Diarrhea In Rats Research Articles

Antidiarrheal, anti-inflammatory and antioxidant effects of Anethum graveolens L. fruit extract on castor oil-induced diarrhea in rats.

Between food and medicine, nutraceuticals are widely used in human health for the prevention and treatment of various diseases. This study aims to determine the cytoprotective effects of Anethum gravelons fruit extract (AGFAE) on castor oil-induced diarrhea in rats due to its phytochemical and antioxidant properties. Male rats were divided into six groups of six animals each: Control (C), Castor oil (CO), CO + different doses of AGFAE (50, 100, and 200 mg/kg, b.w., p.o.), and the CO + loperamide group (LOP, 10 mg/kg, b.w., p.o.). In vitro, the chemical composition of aqueous Dill fruit extract showed strong antioxidant activity, with a high content of total polyphenols, flavonoids, and tannins. In our invivo studies, pre-treatment with AGFAE reduced malondialdehyde and hydrogen peroxide levels and maintained normal activity of enzymatic and non-enzymatic antioxidants in the gastric and intestinal mucosa. In addition, we found that AGFAE prophylaxis improved the stability of many plasma biochemical parameters altered by castor oil intoxication, such as C-reactive protein concentrations and alkaline phosphatase activities. We suggest that AGFAE phenolic compounds had significant protection against diarrhea involving several mechanisms such as reducing hypersecretion, peristaltic, inflammation, and preserving the endogenous antioxidant levels.

Risk assessment of small organoarsenic species in food.

The European Commission asked EFSA for a risk assessment on small organoarsenic species in food. For monomethylarsonic acid MMA(V), decreased body weight resulting from diarrhoea in rats was identified as the critical endpoint and a BMDL10 of 18.2 mg MMA(V)/kg body weight (bw) per day (equivalent to 9.7 mg As/kg bw per day) was calculated as a reference point (RP). For dimethylarsinic acid DMA(V), increased incidence in urinary bladder tumours in rats was identified as the critical endpoint. A BMDL10 of 1.1 mg DMA(V)/kg bw per day (equivalent to 0.6 mg As/kg bw per day) was calculated as an RP. For other small organoarsenic species, the toxicological data are insufficient to identify critical effects and RPs, and they could not be included in the risk assessment. For both MMA(V) and DMA(V), the toxicological database is incomplete and a margin of exposure (MOE) approach was applied for risk characterisation. The highest chronic dietary exposure to DMA(V) was estimated in 'Toddlers', with rice and fish meat as the main contributors across population groups. For MMA(V), the highest chronic dietary exposures were estimated for high consumers of fish meat and processed/preserved fish in 'Infants' and 'Elderly' age class, respectively. For MMA(V), an MOE of ≥ 500 was identified not to raise a health concern. For MMA(V), all MOEs were well above 500 for average and high consumers and thus do not raise a health concern. For DMA(V), an MOE of 10,000 was identified as of low health concern as it is genotoxic and carcinogenic, although the mechanisms of genotoxicity and its role in carcinogenicity of DMA(V) are not fully elucidated. For DMA(V), MOEs were below 10,000 in many cases across dietary surveys and age groups, in particular for some 95th percentile exposures. The Panel considers that this would raise a health concern.

Evaluation of the feeding safety of Moringa (Moringa oleifera L.) in the Sprague Dawley rat

This study aimed to evaluate the safety of Moringa by comparing the effects of different gavage doses of Moringa. The general behavior, body weight, food intake, blood indexes, serum biochemical indexes, and histopathology of rats were used to determine the safety threshold and to provide a reference for the further development and use of Moringa as animal feed. 40 Sprague Dawley rats were selected and given transoral gavage for 28 consecutive days. The T1, T2 and T3 groups were observed for general behavior, body weight, and food intake. Blood and serum biochemical indices were quantified, and histopathology was performed to evaluate the effect and safety of Moringa. The results of the toxicological test showed that (1) Only T1 groups experienced diarrhea. (2) The body weight and food intake of rats in each group were normal compared with the control group. (3) The hematological and serum biochemical indices of rats in the T1 group were significantly different from those of CK but were in the normal range; (4) The results of microscopic examination of the heart, liver, spleen, lung, and kidney of rats in each group were normal, but inflammation occurred in stomach and jejunum of rats in the T1 group, but not in the ileum. The gastrointestinal tract of rats in the T2 and T3 groups were normal. (5) No abnormal death occurred in any of the treatment groups.The results of this study revealed that gavage of Moringa homogenate at a dose of 6 g/kg BW can cause diarrhea in rats. Although there is no pathological effect on weight, food intake, blood and serum biochemical indicators in rats, there are pathological textures in the gastrointestinal tissue caused by diarrhea. Therefore, the safety threshold of Moringa homogenate should be ≤ 3 g/kg BW.

