfused organs. Twenty anaesthetized pigs received amitriptyline intravenously 10 mg/kg for 15 min. Thirty minutes later, in random fashion, 20% Intralipid^® (Lipid group) or Ringer's acetate (Control group) was infused 1.5 ml/kg for 1 min. followed by 0.25 ml/kg/min. for 29 min. Arterial and venous plasma amitriptyline concentrations and haemodynamics were followed till 75 min. after amitriptyline infusion. Then, frontal brain and heart apex samples were taken for amitriptyline measurements. Arterial plasma total amitriptyline concentrations were higher in the Lipid than in the Control group (p < 0.03) from 20 min. on after the start of the treatment infusions. Lipid emulsion reduced brain amitriptyline concentration by 25% (p = 0.038) and amitriptyline concentration ratios brain/arterial plasma (p = 0.016) and heart/arterial plasma (p = 0.011). There were no differences in ECG parameters and no severe cardiac arrhythmias occurred. Two pigs developed severe hypotension during the lipid infusion and were given adrenaline. In conclusion, lipid infusion, given not earlier than after an initial amitriptyline tissue distribution, was able to entrap amitriptyline back into plasma from brain and possibly from other highly perfused, lipid‐rich tissues. In spite of the entrapment, there was no difference in haemodynamics between the groups.     

A ready-to-use activated charcoal mixture

A practical, ready-to-use preparation of activated charcoal (AZU mixture) for application in toxicology has been formulated. Tb establish its efficacy, the formulation was testedin vitro and in dogs. Thein vitro adsorption capacity was compared to that of freshly prepared charcoal suspension in water (CW) and to Carbomix^®. Langmuir adsorption coefficients demonstrated small but clinically insignificant differences in adsorption capacity between the preparations. The laxative sodium sulfate did not reduce the adsorption capacity of charcoalin vitro. Dogs were given 60 mg of paracetamol per kg as an oral solution followed by 5 g of activated charcoal preparation. The area under the plasma concentration versus time curve (control 2955±353 mg·min^–1·1^–1) was significantly reduced following CW (921±453) and AZU (786±270). The premixed AZU charcoal formulation is efficacious, inexpensive and overcomes the problems of bed-side preparation. An isolated vascularly perfused rat small intestine can be used to describe the effect of activated charcoal on the intestinal secretion of theophylline.     

Multiple biological defects caused by calycosin‐7‐O‐β‐d‐glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage

Calycosin‐7‐O‐β‐d ‐glucoside (CG) is an important active isoflavone compound in Radix Astragali that has many bioactivities. However, the toxicological effects and related toxicological mechanism of CG have been rarely documented. The purpose of the present study was to evaluate the toxicity effects of CG on the model organism Caenorhabditis elegans. Some characteristics of the nematode, including lifespan, movement behavior and reproductive capacity, were used to detect the toxic effects of CG on C. elegans. The results showed that CG could shorten the lifespan of C. elegans by up to 25.3% and severely damage the movement of N2 larvae compared with the control group. Moreover, CG could prolong the generation times and reduce the brood sizes. Furthermore, CG promoted the formation of reactive oxygen species (ROS), which caused oxidative stress, increased the mRNA expression of sod‐1, sod‐2, sod‐3, sod‐5, ctl‐1, ctl‐2 and ctl‐3, and induced the antioxidant enzymes activities of superoxide dismutase and catalase to scavenge free radicals. However, antioxidant treatment experiments showed that Trolox could reduce the level of ROS caused by CG to the normal state of the control. These results suggested that the generation and elimination of ROS could not restore normal homeostasis in C. elegans treated by CG. These findings indicated that the activation of oxidative damage is one of the most important toxic mechanisms of CG in C. elegans.     

Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs

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Effect of DMPS and various adsorbents on the arsenic excretion in guinea-pigs after injection with As2O3

The present experiments were performed to test the possibility of interrupting the enterohepatic circulation of arsenic (As). Therefore the efficacy of adsorbents to bind As and/or As-DMPS adducts in vitro and their effect on the excretion of As into the feces and urine in vivo were investigated after injection of As₂O₃ and DMPS in guinea-pigs. The adsorbents bentonite, activated charcoal or colestyramine, respectively, were tested. Only slight binding of ⁷³As (<5% of the ⁷³As dose) was observed to all adsorbents in vitro. After addition of DMPS, a good binding was found for ⁷³As to colestyramine (50%) or activated charcoal (60%), respectively. However, the ⁷³As-DMPS adduct was removed from the activated charcoal during washing. In the first in vivo experiment, male guinea-pigs (n=4/group) received As₂O₃ [0.02 mmol As(III)/kg s.c. labelled with a tracer dose of ⁷³As(III) (0.14 kBq/g)], 30 min later DMPS (0.1 mmol/kg i.p.) and by gastric tube (10 ml/kg body wt) either saline, bentonite (1 g/kg), activated charcoal (1 g/kg) or colestyramine (0.2 g/kg), respectively. Urine and feces were collected for 24 h. No increase in ⁷³As excretion into the feces was observed after administration of DMPS and all adsorbents, compared to control animals. In the second in vivo experiment male guinea-pigs (n=4/group) received the same As₂O₃ (+⁷³As)-and DMPS dose. In addition, with a gastric tube (10 ml/kg) saline, colestyramine (0.2 g/kg), DMPS (0.1 mmol/kg), or the combination of DMPS (0.1 mmol/kg) + colestyramine (0.2 g/kg) were administered according to the scheme given in the following table. The amount of feces excreted did not differ between groups. Excretion of ⁷³As within the feces during the first 12 h after As injection is shown in the following table (mean±SEM). The same amount of ⁷³As (34 % of the ⁷³As dose) was excreted into the urine from animals in groups 4 and 5 during this time. Obviously, the combined oral administration of DMPS+colestyramine markedly enhanced fecal excretion of As mobilized by DMPS i.p. It is suggested that interruption of enterohepatic circulation of As may be a valuable adjunct in the treatment of As poisoning. Received: 10 January 1995/Accepted: 6 March 1995     

