RESUMO
This study aimed to understand the effects of freshwater acidification, driven by industrial runoff, agricultural activities, and atmospheric deposition, on the freshwater mollusk Bellamya bengalensis. By systematically investigating the impact of two common carboxylic acids, acetic acid (AA) and benzoic acid (BA), this research employed diverse toxicological, pathological, and ecological assessments. We explored survival predictions through the generic unified threshold model of survival (GUTS-SD), examined oxidative stress responses, and investigated hepatopancreatic alterations. In the experimental design, Bellamya bengalensis were subjected to environmentally relevant sublethal concentrations (10%, 20% LC50) of AA (39.77 and 79.54 mg/l) and BA (31.41 and 62.82 mg/l) over 28 days. Acute toxicity tests revealed increased LC50 values, indicating heightened toxicity with prolonged exposure, particularly due to the greater potency of benzoic acid compared to acetic acid. The GUTS-SD model provided accurate predictions of time-specific effects on populations, presenting long-term exposure (100 days) LC50 values for AA (263.7 mg/l) and BA (330.9 mg/l). Sequentially, the integrated biomarker response (IBR) analysis across study intervals highlighted the 28-day interval as the most sensitive, with GST emerging as the most responsive enzyme to oxidative stress induced by AA and BA. Histopathological and ultrastructural assessments of the hepatopancreas showed severe alterations, including necrosis, vacuolation and disrupted micro-villi, which were especially pronounced in higher BA exposure concentrations. These findings highlight the health and survival impacts of carboxylic acid toxicity on Bellamya bengalensis, emphasizing the need for proactive measures to mitigate acidification in aquatic ecosystems. The broader ecological implications underscore the importance of effective management and conservation strategies to address ongoing environmental challenges.
Assuntos
Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Hepatopâncreas/efeitos dos fármacos , Hepatopâncreas/ultraestrutura , Hepatopâncreas/patologia , Ácidos Carboxílicos/toxicidade , Gastrópodes/efeitos dos fármacos , Ácido Acético/toxicidade , Ácido Benzoico/toxicidade , Testes de Toxicidade Aguda , Água Doce/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) which has a global impact on the health care system with its recurrent and incompletely curable characteristics, affects the patients' quality of life. Gilaburu (GB; Viburnum opulus L.) is a fruit with rich polyphenol ingredient which is used ethnobotanically in Türkiye for medicinal purposes (for example, to pass kidney stones, to treat stomach, heart, and liver diseases, hemorrhages, hypertension, ulcers, common cold, tuberculosis, rheumatic and menstrual pain, and diabetes). On the other hand, the effects of GB in the experimental UC model have not been studied. AIM OF THE STUDY: This study aimed to explore the potential antioxidant and anti-inflammatory effects of GB fruit extract in improving acetic acid (AA)-induced UC. MATERIALS AND METHODS: Starting immediately after (AA + GB group) or 1 week before (GB + AA + GB group) the colitis induced by intrarectal AA (5%; v/v) administration, the rats orally received GB (100 mg/kg) once per day for 3 days. The control and AA groups were administered orally saline (1 ml), while the AA + SS group were administered sulfasalazine (SS; 100 mg/kg; orally) as a positive control once per day for 3 days. Distal colonic tissue specimens were obtained for the histological and biochemical [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), chemiluminescence (CL), caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-ß1, smad-3 and cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, interferon (IFN)-γ), measurements] evaluations on the 3rd day. RESULTS: Elevated macroscopic and microscopic damage scores, high tissue wet weight values, increased tissue-associated MPO, MDA, CL, caspase-3, 8-OHdG, cytokines (TNF-α, IL-1ß, IL-6, IL-8), MMP-9, TGF-ß1, smad-3 levels, and decreased GSH values of the AA group were all reversed by GB treatments (AA + GB and GB + AA + GB groups) (p < 0.05-0.001). However, sulfasalazine treatment (AA + SS group) did not change the IL-8, 8-OHdG, MMP-9, and TGF-ß1 measurements significantly. CONCLUSIONS: Gilaburu shows both anti-inflammatory and antioxidant effects against AA-induced colonic damage by suppressing neutrophil infiltration, regulating inflammatory mediators, inhibiting reactive species production, lipid peroxidation, and apoptosis, conserving endogenous antioxidant glutathione, and ameliorating oxidative DNA damage. Since the current ulcerative colitis drugs display limited benefits and adverse side effects, potential therapeutic and/or prophylactic role of gilaburu can be evaluated in ulcerative colitis.