Protective effect of Broussonetia papyrifera leaf polysaccharides on intestinal integrity in a rat model of diet-induced oxidative stress

This study aimed to investigate the effect of Broussonetia papyrifera polysaccharides (BPP) on the jejunal intestinal integrity of rats ingesting oxidized fish oil (OFO) induced oxidative stress. Polysaccharides (Mw 16,956 Da) containing carboxyl groups were extracted from Broussonetia papyrifera leaves. In vitro antioxidant assays showed that this polysaccharide possessed antioxidant capabilities. Thirty-two male weaned rats were allocated into two groups orally infused BPP solution and PBS for 26 days, respectively. From day 9 to day 26, half of the rats in each group were fed food containing OFO, where the lipid peroxidation can induce intestinal oxidative stress. OFO administration resulted in diarrhea, decreased growth performance (p < 0.01), impaired jejunal morphology (p < 0.05) and antioxidant capacity (p < 0.01), increased the levels of ROS and its related products, IL-1β and IL-17 (p < 0.01) of jejunum, as well as down-regulated Bcl-2/Bax (p < 0.01) and Nrf2 signaling (p < 0.01) of jejunum in rats. BPP gavage effectively alleviated the negative effects of OFO on growth performance, morphology, enterocyte apoptosis, antioxidant capacity and inflammation of jejunum (p < 0.05) in rats. In the oxidative stress model cell assay, the use of receptor inhibitors inhibited the enhancement of antioxidant capacity by BPP. These results suggested that BPP protected intestinal morphology, thus improving growth performance and reducing diarrhea in rats ingesting OFO. This protective effect may be attributed to scavenging free radicals and activating the Nrf2 pathway, which enhances antioxidant capacity, consequently reducing inflammation and mitigating intestinal cell death.

In-Vivo Antidiarrhoea Evaluations of Methanol Leaf Extract and Fractions of Chrysophyllum albidum

Background and Objectives: In Nigeria, traditional use of medicinal plants, like Chrysophyllum albidum, for diarrhoea persists. This study assessed its effectiveness in treating diarrhoea in rats. Methods: Extract and Fractions from the plant were tested for antidiarrhoea effect. The process involved methanol extraction and fractionation using hexane, ethyl acetate, and butanol. Rat models were used to evaluate the effects on castor oil-induced diarrhoea, enteropooling, and gastrointestinal motility. Results: Defecation caused by castor oil-induced diarrhoea was inhibited significantly by 53.55, 78.48 and 74.69 % at 500 mg/kg of methanol extract, ethyl acetate, and n-hexane fraction respectively, and by 50.99 and 63.69 % at 250 and 500 mg/kg of butanol fraction respectively. The volume of intestinal content and weight of intestinal content were reduced by 76.74 and 80 % at 500 mg/kg of ethyl acetate fraction. Also, the volume of intestinal content and weight of intestinal content were reduced by 70.93 and 70.83 % at 500 mg/kg of n-hexane fraction. At 250 and 500 mg/kg, the ethyl acetate fraction inhibited intestinal motility by 58.65% and 76.50% respectively. The n-hexane fraction at 500 mg/kg showed a 66.35% inhibition. Conclusion: These fractions from Chrysophyllum albidum leaves exhibit potential antidiarrhoea compounds, as evidenced across all three study models. Ongoing research aims to isolate these compounds for further investigation.

