Objective
The aim of this study was to investigate whether experimental periodontitis cause changes to the renal tissues and imbalance in oxidative stress in kidneys.
Methods
Twenty‐two female Wistar ...rats were separated into two groups: control and periodontitis. We assessed the following parameters: gingival bleeding index (GBI), tooth mobility, gum malondialdehyde (MDA), myeloperoxidase (MPO) activity, probing pocket depth (PPD), alveolar bone loss (ABL) for periodontal tissues; histomorphometric measures associated with renal corpuscle and histopathological aspects (evaluation of brush border) for kidneys; as also blood and urine biomarkers. Finally, we evaluated renal oxidative stress through glutathione (GSH) and MDA respectively.
Results
With regard to renal histomorphometry, significant differences were observed in all parameters assessed. In relation periodic acid Schiff (PAS) staining, disruption was observed of brush border in the periodontitis group in the renal tubules in comparison with the control group. The periodontitis group presented significantly higher MDA and lower GSH concentrations in the kidneys compared with animals without periodontitis.
Conclusion
The induced periodontitis caused histomorphometric changes in renal tissues as well as disruption of the brush border in renal tubules, alterations associated with increase in oxidative stress in kidneys. However, these alterations were not sufficient to cause differences in the renal function markers.
Inflammation is the response of the body to noxious stimuli such as infections, trauma, or injury. Experimental studies have shown that vanillic acid has anti‐inflammatory effects. The objective of ...this study was to investigate the anti‐inflammatory and antipyretic properties of the derivative of vanillic acid, isopropyl vanillate (ISP‐VT), in mice. The results of this study indicated that ISP‐VT reduced paw edema induced by carrageenan, dextran sulfate (DEX), compound 48/80, serotonin, bradykinin (BK), histamine (HIST), and prostaglandin E2 (PGE2). Furthermore, ISP‐VT reduced recruitment of leukocytes and neutrophils and reduced its adhesion and rolling, and decreased myeloperoxidase enzyme activity (MPO), cytokine levels (tumor necrosis factor‐α and interleukin‐6), and vascular permeability. ISP‐VT also significantly reduced the expression of cyclooxygenase‐2 (COX‐2) in subplantar tissue of mice. ISP‐VT inhibited COX‐2 selectively compared to the standard drug. Our results showed that although ISP‐VT binds to COX‐1, it is less toxic than indomethacin, as evidenced by MPO analysis of gastric tissue. Treatment with the ISP‐VT significantly reduced rectal temperature in yeast‐induced hyperthermia in mice. Our results showed that the main mechanism ISP‐VT‐induced anti‐inflammatory activity is by inhibition of COX‐2. In conclusion, our results indicate that ISP‐VT has potential as an anti‐inflammatory and antipyretic therapeutic compound.
This study aimed to evaluate the effect of
DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential ...vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 10⁸ CFU•g body wt
•day
of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 μmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of
parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.
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The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects on the body, especially on the cardiac system and ...gastrointestinal tract. ACE II is responsible for converting Ang II into the active peptide Ang-(1–7), which in turn binds to a metabotropic receptor, the Mas receptor (MasR). Recent studies have demonstrated that Diminazene Aceturate (DIZE), a trypanosomicide used in animals, activates the ACE II pathway. In this study, we aimed to evaluate the antidiarrheal effects promoted by the administration of DIZE to activate the ACE II/Ang-(1–7)/MasR axis in induced diarrhea mice models. The results show that activation of the ACE II pathway exerts antidiarrheal effects that reduce total diarrheal stools and enteropooling. In addition, it increases Na+/K+-ATPase activity and reduces gastrointestinal transit and thus inhibits contractions of intestinal smooth muscle; decreases transepithelial electrical resistance, epithelial permeability, PGE2-induced diarrhea, and proinflammatory cytokines; and increases anti-inflammatory cytokines. Enzyme-linked immunosorbent assay (ELISA) demonstrated that DIZE, when activating the ACE II/Ang-(1–7)/MasR axis, can still interact with GM1 receptors, which reduces cholera toxin-induced diarrhea. Therefore, activation of the ACE II/Ang-(1–7)/MasR axis can be an important pharmacological target for the treatment of diarrheal diseases.
Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and ...investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of M + H
= 1563.8 Da and M + H
= 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.
Intestinal mucositis is an inflammatory process occurring in the intestinal mucosa and is a common side effect of irinotecan hydrochloride (CPT-11) based anticancer regimens. The transient receptor ...potential cation channel, subfamily A, member 1 (TRPA1) receptor is highly expressed in the intestinal mucosa and has the ability to identify cell damage signaling indicates its possible association with intestinal mucositis. Carvacrol is an agonist of the TRPA1 receptor and has anti-inflammatory properties. Thus, the aim of the present study was to verify the supposed anti-inflammatory and protective action of carvacrol via TRPA1 activation against intestinal mucositis induced by CPT-11 in mice. Briefly, mice were treated with either DMSO 2% or CPT-11 (75 mg/kg, per 4 days, i.p.) or the carvacrol (25, 75 or 150 mg/kg, per 8 days, i.p.) before CPT-11. In other group, the animals were pretreated with HC-030031, a TRPA1 antagonist, 30 min before treatment with carvacrol. On day 7, animal survival and bacteremia were assessed, and following euthanasia, samples of the jejunum were obtained for morphometric analysis and measurement of antioxidant and pro-inflammatory markers. Carvacrol was found to exert an anti-inflammatory action against CPT-11-induced intestinal mucositis through strong interactions with TRPA1 receptors; reduction in the production or release or both of pro-inflammatory cytokines (TNF-α, IL-1β, and KC); and decrease in other indicators of inflammation (MPO, NF-κB, COX-2) and oxidative stress (GSH, MDA, and NOx levels). It also contributed to the restoration of the tissue architecture of the villi and crypts in the small intestine, and improved clinical parameters such as survival, body mass variation, leukogram, and blood bacterial count. Thus, TRPA1 could be a target for future therapeutic approaches in the treatment of intestinal mucositis.
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•Carvacrol reduced the production and/or release of inflammatory markers (TNF-α, IL-1β, KC, MPO, NF-κB and COX-2).•Carvacrol reduced the oxidative stress (GSH, MDA, and NOx levels).•CPT-11-induced intestinal mucositis is reversed by carvacrol (↑villi height and crypt depth).•Carvacrol reduces intestinal mucositis by strong interaction with TRPA1 receptors.•TRPA1 could be a target for future therapeutic approaches in the treatment of intestinal mucositis.
Background
It has been reported that simvastatin, a statin commonly prescribed for its anti-inflammatory and antioxidant effects, has gastroprotective effects in indomethacin and ethanol-induced ...gastric ulcers. However, the effects of simvastatin on alendronate-induced gastric mucosal injury remain unexplored.
Aim
This study investigated the use of simvastatin for the treatment of alendronate-induced gastric ulcers in rats.
Methods
Female rats were pretreated with vehicle or simvastatin (20 and 60 mg/kg p.o.). After 1 h, the rats received alendronate (50 mg/kg p.o.). Simvastatin was administered once daily for 7 days, and from the fourth day of simvastatin treatment, alendronate was administered once daily for 4 days. On the final day of treatment, 4 h after alendronate administration, animals were euthanized, their stomachs were removed, and gastric damage was measured. Samples of the stomach were fixed in 10 % formalin immediately after their removal for subsequent histopathological assessment. Unfixed samples were weighed, frozen at −80 °C until assayed for glutathione (GSH), malondialdehyde (MDA), and cytokine levels and myeloperoxidase (MPO) activity. A third group was used to measure mucus and gastric secretion.
Results
Pretreatment with simvastatin prevented alendronate-induced macroscopic gastric damage and reduced the levels of MDA and GSH, TNF-α and IL-1β, MPO activity, and mucus levels, in the stomach.
Conclusions
This study demonstrates the protective effects of simvastatin against alendronate-induced gastric ulceration. Maintenance of mucosal integrity, inhibition of neutrophil activity, and reduced oxidative stress associated with decreased gastric acidity may explain the gastroprotective effects of simvastatin.