Assuntos
Colite Ulcerativa , Viburnum , Humanos , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Ácido Acético/toxicidade , Ácido Acético/metabolismo , Oxidantes/metabolismo , Caspase 3/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Sulfassalazina/farmacologia , Interleucina-6/metabolismo , Frutas/metabolismo , Interleucina-8/metabolismo , Qualidade de Vida , Colo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Citocinas/metabolismo , Glutationa/metabolismo , Anti-Inflamatórios/efeitos adversosRESUMO
BACKGROUND: Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it's often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear. AIM: To investigate the protective effects of A. japonica on acetic acid-induced GU rats. METHODS: The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1ß (IL-1ß), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms. RESULTS: 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1ß, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways. CONCLUSION: These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.
Assuntos
Atractylodes , Úlcera Gástrica , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Ácido Acético/toxicidade , Atractylodes/química , Atractylodes/metabolismo , NF-kappa B/metabolismo , Interleucina-10 , Inibidor de NF-kappaB alfa , Fator de Crescimento Epidérmico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Receptores ErbBRESUMO
BACKGROUND: Ulcerative Colitis (UC) is a disorder which oxidative stress plays a critical role in its pathogenesis. Empagliflozin (EMPA) is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that has been shown to have anti-inflammatory and antioxidative effects. The aim of this study was to investigate the protective effects of EMPA on acetic acid (AA) induced colitis in rats. METHODS: A total of twenty-four rats were divided into four groups (six animals in each group) as follows: (1) Control group; (2) acetic acid (AA)-induced colitis group (AA); (3) EMPA treatment group (AA + EMPA); (4) Dexamethasone (Dexa) treatment group (AA + Dexa). Animals in pre-treatment groups received EMPA (10 mg/kg, i.p.) or dexamethasone (4 mg/kg, i.p. as reference drug) for four consecutive days before induction of colitis by intra-rectal acetic acid (4% v/v) administration. Twenty-four hours after AA administration, rats were sacrificed and the colon tissues were removed for histopathological and biochemical evaluations. RESULTS: Pretreatment with EMPA significantly decreased colon weight/length ratio (81.00 ± 5.28 mg/cm vs. 108.80 ± 5.51 mg/cm) as well as, macroscopic (2.50 ± 0.57 vs. 3.75 ± 0.25) and histological scores (3.3 ± 0.14 vs. 1.98 ± 0.14) compared to the AA-induced colitis group (p < 0.01). Pretreatment with EMPA significantly reduced malondialdehyde (MDA) (324.0 ± 15.93 vs. 476.7 ± 32.26 nmol/mg p < 0.001) and increased glutathione level (117.5 ± 4.48 vs. 94.38 ± 3.950 µmol/mg, p < 0.01) in comparison to the AA-induced colitis group. Furthermore, a significant increase in catalase (44.60 ± 4.02 vs.14.59 ± 2.03 U/mg, P < 0.01), superoxide dismutase (283.9 ± 18.11 vs. 156.4 ± 7.92 U/mg, p < 0.001), and glutathione peroxidase (10.38 ± 1.45 vs. 2.508 ± 0.37, p < 0.01) activities were observed by EMPA pretreatment when compared to the AA-induced colitis group. These results were in line with those of the reference drug. CONCLUSIONS: It is concluded that EMPA could effectively reduce the severity of tissue injury in experimental colitis. This protective effect may be related to the antioxidative effects of EMPA drug.
Assuntos
Ácido Acético , Colite , Animais , Ratos , Ácido Acético/toxicidade , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Dexametasona/farmacologia , Dexametasona/uso terapêuticoRESUMO
Ulcerative Colitis (UC) is a chronic idiopathic inflammatory bowel disease in which the colon's lining becomes inflamed. Exploring herbal remedies that can recover mucosal damage is becoming popular in UC. The study aims to investigate the probable colo-protective effect of a natural isoflavone, genistein (GEN), and/or a drug, sulfasalazine (SZ), against acetic acid (AA)-induced UC in rats, in addition to exploring the possible underlying mechanisms. UC was induced by the intrarectal installation of 1-2 ml of 5% diluted AA for 24 h. Ulcerated rats were allocated into the disease group and three treated groups, with SZ (100 mg/kg), GEN (100 mg/kg), and their combination for 14 days, besides the control groups. The anti-colitic efficacy of GEN and/or SZ was evidenced by hindering the AA-induced weight loss, colon edema, and macroscopic scores, besides reduced disease activity index and colon weight/length ratio. Furthermore, treatments attenuated the colon histopathological injury scores, increased the number of goblet cells, and lessened fibrosis. Both treatments reduced the up-regulation of INF-γ/JAK1/STAT1 and INF-γ /TLR-4/ NF-κB signaling pathways and modulated the IRF-1/iNOS/NO and IL-6/JAK2/STAT3/COX-2 pathways and consequently, reduced the levels of TNF-α and IL-1ß. Moreover, both treatments diminished oxidative stress, which appeared by reducing the MPO level and elevating the SOD activity, and hindered apoptosis; proved by the decreased immunohistochemical expression of caspase-3. The current findings offer novel insights into the protective effects of GEN and suggest a superior benefit of combining GEN with SZ, over either drug alone, in the UC management.