Beneficial effects of the multi-strain probiotic preparation bacimix on antibiotic-associated diarrhea in rats

Dysbiosis is a common status of intestinal microbiota in modern society and is associated with many diseases. Diarrhea is a kind of dysbiosis and is frequently caused by imbalanced gut microbiota due to misuse of antibiotics. A lot of evidence has shown that probiotics can exhibit potential to alleviate the effects of antibiotic-associated diarrhea (AAD). In this study, Lincomycin was utilized to induce AAD in rats and then the effects of the multi-strain probiotic preparation BaciMix on this model were evaluated. The rat groups, including healthy control rats, AAD-induced rats, AAD rats with no treatment (self-healing rats), and AAD rats treated by BaciMix preparation, were analyzed regarding general health status, some immune indices, and intestinal microbiota changes. The results disclosed that the BaciMix preparation remarkably reduced the effects of the antibiotic regarding the diarrhea score and cecum thickness in the rats treated by BaciMix preparation. Additionally, the BaciMix preparation reduced pre-inflammatory cytokines, including TNF-α, and IL-6, while increasing the IgA in sera and intestinal mucosae. Moreover, the BaciMix preparation amended the compositions and differential abundance of intestinal bacteria of the rats to increase some beneficial bacteria like Lactobacillus, Bacillus, Hungatella, and Romboutsia, and to decrease some potentially harmful genera such as Bacteroides, Escherichia-Shigella, and Proteus. Generally, BaciMix preparation displayed helpful effects on the AAD rat model.

Protective effect of Pediococcus pentosaceus Li05 on diarrhea-predominant irritable bowel syndrome in rats.

Pediococcus pentosaceus Li05 (Li05) has demonstrated potential benefits in various intestinal and liver diseases, but its potential and mechanisms in relieving diarrhea have not been understood. The objective of this research was to examine the effects and mechanisms of Li05 in rats with diarrhea-predominant irritable bowel syndrome (IBS-D) induced by wrap restrain stress (WRS) and 4% acetic acid. The results demonstrated that Li05 effectively alleviated weight loss, visceral sensitivity and diarrhea in rats with IBS-D. It also improved intestinal and systemic inflammation by reducing the levels of chemokines and proinflammatory cytokines (GRO/KC, RANTES, IL-1β, IL-7, and IL-18). The 5-hydroxytryptamine (5-HT) signaling pathway is involved in regulating excessive intestinal motility and secretion in IBS-D. Li05 effectively reduced the expression levels of the 5-HT3B receptor (5-HT3BR) (p < 0.01) in the intestine. Additionally, Li05 intervention had a regulatory effect on the gut composition, with a decrease in the abundance of [Ruminococcus] gauvreauii group, Dubosiella, Erysipelatoclostridium and Blautia, and an increase in the abundance of Alloprevotella, Anaerotruncus and Mucispirillum. Furthermore, Li05 induced significant changes in fatty acid and amino acid metabolism in the gut of rats with IBS-D. These findings indicate that Li05 exhibits an effective improvement in IBS-D symptoms by reducing inflammation and modulating gut microbiota and metabolism. Based on the above results, Li05 holds promise as a potential probiotic for managing IBS-D.

Effects of Dietary Allitol and D-Allulose on Body Fat Accumulation and Cecal Short-Chain Fatty Acid Production in Rats Fed a High-Fat Diet.

We investigated the effects of a single and simultaneous intake of allitol and d-allulose on body fat accumulation and cecal short-chain fatty acid (SCFA) production and accurately assessed the contribution of rare sugars to body fat in rats fed a high-fat diet that led to obesity. Thirty-two male 3-week-old Wistar rats were randomly divided into four groups: control, allitol, d-allulose, and allitol + d-allulose. The rats were fed experimental diets and water ad libitum for 11 weeks. High doses of allitol or d-allulose can induce diarrhea in rat; hence, each group of rats was acclimated to 1-5% allitol and d-allulose incrementally for the initial 20 days. After the feeding period, all rats were euthanized and collected tissues. Perirenal, mesenteric, and total intra-abdominal adipose tissue weights were significantly reduced by dietary d-allulose, whereas dietary allitol tended to decrease these adipose tissue weights. Both allitol and d-allulose significantly decreased carcass and total body fat mass. We confirmed that both dietary allitol and d-allulose inhibited body fat accumulation; however, d-allulose did not inhibit hepatic lipogenesis and no synergy was observed between dietary allitol and d-allulose in terms of anti-obesity effects. Dietary allitol significantly increased cecal SCFA levels and these effects were more potent than those of dietary d-allulose. The antiobesity effect of allitol may be due to the action of SCFAs, especially butyric acid, produced by the gut microbiota. Many of the effects of allitol as an alternative sweetener remain unknown, and further research is required.