Administration of Activated Charcoal or Sodium Polystyrene Sulfonate (KayexalateTM) as Gastric Decontamination for Lithium Intoxication: An Animal Model

Abstract: To determine whether sodium polystyrene sulfonate (SPS; Kayexalate^TM) is effective in decreasing the absorption of lithium (Li) and to test the assumption that Li is poorly adsorbed by activated charcoal, 130 mice were administered an orogastric dose of LiCl (250 mg/kg) followed immediately by orogastric SPS (10 g/kg, SPS Group), activated charcoal (6.7 g/kg, AC Group), or water in an equivalent volume (Control Group). Subgroups of each of the 3 groups were sacrificed at 1, 2, 4 and 8 hr after treatment and serum analyzed for Li concentration. Statistical analyses revealed no overall difference between the AC Group and the Control Group. However, the SPS Group differed from both the Control and the AC Group at each time interval, with Li concentrations significantly lower in the SPS Group. These results demonstrate that: 1) SPS, in this study, effectively reduced serum Li concentrations in an in vivo model, and 2) activated charcoal did not.     

Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms

Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa‐B (NF‐кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), intracellular adhesion molecule (ICAM‐1), monocellular chemoattractant protein‐1 (MCP‐1), tumour growth factor‐ β (TGF‐β), caspase‐3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator‐activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.     

Studies with activated charcoal in the treatment of drug overdosage using the pig as an animal model

Pigs were given large oral doses of paracetamol, amylobarbitone and amitriptyline. The effect of administering activated charcoal at varying intervals after dosing on the blood drug-level profiles of paracetamol and amylobarbitone was assessed by comparison with the profiles obtained when charcoal therapy was withheld. An appreciable effect on paracetamol absorption was demonstrated when charcoal was given up to l h after dosing. The amylobarbitone-dosed pigs exhibited delayed gastro-intestinal absorption of drug and this was substantially reduced by activated charcoal given 4 hrs after dosing. The pigs metabolised amitriptyline at too high a rate for meaningful studies to be undertaken with this drug.     

Toxic effects of systemic cisplatin on rat eyes and the protective effect of hesperidin against this toxicity

Context: In the present study, cisplatin (CP) induced eye toxicity and the beneficial effect of hesperidin (HP) was investigated.

Methods: Twenty-eight rats were equally divided into four groups; the first group was kept as control. In the second and third group, CP and HP were given at the doses of 7?mg/kg and 50?mg/kg/d, respectively. In the fourth group, CP and HP were given together at the same doses. Tissue samples were collected on day 14 of CP treatment.

Results: The results demonstrated that CP caused a significant increase in thiobarbituric acid reactive substances (TBARS) levels and decrease of glutathione levels and antioxidant enzyme activity (catalase, superoxide dismutase and glutathione peroxidase) in eye tissues compared to other groups, HP prevented these effects of CP. Besides, CP led to histopathological damage in the retina and cornea. On the other hand, HP treatment prevented histopathological effects of CP.

Conclusion: CP had severe dose-limiting toxic effects and HP treatment can be beneficial against the toxic ocular effects of CP. Thus, it appears that co-administration of HP with CP may be a useful approach to attenuate the negative effects of CP on the eye.     

Sulphated Polysaccharide Isolated from the Seaweed Gracilaria caudata Exerts an Antidiarrhoeal Effect in Rodents

Diarrhoea is a significant health problem for children in developing countries that causes more than 1 million deaths annually. This study aimed to evaluate the antidiarrhoeal effect of sulphated polysaccharide (PLS) from the alga Gracilaria caudata in rodents. For the evaluation, acute diarrhoea was induced in Wistar rats (150–200 g) by administration of castor oil (10 mg/kg). Then, different parameters, including enteropooling and gastrointestinal transit and its pharmacological modulation by opioid and cholinergic pathways, were assessed using activated charcoal in Swiss Mice (25–30 g). Secretory diarrhoea was examined using cholera toxin (CT) (1 mg/loop)‐treated, isolated intestinal loops from Swiss mice (25–30 g), which were also used to examine fluid secretion, loss of chloride ions into the intestinal lumen and absorption. In addition, a GM1‐dependent ELISA was used to evaluate the interaction between PLS, CT and the GM1 receptor. Pre‐treatment with PLS (10, 30 and 90 mg/kg) reduced faecal mass, diarrhoeal faeces and enteropooling. However, 90 mg/kg more effectively reduced these symptoms; therefore, it was used as the standard dose in subsequent experiments. Gastrointestinal transit was also reduced by PLS treatment via a cholinergic mechanism. Regarding the diarrhoea caused by CT, PLS reduced all study parameters, and the ELISA showed that PLS can interact with both the GM1 receptor and CT. These results show that PLS from G. caudata effectively improved the parameters observed in acute and secretory diarrhoea, which affects millions of people, and may lead to the development of a new alternative therapy for this disease.