Assuntos
Colite Ulcerativa , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico , NF-kappa B/metabolismo , Interleucina-6/metabolismo , Ciclo-Oxigenase 2/metabolismo , Genisteína/farmacologia , Receptor 4 Toll-Like/metabolismo , Ácido Acético/toxicidade , Ácido Acético/metabolismo , ColoRESUMO
AIMS: Ulcerative colitis is characterized as a chronic immune-mediated inflammatory condition, affecting the intestinal gastroenteric tissue. Previous studies revealed that Th-17 cells are key players in the pathogenesis of ulcerative colitis. RORγT (Retinoic-acid-receptor-related orphan receptor-gamma T) is a lineage-specific transcription factor of Th-17 cells and thus has a role in their differentiation. Transient inhibition of RORγT has been reported to attenuate the differentiation of Th-17 cells and secretion of interleukin-17 (IL-17). Here, we investigated the efficacy of topotecan in ameliorating ulcerative colitis in rodents, via inhibition of the RORγT transcription factor. MAIN METHODS AND KEY FINDINGS: Experimental ulcerative colitis was induced in rats by intrarectal acetic acid administration. Topotecan attenuated the severity of ulcerative colitis in rats by revoking neutrophils and macrophage infiltration to the colon. It also alleviated diarrhea and rectal bleeding and improved body weight. Further, attenuation of RORγT and IL-17 expression was observed in topotecan treated animals. Levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß in the colon tissue were reduced by topotecan treatment. Significant reduction in malondialdehyde level, elevation of superoxide dismutase (SOD) and catalase activity was observed in the colon tissue of rats treated with topotecan compared to the diseased group. SIGNIFICANCE: This study shows the therapeutic potential of topotecan in attenuating ulcerative colitis in rats probably via inhibition of the RORγT transcription factor and downstream mediators of Th-17 cells.
Assuntos
Colite Ulcerativa , Colite , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Ácido Acético/toxicidade , Topotecan/farmacologia , Interleucina-17/metabolismo , Fatores de Transcrição/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Colo/metabolismo , Colite/induzido quimicamenteRESUMO
The prevalence of the debilitating chronic disease ulcerative colitis (UC) is increasing significantly. Mirabegron is a selective beta-3 adrenergic receptor (ß-3 AR) agonist used to treat an overactive bladder. Previous reports have demonstrated the antidiarrheal effect of ß-3AR agonists. Therefore, the current study aims to investigate the potential symptomatic effects of mirabegron on an experimental colitis model. The effects of oral administration of mirabegron (10 mg/kg) for seven days on rats receiving intra-rectal acetic acid instillation on the sixth day were examined using adult male Wistar rats. Sulfasalazine was utilized as a reference medication. Gross, microscopic, and biochemical observations of the experimental colitis were performed. The quantity and mucin content of goblet cells were found to have significantly decreased in the colitis group. In the colons of rats administered mirabegron, the number of goblet cells and the optical density of its mucin content increased. Mirabegron's ability to increase adiponectin in serum and decrease glutathione, GSTM1, and catalase in the colon may account for its protective effects. In addition, mirabegron decreased the expression of the proteins caspase-3 and NF-κB p65. It also prevented the activation of their upstream signaling receptors TLR4 and p-AKT by acetic acid administration. In conclusion, mirabegron prevented acetic acid-induced colitis in rats, possibly due to its antioxidant, anti-inflammatory, and antiapoptotic properties.