Fisetin Treats Kidney Oxidative Stress, Inflammation, and Apoptosis in Rat Diarrhea.

Diarrhea is the increase in the excretion of human water; meanwhile, fisetin, a bioactive flavonol molecule, is widely used in the treatment/prevention of gastrointestinal disorders. The purpose of this study is to investigate the anti-diarrheal activity of fisetin by restoring kidney function, antioxidant activity, inflammatory markers, Na+/K+-ATPase level, apoptosis, and protein content in diarrheal rats. A total of 36 male rats were distributed into two groups (18 rats/group): normal and diarrheal. The normal group was further divided into three subgroups (6 rats/subgroup): Control, fisetin, and desmopressin drug subgroups, consisting of normal rats orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively. A lactose diet containing 35% lactose was fed to the normal rats for a month. The diarrheal rats were also divided into three subgroups (6 rats/subgroup): diarrheal rats, diarrheal rats + fisetin, and diarrheal rats + desmopressin drug groups, whereby the diarrheal rats were orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively. Fisetin significantly decreased serum urea (41.20 ± 2.6-29.74 ± 2.65), creatinine (1.43 ± 0.05-0.79 ± 0.06), and urinary volume (1.30 ± 0.41-0.98 ± 0.20), while significantly increasing kidney weight (0.48 ± 0.03-0.67 ± 0.07), sodium, potassium, and chloride balance in both serum and urine. Fisetin significantly increased the antioxidant activity (superoxide dismutase (1170 ± 40-3230 ± 50), glutathione peroxidase (365 ± 18-775 ± 16), catalase (0.09 ± 0.03-0.14 ± 0.06), and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity (8.6 ± 1.31-10.5 ± 1.25), while significantly decreasing malondialdehyde (19.38 ± 0.54-9.54 ± 0.83), conjugated dienes (1.86 ± 0.24-1.64 ± 0.19), and oxidative index (0.62 ± 0.04-0.54 ± 0.05)), alongside the inflammatory markers (tumor necrosis factor-α (65.2 ± 2.59-45.3 ± 2.64), interleukin-1β, interleukin-6 (107 ± 4.5-56.1 ± 7.2), and interleukin-10) in the diarrheal rats to values approaching the control values. Fisetin also restored the Na+/K+-ATPase level, apoptosis, protein content, and kidney architecture in diarrheal rats to be near the control group. Fisetin treated diarrhea in rats by restoring kidney function, antioxidant activity, inflammatory markers, apoptosis, proteome content, and histology.

Rutin from Begonia roxburghii modulates iNOS and Sep A activity in treatment of Shigella flexneri induced diarrhoea in rats: An in vitro, in vivo and computational analysis

In developing countries, diarrhoea is a major issue of concern, where consistent use of antibiotics has resulted in several side effects along with development of resistance among pathogens against these antibiotics. Since natural products are becoming the treatment of choice, therefore present investigation involves mechanistic evaluation of antidiarrhoeal potential of Begonia roxburghii and its marker rutin against Shigella flexneri (SF) induced diarrhoea in rats following in vitro, in vivo and in silico protocols. The roots of the plant are used as vegetable in the North East India and are also used traditionally in treating diarrhoea. Phytochemically standardized ethanolic extract of B. roxburghii (EBR) roots and its marker rutin were first subjected to in vitro antibacterial evaluation against SF. Diarrhoea was induced in rats using suspension of SF and various diarrhoeagenic parameters were examined after first, third and fifth day of treatment at 100, 200 and 300 mg/kg, p.o. with EBR and 50 mg/kg, p.o. with rutin respectively. Additionally, density of SF in stools, stool water content, haematological and biochemical parameters, cytokine profiling, ion concentration, histopathology and Na+/K+–ATPase activity were also performed. Molecular docking and dynamics simulation studies of ligand rutin was studied against secreted extracellular protein A (Sep A, PDB: 5J44) from SF and Inducible nitric oxide synthase (iNOS, PDB: 1DD7) followed by network pharmacology. EBR and rutin demonstrated a potent antibacterial activity against SF and also showed significant recovery from diarrhoea (EBR: 81.29 ± 0.91% and rutin: 75.27 ± 0.89%) in rats after five days of treatment. EBR and rutin also showed significant decline in SF density in stools, decreased cytokine expression, potential antioxidant activity, cellular proliferative nature and recovered ion loss due to enhanced Na+/K+–ATPase activity, which was also supported by histopathology. Rutin showed a very high docking score of −11.61 and −9.98 kcal/mol against iNOS and Sep A respectively and their stable complex was also confirmed through dynamics, while network pharmacology suggested that, rutin is quite capable of modulating the pathways of iNOS and Sep A. Thus, we may presume that rutin played a key role in the observed antidiarrhoeal activity of B. roxburghii against SF induced diarrhoea.

Phytochemical characterization, anti-diarrhoeal, analgesic, anti-inflammatory activities and toxicity profile of Ananas comosus (L.) Merr (pineapple) leaf in albino rats

Ethnopharmacological relevanceAnanas comosus (pineapple) leaf is used in ethnomedicine to treat diarrhoea, inflammation, pain, bacterial infections and oedema. Aim of the studyThe aim of this study was to investigate the anti-diarrhoeal, anti-inflammatory and analgesic effects as well as the toxicity profile of the aqueous Ananas comosus leaf extract (AACLE) in rats. MethodsMethanol ACLE was subjected to gas chromatography-mass spectrometry (GC-MS) analysis. In the acute toxicity study, a single oral dose of up to 5000 mg/kg AACLE was administered. In the subacute toxicity study (28 days), rats in groups 2–4 received AACLE orally. The anti-diarrhoeal effect was studied using charcoal meal and castor oil-induced diarrhoea. Anti-inflammatory and analgesic tests were measured using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute toxicity, anti-diarrhoeal, analgesic, and anti-inflammatory studies, AACLE was administered orally to rats at doses of 200, 400, and 600 mg/kg body weight. ResultsHexadecanoic acid methyl ester, 2-methoxy-4-vinylphenol, n-hexadecanoic acid and n-heptadecanol-1 were identified among other compounds with known pharmacological activities by GC-MS analysis. No deaths, behavioural changes, or signs of toxicity were observed in the acute toxicity study. Treatment with AACLE (28 days) decreased aspartate aminotransferase, alanine transaminase, total cholesterol, triglycerides, and low-density lipoprotein cholesterol, while high-density lipoprotein cholesterol, glutathione, and catalase increased when compared with control (P < 0.05). Treatment with AACLE did not cause significant changes in haematological or renal function parameters. Treatment with AACLE inhibited gastrointestinal motility and castor oil-induced diarrhoea in rats. Treatment with AACLE resulted in a dose-dependent (200–600 mg/kg) significant (P < 0.05) anti-diarrhoeal, analgesic, and anti-inflammatory effect compared to standard drugs. ConclusionOur study revealed that ACLE is not toxic but contains bioactive compounds with anti-diarrhoeal, anti-inflammatory, antimicrobial, and hepatoprotective activity. AACLE has antidiarrhoeal, analgesic and anti-inflammatory activity in rats, which justifies its therapeutic use in traditional medicine.

Medication adjustment of afatinib and combination therapy with sitagliptin for alleviating afatinib-induced diarrhea in rats