Assuntos
Colite Ulcerativa , Colite , Ratos , Masculino , Animais , Ácido Acético/toxicidade , Ácido Acético/metabolismo , Adiponectina/metabolismo , Adiponectina/farmacologia , Adiponectina/uso terapêutico , Ratos Wistar , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Glutationa/metabolismo , NF-kappa B/metabolismoRESUMO
PURPOSE: The total crude alkaloidal extract of Picralima nitida seeds (PNE) is known to possess anti-inflammatory activity among other therapeutic benefits although its benefits in colitis has not been investigated. The current study therefore seeks to investigate the anti-colitis potential of PNE using acetic acid-induced colitis model in rats. METHODS: Sprague Dawley rats were treated with oral 500 mg/kg sulphasalazine or 30, 100, and 300 mg/kg of PNE daily for 8 days with induction of colitis on the fourth day with acetic acid. Rats were killed 24 h after the last treatment and whole blood was obtained from the jugular vein for hematological analysis and biochemical assays. Colons were extirpated for assessment of macroscopic and histological damage to the colon. RESULTS: Treatment with PNE protected against colonic injury induced with acetic acid by decreasing mucosal ulceration, epithelial erosion, inflammatory cell infiltration, and colonic edema. Thus, PNE preserved mucosal architecture and suppressed goblet cells depletion. Moreover, treatment with PNE was associated with improved hematological parameters and reductions in the expression of serum tumor necrosis factor-alpha, interleukin-1ß, and p38 mitogen-activated protein kinase. Also, PNE treatment exerted antioxidant effects by reducing nitric oxide production and increasing glutathione levels. In addition, PNE inhibited colonic lipid peroxidation by decreasing myeloperoxidase activity and malondialdehyde production. CONCLUSION: It can be concluded that PNE attenuates intestinal oxidative and inflammatory damages following intrarectal acetic acid challenge. Thus, demonstrates potential for use in chronic intestinal inflammatory diseases such as ulcerative colitis.
Assuntos
Colite Ulcerativa , Colite , Ratos , Animais , Ácido Acético/toxicidade , Ratos Sprague-Dawley , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Antioxidantes/efeitos adversosRESUMO
While pain results from the activation of nociceptors following noxious stimuli, mounting evidence links pain- and stress-related responses in mammals. In zebrafish, the activation of hypothalamic-pituitary-interrenal (HPI) axis may also regulate body pigmentation (the camouflage response). Here, we aimed to investigate a putative relationship between pain-, stress-, and camouflage-related parameters in adult zebrafish. To answer this question, we assessed whether intraperitoneal acetic acid injection can activate the HPI axis, measuring whole-body cortisol and the camouflage response as physiological endpoints in the presence or absence of morphine or naloxone, an opioid antagonist. Acetic acid induced a stereotypic circling behavior in the top of the tank, accompanied by abdominal writhing-like response, a specific phenotype that reflects local nociceptive effect. Both whole-body cortisol levels and camouflage response increased in the acetic acid group, while morphine prevented these responses, and naloxone antagonized morphine-induced effects. Moreover, we observed positive correlations between representative behavioral, physiological and skin coloration endpoints, and a "pain index" was proposed to summarize phenotypic profile of zebrafish under different pharmacological manipulations. Collectively, these findings suggest a coordinated activation of pain, camouflage- and stress-related pathways following acetic acid injection in zebrafish. Our data also support that camouflage response represents a novel and relevant biomarker for future probing pain and stress neurobiology, with a robust sensitivity to opioidergic drugs.
Assuntos
Ácido Acético , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Ácido Acético/toxicidade , Ácido Acético/metabolismo , Hidrocortisona/metabolismo , Naloxona/farmacologia , Naloxona/metabolismo , Morfina/toxicidade , Morfina/metabolismo , Dor , Fenótipo , Mamíferos/metabolismoRESUMO
Ulcerative Colitis (UC) is a disease that negatively affects quality of life and is associated with sustained oxidative stress, inflammation and intestinal permeability. Vitamin D and Curcumin; It has pharmacological properties beneficial to health, including antioxidant and anti-inflammatory properties. Our study investigates the role of Vitamin D and Curcumin in acetic acid-induced acute colitis model. To investigate the effect of Vitamin D and Curcumin, Wistar-albino rats were given 0.4 mcg/kg Vitamin D (Post-Vit D, Pre-Vit D) and 200 mg/kg Curcumin (Post-Cur, Pre-Cur) for 7 days and acetic acid was injected into all rats except the control group. Our results; colon tissue TNF-α, IL-1ß, IL-6, IFN-γ and MPO levels were found significantly higher and Occludin levels were found significantly lower in the colitis group compared to the control group (p < 0.05). TNF-α and IFN-γ levels decreased and Occludin levels increased in colon tissue of Post-Vit D group compared to colitis group (p < 0.05). IL-1ß, IL-6 and IFN-γ levels were decreased in colon tissue of Post-Cur and Pre-Cur groups (p < 0.05). MPO levels in colon tissue decreased in all treatment groups (p < 0.05). Vitamin D and Curcumin treatment significantly reduced inflammation and restored the normal histoarchitecture of the colon. From the present study findings, we can conclude that Vitamin D and Curcumin protect the colon from acetic acid toxicity with their antioxidant and anti-inflammatory potential.Brief synopsis: In this study; distal colon, distal ileum, jejunum and serum physiopathology in colitis induced by acetic acid and intestinal permeability were investigated. The roles of vitamin D and curcumin in this process were evaluated.