Afatinib, as the first-line treatment for non-small cell lung cancer (NSCLC), causes severe gastrointestinal adverse reactions that greatly affect patients' quality of life and even potentially result in treatment discontinuation. Multiple dose adjustments and concomitant use of anti-diarrheal medications are commonly employed to manage diarrhea, also allowing for a recovery period between each adjustment. However, these approaches are based on empirical guidance and still have limitations. This study aims to explore reliable approaches to alleviate diarrhea by focusing on two strategies: adjusting the dosing regimen of afatinib itself and implementing combination therapy. In this study, we firstly revealed a dose-dependent relationship between afatinib-induced diarrhea and gastrointestinal epithelial damage, resulting in atrophy, reduced expression of tight junction proteins, and increased permeability. We further found that even after discontinuation of the medication, although the severity of diarrhea had improved to baseline, the tight junction proteins and permeability of the intestinal epithelium did not fully recover, and the pharmacokinetics studies showed that drug absorption significantly increased than normal. This indicated the recovery period was longer than expected and may accelerate the occurrence of subsequent episodes of diarrhea. Hence, it would be prudent to consider adjustments to the starting dose or the recovery interval. Furthermore, we initially investigated the relationship between DPP enzyme and afatinib-induced diarrhea and found a significant decrease in plasma DPP enzyme activity following afatinib-induced diarrhea. Subsequently, we conducted continuous treatment with sitagliptin and observed significant improvement in afatinib-induced diarrhea. We observed that sitagliptin can promote the production of anti-inflammatory factors, increase the expression of intestinal epithelial tight junction proteins, and improve intestinal microbiota, further validating the mechanism through the use of GLP-23-33 as GLP-2 receptor inhibitor. In conclusion, sitagliptin exhibits promising potential as a therapeutic option for managing afatinib-induced diarrhea. Taken together, our study provides valuable insights into alleviating afatinib-induced diarrhea through both afatinib medication adjustment and sitagliptin combination therapy.

Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation

ObjectivesJian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. DesignIn this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. MethodsThe rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. ResultsJPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. ConclusionJPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. InnovationIn this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

Anakinra and dexamethasone treatment of idarubicin-induced mucositis and diarrhoea in rats.

Chemotherapy-induced mucositis, characterised by diarrhoea and villous atrophy, is a severe side effect contributing to reduced quality of life and premature death in cancer patients treated with cytostatics. Despite its high incidence, there is no effective supportive therapy available. The main objective of this study was to determine if the anti-inflammatory drugs anakinra and/or dexamethasone - which have different mechanism-of-action - might be used to effectively treat idarubicin-induced mucositis in rats. Mucositis was induced through a single injection with 2 mg/kg idarubicin (with saline as control), followed by daily treatments of anakinra (100 mg/kg/day), dexamethasone (10 mg/kg/day), or both during three days. After 72 hours, jejunal tissue was collected for morphological, apoptotic, and proliferative analyses, and colonic faecal water content and body weight change were determined. The diarrhoea that was induced by idarubicin (from 63.5% to 78.6% water content in faeces) was completely reversed by anakinra alone, and the jejunal villus height reduction by 36% was prevented by a combination of anakinra and dexamethasone. Dexamethasone reduced apoptosis in the jejunal crypts, both alone and in combination with anakinra. These positive effects encourage further investigations into the use of anakinra and dexamethasone as supportive therapies for chemotherapy-induced intestinal mucositis and diarrhoea.

Antibiotic treatment targeting gram negative bacteria prevents neratinib-induced diarrhea in rats

BackgroundNeratinib is a pan-ErbB tyrosine kinase inhibitor used for extended adjuvant treatment of HER2-positive breast cancer. Diarrhea is the main adverse event associated with neratinib treatment. We aimed here to determine whether antibiotic-induced gut microbial shifts altered development of neratinib-induced diarrhea. MethodsFemale Albino Wistar rats (total n = 44) were given antibiotics (vancomycin, neomycin, or a cocktail of vancomycin, neomycin and ampicillin) in drinking water for four weeks, and then treated daily with neratinib (50 mg/kg) for 28 days. Diarrhea, along with markers of gastrointestinal damage and microbial alterations were measured by histopathology and 16S sequencing, respectively. ResultsRats treated with vancomycin or neomycin had significantly lower levels of diarrhea than rats treated with neratinib alone. In the distal ileum, neratinib was associated with a statistically significant increase in histological damage in all treatment groups expect the antibiotic cocktail. Key features included villous blunting and fusion and some inflammatory infiltrate. Differences in microbial composition at necropsy in vehicle control, neratinib and neratinib + neomycin groups, were characterized by a neratinib-induced increase in gram-negative bacteria that was reversed by neomycin. Neomycin shifted bacterial composition so that Blautia become the dominant genus. ConclusionsNarrow spectrum antibiotics reduced neratinib-induced diarrhea. This suggests that the microbiome may play a key role in the development and prolongation of diarrhea following neratinib treatment, although further research is required to understand the key bacteria and mechanisms by which they reduce diarrhea, as well as how this may impact presentation of diarrhea in clinical cohorts.

The Diarrhea Preventive Effect of Lactobacillus fermentum From Dengke Naniura in Rats Induced Escherichia coli

Diarrhea is discharge of abnormal and liquid stool with a frequency of 3-4 daily which caused by pathogenic organisms such as Escherichia coli, and other. Dengke Naniura is a traditional Batak Toba food that can produce probiotics (Lactobacillus fermentum). Probiotics are defined as live microorganisms that confer a health benefit on the host. Nutritional supplements combined between probiotics and prebiotics are called synbiotics, The purpose of this study was to analyze the preventive effect of diarrhea in rats given L.fermentum for 21 days. The preventive effect of diarrhea test begins with the giving of L.fermentum from day 1 to day 21. From day 7 to day 14 rats were induced with E.coli. Weight of the rats, stool consistency, onset of diarrhea, frequency of diarrhea, and duration of diarrhea were observed. The results of the observation that weight of rats in the L.fermentum group increased compared to group 1 (p&lt;0.05). Consistency stool is soft (massless). Onset of diarrhea on day 1 after induced of E.coli in the group 1. Frequency of diarrhea increased to 9.25 ± 0.50 times on day 14 (group 1). And diarrhea occurs for 10 days. Conclusion L.fermentum showed a preventive effect of diarrhea in rats induced E.coli.

Antioxidant Properties, Phytoactive Compounds and Potential Protective Action of Salvia officinalis Flowers Against Combined Gastro-Intestinal Ulcer and Diarrhea Experimentally Induced in Rat.

The present study was conducted to investigate the protective action of Salvia officinalis flowers aqueous extract (SOFAE) against combined gastro-intestinal (GI) disorders-induced by ethanol and castor oil administration in rats. Adult male Wistar rats were divided into seven groups of ten each and various doses of SOFAE (50, 100, and 200 mg kg−1, b.w., p.o.) and sulfasalazine (100 mg kg−1, b.w., p.o.) were daily administrated during 15 days. After, animals were intoxicated with a single oral administration of ethanol (4 g kg−1, b.w., p.o.) and castor oil (5 mL kg−1, b.w., p.o.). We found that SOFAE contains several phytoactive compounds with a strong ABTS scavenging ability. In vivo, we showed that SOFAE protected against EtOH/CO-induced macroscopic and histological alterations in GI tract accompanied by intestinal fluid accumulation and gastric juice decrease. SOFAE significantly counteracted lipoperoxydation increase and reversed the depletion of both enzymatic and non-enzymatic antioxidants. More importantly, SOFAE significantly reduced the levels of inflammatory markers (CRP and ALP) in plasma and mucosal GI tract. In conclusion, our data clearly indicate that the SOFAE exerted a potential protective effect against EtOH-induced peptic ulcer combined with CO-induced diarrhea in rats. These effects could be associated with its antioxidant and anti-inflammatory properties.

Antidiarrheal Activity of Albizzia lebbeck Leaves

Worldwide, more than 5–8 million deaths are caused each year by diarrhea. At present, used anti-diarrheal drugs show adverse effects in some form. Hence, there is a need to explore natural drugs as alternative therapy. Preliminary phytochemical screening, Acute oral toxicity and antidiarrheal activity of 70% ethanolic extract of the Albizzia lebbeck leaves (ALL) were performed. ALL were assessed for antidiarrheal activity using castor oil, Prostaglandin-E2 (PGE2) and intestinal motility induced diarrhea in rats. On the basis of acute oral toxicity, 100 and 200 mg/kg body weight doses were selected for antidiarrheal activity. Preliminary phytochemical screenings revealed presence of flavonoids tannins and saponins in extract. ALL showed significant inhibitory activity against castor oil, PGE2 induced diarrhea and intestinal motility. On the basis of the result, it can be concluded that the ALL possess significant antidiarrheal activity.