Assuntos
Colite Ulcerativa , Colite , Curcumina , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Curcumina/uso terapêutico , Curcumina/farmacologia , Antioxidantes/farmacologia , Ácido Acético/toxicidade , Fator de Necrose Tumoral alfa , Interleucina-6 , Vitamina D/efeitos adversos , Ocludina/farmacologia , Qualidade de Vida , Ratos Wistar , Colo , Colite/induzido quimicamente , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , InflamaçãoRESUMO
This study evaluated Acetic acid (AA) and Benzoic acid's (BA) acute and sublethal toxicity by observing mortality, behavioral responses, and changes in the levels of oxidative stress enzymes in Tubifex tubifex. Exposure-induced changes in antioxidant activity (Catalase, Superoxide dismutase), oxidative stress (Malondialdehyde concentrations), and histopathological alterations in the tubificid worms were also noted across exposure intervals. The 96 h LC50 values of AA and BA to T. tubifex were 74.99 and 37.15 mg/l, respectively. Severity in behavioral alterations (including increased mucus production, wrinkling, and reduction in clumping) and autotomy showed concentration-dependent trends for both toxicants. Although histopathological effects also showed marked degeneration in the alimentary and integumentary systems in highest exposure groups (worms exposed to 14.99 mg/l for AA and 7.42 mg/l for BA) for both toxicants. Antioxidant enzymes (catalase and superoxide dismutase) also showed a marked increase of up to 8-fold and 10-fold for the highest exposure group of AA and BA respectively. While species sensitivity distribution analysis revealed T. tubifex as most sensitive to AA and BA compared to other freshwater vertebrates and invertebrates, General Unified Threshold model of Survival (GUTS) predicted individual tolerance effects (GUTS-IT), with slower potential for toxicodynamic recovery, as a more likely pathway for population mortality. Study findings demonstrate BA with greater potential for ecological effects compared to AA within 24 h of exposure. Furthermore, ecological risks to critical detritus feeders like T. tubifex may have severe implications for ecosystem services and nutrient availability within freshwater habitats.
Assuntos
Oligoquetos , Poluentes Químicos da Água , Animais , Catalase/metabolismo , Ecossistema , Ácido Acético/toxicidade , Ácido Acético/metabolismo , Oligoquetos/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Benzoatos/metabolismo , Poluentes Químicos da Água/metabolismoRESUMO
Enteric glial cells (EGCs) play an important role in visceral hypersensitivity associated with irritable bowel syndrome (IBS). Losartan (Los) is known to reduce pain; however, its function in IBS is unclear. The present study aimed to investigate Los's therapeutic effect on visceral hypersensitivity in IBS rats. Thirty rats were randomly divided into control, acetic acid enema (AA), AA + Los low, medium and high dose groups in vivo. EGCs were treated with lipopolysaccharide (LPS) and Los in vitro. The molecular mechanisms were explored by assessing the expression of EGC activation markers, pain mediators, inflammatory factors and angiotensin-converting enzyme 1(ACE1)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis molecules in colon tissue and EGCs. The results showed that the rats in the AA group showed significantly higher visceral hypersensitivity than the control rats, which was alleviated by different doses of Los. The expression of GFAP, S100ß, substance P (SP), calcitonin gene-related peptide (CGRP), transient receptor potential vanilloid 1 (TRPV1), tumor necrosis factor (TNF), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) was considerably increased in colonic tissues of AA group rats and LPS-treated EGCs compared with control rats and EGCs, and reduced by Los. In addition, Los reversed ACE1/Ang II/AT1 receptor axis upregulation in AA colon tissues and LPS-treated EGCs. These results show that Los inhibits ACE1/Ang II/AT1 receptor axis upregulation by suppressing EGC activation, resulting in reduced expression of pain mediators and inflammatory factors, thereby alleviating visceral hypersensitivity.
Assuntos
Síndrome do Intestino Irritável , Losartan , Animais , Ratos , Ácido Acético/toxicidade , Enema , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Losartan/farmacologia , Losartan/uso terapêutico , Neuroglia , Dor/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Peptidil Dipeptidase A/metabolismoRESUMO
In traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.
Assuntos
Anacardiaceae , Colite , Humanos , Ratos , Animais , Ácido Acético/toxicidade , Mediadores da Inflamação , Ratos Wistar , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo/patologia , Antioxidantes/farmacologia , Citocinas , Inflamação , Anacardiaceae/químicaRESUMO
Neurobehavioral deficits have been severally reported as a comorbid outcome in inflammatory bowel diseases (IBDs). This study evaluated neurological changes in the experimental model of IBDs, as well potential protective effects of methyl jasmonate (MJ). The study used the acetic acid model of colitis and thereafter delayed the healing process by the administration of indomethacin (Indo) (2 mg/kg, SC). Thirty male Wistar rats (120-160 g) were divided into 5 groups (n = 6). Control, Colitis, Colitis + Indo, MJ (50 mg/kg, IP) + Colitis and MJ + Colitis + Indo. Colitis was induced by intrarectal administration of 2 mL, 4% acetic acid. Neurobehavioral studies were carried out to assess memory function, depression, and anxiety on day 7 of post-colitis induction. Animals were thereafter sacrificed to collect the brain tissues for routine histology, immunoreactivity of GFAP and IBA-1, and biochemical assays. Neurobehavioral tests showed anxiety, depression, and memory deficits, especially in the Colitis + Indo group which were accompanied by increased IBA-1 and GFAP count. MJ reversed these effects and reduced GFAP count in the hippocampus and amygdala as well as IBA-1 count in the hippocampus, amygdala, and cortex. Histological observations of these areas showed no significant histopathological changes across all groups. GPx and CAT levels were significantly reduced, while MPO was significantly increased in colitis and Colitis+indo groups when compared with control, which was attenuated in groups administered with MJ. These findings tuggest that MJ possesses neuroprotective, anti-oxidant, and neuron-regeneration properties. Therefore, it could be considered as a potential treatment for behavioral deficits associated with ulcerative colitis.
Assuntos
Colite Ulcerativa , Colite , Fármacos Neuroprotetores , Animais , Masculino , Ratos , Ácido Acético/toxicidade , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Colite/induzido quimicamente , Colite/patologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos WistarRESUMO
BACKGROUND: It was aimed to induce a new experimental colitis model by using acetic acid and trinitrobenzene sulphonic acid together and to investigate the severity of inflammation biochemically and histopathologically in comparison with other models. METHODS: Fifty-six Wistar albino male rats were randomly divided into 4 groups as control, acetic acid, trinitrobenzene sulphonic acid, and combined groups, and the animals were sacrificed following the induction of colitis on the third day and on the seventh day. The serum amyloid A and myeloperoxidase were tested in plasma samples, and the tumor necrosis factor-alpha, interleukin 33, and ST2 were assayed in colon tissue samples with enzyme-linked immunosorbent assay in addition to histopathological examination. RESULTS: There were statistically significant differences between the combined and the control groups both on the third day and on the seventh day in all parameters. There was no difference between the acetic acid group on the seventh day and the control groups in biochemical parameters. CONCLUSIONS: The acetic acid model forms acute colitis. The combined model is found to be more successful in forming inflammation when compared to other models.
Assuntos
Colite , Colo , Ratos , Animais , Ratos Wistar , Colo/patologia , Ácido Acético/toxicidade , Ácido Trinitrobenzenossulfônico/toxicidade , Colite/induzido quimicamente , Colite/patologia , Fator de Necrose Tumoral alfa , Inflamação/patologia , PeroxidaseRESUMO
BACKGROUND: Cellular inflammatory processes, fibrogenesis, and apoptosis are the most characteristic pathologic features of colonic injury and colitis in human and experimental animals. Obestatin, a peptide derived from proghrelin, is reported to have significant protective and curative actions on many gastrointestinal tract inflammatory diseases, including ulcerative colitis. However, its exact protective mechanisms and the associated histopathological changes, are still in need of deeper exploration. This study explores the effect of obestatin on the course of acetic acid (AA)-induced colitis as an antifibrotic, anti-inflammatory, and anti-apoptotic agent in relation to associated tissue stress parameters. MATERIALS AND METHODS: A total of 40 healthy male albino Wistar rats weighing 200-250 g were recruited in this study. The rats were classified into four groups (10 rats each); group I: control, group II: obestatin only treated (16 nmol/kg), group III: colitis induced group (AA 1 mL of 3.5% (v/v), and group IV: AA-induced colitis + obestatin for 14 days. Colonic samples were examined after staining haematoxylin and eosin, Alcian blue, Masson trichrome. The expression of proliferating cell nuclear antigen (PCNA), nuclear factor kappa B (NFkB), and caspase-3 was estimated after immunohistochemical staining. Oxidative stress parameters, antioxidant enzymes, tissue myeloperoxidase (MPO) activity, ghrelin, and fibrogenesis markers were identified by immunoassay and colorimetric techniques. RESULTS: Colonic mucosa of group IV exhibited mucosal healing and regeneration of the surface epithelium with the restoration of the goblet cells' function together with a decline in PCNA, NFkB, and caspase-3 immunoreactivity in comparison to group III. This was accompanied by a reduction of the expression of fibrosis markers, hydroxyproline and fibronectin. In addition, tissue antioxidant status was significantly improved with a marked reduction of tissue MPO. Ghrelin level was significantly increased in comparison to group III. Group IV exhibited significant reduction in the levels of oxidative stress markers, malondialdehyde, total oxidant status with a marked increase in the activity of antioxidant enzymes, superoxide dismutase, catalase, and total cellular total antioxidant capacity. CONCLUSIONS: The concomitant treatment of obestatin inhibits the development of AA-induced colitis. The data signify that it has both curative and protective effects via antifibrotic, antioxidant, and anti-inflammatory activities.