Huang Bai Jian Pi decoction alleviates diarrhea and represses inflammatory injury via PI3K/Akt/NF-κB pathway: In vivo and in vitro studies

Ethnopharmacological relevanceHuang Bai Jian Pi (HBJP) decoction, a Chinese herbal formula based on the Pulsatilla decoction (PD) and Si Junzi decoction, is efficacy to treat clinical diarrhea in calves. Aim of the studyThe mechanism of HBJP decoction to treat calf diarrhea remains unclear. This study was to investigate the therapeutic effect and anti-inflammatory mechanism of HBJP decoction on diarrhea in rats. Materials and methodsThirty-six Sprague Dawley rats were randomly divided into control group, model group, PD group and three treated groups with HBJP decoction. The diarrheal model in rats was established by multiple factors including high-sugar and fat diet, high temperature and dampness environment, biological pathogenic factors. The diarrheal animals were treated with HBJP decoction or PD for 5 days. The inflammatory model of the intestinal epithelioid cell line 6 (IEC-6) was induced by TNF-α. The clinical symptoms, blood routine and biochemistry parameters, histopathology of main organs were detected. The proteins associated with PI3K/Akt/NF-κB pathway and the expression levels of cytokines associated with inflammation were detected in vivo and in vitro by Western blot and ELISA. ResultsThe model rats showed obvious diarrheal symptoms, and the obvious systemic inflammatory response accompanied with abnormal change in blood routine, biochemistry parameters and histopathology. HBJP decoction alleviated obviously the clinical symptoms, and pathological changes of the liver, colon and lung, and abnormal blood routine and biochemistry indexes in rats. The expression of P-PI3K, P-Akt, P–NF-κB, IL-1β, IL-6 was significantly increased, and the expression of IL-10 was markedly decreased in diarrheal rats and IEC-6 with inflammation. HBJP decoction significantly inhibited the PI3K/AKT/NF-κB signal pathway and adjusted the expression of these inflammatory cytokines. ConclusionsThe finding suggested that HBJP decoction alleviate the inflammation in diarrhea through inhibiting the PI3K/Akt/NF-κB signal pathway, which provides scientific evidences for the clinical application of HBJP decoction in diarrhea.

Zinc Deficiency Elevates Fecal Protein, But Not Electrolyte and Short-Chain Fatty Acid, Levels in Enterotoxigenic Escherichia coli-Induced Diarrhea in Rats.

PurposeTo determine the effect of zinc deficiency on fecal protein, electrolyte, and short-chain fatty acid levels in both heat-stable (ST) and heat-labile (LT) enterotoxigenic Escherichia coli (ETEC)-induced diarrhea in rats.MethodsAlbino rats, weighing 100 to 150 g, were divided into 2 groups, with 15 animals each: non-zinc and zinc-deficient. These two groups were sub-divided into three sub-groups with five rats each: control (saline); LT-ETEC; and ST-ETEC. Sodium phytate (30 mmol/L) was added to the animals’ water to induce zinc deficiency, while diarrhea was induced using 5×109 ETEC cells/mL. Fecal protein levels were estimated using the Bradford method, while sodium and potassium levels were determined using atomic absorption spectrophotometry. Short-chain fatty acids were measured using gas chromatography-mass spectrometry.ResultsAmong the non-zinc and zinc-deficient groups, there were significant increases (p=0.04), (p=0.03) in fecal protein concentrations (mg/mL) in the LT-ETEC- (4.50±0.33), (6.50±0.26) and ST-ETEC- (3.85±0.19), (5.98±0.32) induced groups compared to the control groups (2.60±0.52), (3.50±0.11) respectively. Fecal sodium and potassium levels (mg/L) were significantly (p=0.029) increased in non-zinc-deficient rats induced with LT-ETEC (9.35±0.95, 1.05±0.48), and ST-ETEC (9.96±1.02, 1.21±0.45) compared with the control group (8.07±0.44, 0.47±0.17) but the increase were not statistically significant (p=0.059) in the zinc deficient rat groups. Fecal acetate and propionate levels (mg/g) significantly (p=0.032) increased when induced with LT-ETEC and ST-ETEC in non-zinc and zinc-deficient groups compared with the control groups.ConclusionZinc deficiency among rats with ETEC-induced diarrhea elevated fecal protein loss but may not have an effect on fecal sodium, potassium and short-chain fatty acid levels.