Assuntos
Antioxidantes , Colite , Humanos , Masculino , Ratos , Animais , Antioxidantes/farmacologia , Grelina/farmacologia , Caspase 3 , Antígeno Nuclear de Célula em Proliferação/uso terapêutico , Ácido Acético/toxicidade , Ácido Acético/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Ratos Wistar , Anti-Inflamatórios/efeitos adversosRESUMO
This study compared the toxicity of raw Bupleuri Radix(BR) and vinegar-processed Bupleuri Radix(VPBR) based on proton nuclear magnetic resonance(~1H-NMR), and explored the mechanism of toxicity. Thirty-two male Sprague-Dawley(SD) rats were randomly divided into four groups: a control group(distilled water), a raw BR group(15 g·kg~(-1)·d~(-1)), a rice VPBR(R-VPBR) group(15 g·kg~(-1)·d~(-1)), and a shanxi VPBR(S-VPBR) group(15 g·kg~(-1)·d~(-1)). After administration for 30 d, pathological sections were treated and observed, and biochemical indexes related to liver and renal function were determined. The serum, liver, and kidney of rats were collected and analyzed by ~1H-NMR. The principal component analysis(PCA) and orthogonal partial least squares-discrimination analysis(OPLS-DA) were performed. The results showed that, as compared with the control group, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase(ALP) in the raw BR group were increased significantly, while ALT and ALP in the R-VPBR and S-VPBR groups were significantly decreased(P<0.05), which indicated that BR showed certain hepatotoxicity, and vinegar processing reduced its hepatotoxicity. No significant difference of blood urea nitrogen(BUN) and creatinine(CREA), the biochemical indexes related to renal function, was observed in the control group and administration groups, indicating that BR had less effect on the renal function. The results of multivariate statistical analysis showed that the biomarkers of BR affecting liver metabolism were methionine, glutamine, and glutamic acid, and affecting kidney metabolism were taurine, ornithine, and inosine. These biomarkers were mainly involved in amino acid metabolism, energy metabolism, lipid metabolism, and taurine metabolism. VPBR alleviated the effect on the biomarkers, and S-VPBR had smaller effect than R-VPBR. Combining the results of biochemical indexes and metabolomics analysis, both raw BR and VPBR showed toxic effect on rats, whereas vinegar processing reduced its toxicity. S-VPBR has smaller effect on kidney and liver metabolism than R-VPBR, which indicates that the vinegar used for processing has certain effect on the toxicity of BR.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Masculino , Ratos , Animais , Ácido Acético/toxicidade , Ácido Acético/química , Medicamentos de Ervas Chinesas/química , Espectroscopia de Prótons por Ressonância Magnética , Ratos Sprague-Dawley , Metabolômica/métodos , Fígado , Doença Hepática Induzida por Substâncias e Drogas/patologia , Taurina/farmacologiaRESUMO
Gastric ulcer (GU) is a peptic disease with high morbidity and mortality rates affecting approximately 4% of the population throughout the world. Current therapies for GU are limited by the high relapse incidence and side effects. Therefore, novel effective antiulcer drugs are urgently needed. Ginsenosides have shown good anti-GU effects, and the major intestinal bacterial metabolite of ginsenosides, protopanaxatriol (PPT), is believed to be the active component. In this study, we evaluated the anti-GU effect of PPT in rats in an acetic acid-induced GU model. High (H-PPT) and medium (M-PPT) doses of PPT (20.0 and 10.0 mg/mg/day) significantly reduced the ulcer area and the ET-1, IL-6, EGF, SOD, MDA and TNF-α levels in serum were regulated by PPT in a dose-dependent manner. We also investigated the mechanisms of anti-GU activity of PPT based on metabolomics coupled with network pharmacology strategy. The result was that 16 biomarkers, 3 targets and 3 metabolomic pathways were identified as playing a vital role in the treatment of GU with PPT and were further validated by molecular docking. In this study, we have demonstrated that the integrated analysis of metabolomics and network pharmacology is an effective strategy for deciphering the complicated mechanisms of natural compounds.
Assuntos
Ginsenosídeos , Úlcera Gástrica , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Ácido Acético/toxicidade , Ginsenosídeos/uso terapêutico , Fator de Necrose Tumoral alfa , Simulação de Acoplamento Molecular , Interleucina-6/efeitos adversos , Fator de Crescimento Epidérmico/efeitos adversos , Farmacologia em Rede , Metabolômica , Biomarcadores , Superóxido DismutaseRESUMO
Moringa oleifera decoction is believed to alleviate gastrointestinal tract diseases. This study investigated antioxidant and anxiolytic activities of its leaves aqueous extract on acetic acid-induced colitis in rats. Rats (36) were randomly divided into six groups and received (20 days) distilled water, 10 mL/kg; Moringa oleifera leaf-aqueous extract (25, 50, and 100 mg/kg) or Loperamide (5 mg/kg). On days 1, 8, 17, and 20, behavioral parameters were evaluated. Colitis was induced (day 15, except in normal group) through acetic acid (4%, 1 mL) intra-rectal administration. After sacrifice (day 21), lesion number, weight/length ratio of the colon were recorded. Oxidative stress biomarkers were evaluated. On day 20, Moringa oleifera (100 mg/kg) reduced the number of head dipping and the duration in opened arms, respectively 2.00 ± 0.37 and 5.00 ± 0.37 s against 14.50 ± 0.72 and 2.17 ± 0.48 s in the control. It decreased colon weight/length ratio: 112.29 ± 9.46 against 185.93 ± 5.28 mg/cm in the control; malondialdehyde level (P < 0.01) and nitric oxide concentration (P < 0.001), in the brain: respectively 25.60 ± 0.60 and 36.34 ± 1.19 against 34.00 ± 0.33 and 46.17 ± 3.25 µmol/mg of tissue in the control. In the serum, the extract (50 mg/kg) significantly (P < 0.05) increased the catalase activity (0.10 ± 0.00 against 0.03 ± 0.00 µmol/mg of protein in the negative control group). At 100 mg/kg, it increased (P < 0.001) reduced glutathione concentration to 5.07 ± 0.31 against 3.26 ± 0.08 µmol/mg of protein in the negative control group. The improvement on colitis pathophysiology, the antioxidant and the anxiolytic effects noted therefore suggest that Moringa oleifera can be a potential source of drugs alleviating anxiety and oxidative stress associated to ulcerative colitis.
Assuntos
Ansiolíticos , Moringa oleifera , Ácido Acético/toxicidade , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Colo/metabolismo , Glutationa/farmacologia , Inflamação , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Água/farmacologiaRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is characterized with chronic inflammation of gastrointestinal track. In the pathogenesis of IBD, inflammation is the main mechanism. Induction of inflammation triggers the oxidative stress that subsequently leading to apoptosis. Considering the all pathological mechanisms, many therapeutic agents have been used for IBD but because of serious side effects there is still a need for new therapeutic drugs. In this study, we aim to evaluate the possible protective effects of Theranekron (TH) on acetic acid (AA)- induced colonic damage and to describe the probable effect mechanisms of TH. MATERIALS AND RESULTS: Fourty female adult Wistar albino rats were divided into 5 groups. Following 24 h fasting, colitis was induced by rectal instillation of AA. In TH group, a single dose of subcutaneous 0.2 ml TH was used. In treatment groups, 0.2 ml TH single dose or 100 mg/kg sulfasalazine (SS) for 7 days were used after colitis induction. Normal salin was used for all applications in control group. Histopathologically hemorrhage, edema and inflammatory reactions were seen in AA group. TH and SS decreased the severity of lesions. Nuclear factor kappa B, Serum amyloid A, C-reactive protein, Growth-related oncogene, and Osteopontin expressions were markedly increased in AA group and TH markedly reduced these expressions. In Western analysis, decreased NF-kB and caspase-3 levels were observed with TH. Oxidative markers did not changed significantly. CONCLUSIONS: TH has a prominent anti-inflammatory effect on AA-induced colonic inflammation via NF-kB signaling whereas antiapoptic effects seem to be independent from this pathway.