Hydrogen sulphide (H2S) is a gasotransmitter that participates in various physiological and pathophysiological processes within the gastrointestinal tract. We studied the effects and possible ...mechanism of action of H2S in secretory diarrhoea caused by cholera toxin (CT). The possible mechanisms of action of H2S were investigated using an intestinal fluid secretion model in isolated intestinal loops on anaesthetized mice treated with CT. NaHS and Lawesson's reagent and l-cysteine showed antisecretory activity through reduction of intestinal fluid secretion and loss of Cl− induced by CT. Pretreatment with an inhibitor of cystathionine-γ-lyase (CSE), dl-propargylglycine (PAG), reversed the effect of l-cysteine and caused severe intestinal secretion. Co-treatment with PAG and a submaximal dose of CT increased intestinal fluid secretion, thus supporting the role of H2S in the pathophysiology of cholera. CT increased the expression of CSE and the production of H2S. Pretreatment with PAG did not reverse the effect of SQ 22536 (an AC inhibitor), bupivacaine (inhibitor of cAMP production), KT-5720 (a PKA inhibitor), and AICAR (an AMPK activator). The treatment with Forskolin does not reverse the effects of the H2S donors. Co-treatment with either NaHS or Lawesson's reagent and dorsomorphin (an AMPK inhibitor) did not reverse the effect of the H2S donors. H2S has antisecretory activity and is an essential molecule for protection against the intestinal secretion induced by CT. Thus, H2S donor drugs are promising candidates for cholera therapy. However, more studies are needed to elucidate the possible mechanism of action.
•Cholera toxin induces an increase in the expression of CSE in mice.•H2S displayed antidiarrheal activity in secretory diarrhoea induced by cholera toxin in mice.•Antisecretory effect of H2S occurs by a mechanism independent of AC/cAMP/PKA and AMPK.•H2S donors have potential in cholera therapy.
Activation of 5′ adenosine monophosphate-activated protein kinase (AMPK) stimulates production of the gaseous mediators nitric oxide (NO) and carbon monoxide (CO), which are involved in mucosal ...defense and gastroprotection. As AMPK itself has gastroprotective effects against several gastric ulcer etiologies, in the present study, we aimed to elucidate whether AMPK may also prevent ethanol-induced injury and play a key role in the associated gastroprotection mediated by hydrogen sulfide (H2S), NO, and CO. Mice were pretreated with AICAR (20 mg/kg, an AMPK activator) alone or with 50% ethanol. Other groups were pretreated with respective gaseous mediator inhibitors PAG, l-NAME, or ZnPP IX 30 min prior to AICAR, or with gaseous mediator donors NaHS, Lawesson's reagent and l-cysteine (H2S), SNP, l-Arginine (NO), Hemin, or CORM-2 (CO) 30 min prior to ethanol with or without compound C (10 mg/kg, a non-selective AMPK inhibitor). H2S, nitrate/nitrite (NO3−/NO2−), bilirubin levels, GSH and MDA concentration were evaluated in the gastric mucosa. The gastric mucosa was also collected for histopathological analysis and AMPK expression assessment by immunohistochemistry. Pretreatment with AICAR attenuated the ethanol-induced injury and increased H2S and bilirubin levels but not NO3−/NO2− levels in the gastric mucosa. In addition, inhibition of H2S, NO, or CO synthesis exacerbated the ethanol-induced gastric damage and inhibited the gastroprotection by AICAR. Pretreatment with compound C reversed the gastroprotective effect of NaHS, Lawesson's reagent, l-cysteine, SNP, l-Arginine, CORM-2, or Hemin. Compound C also reversed the effect of NaHS on H2S production, SNP on NO3−/NO2− levels, and Hemin on bilirubin levels. Immunohistochemistry revealed that AMPK is present at basal levels mainly in the gastric mucosa cells, and was increased by pretreatment with NaHS, SNP, and CORM-2. In conclusion, our findings indicate that AMPK activation exerts gastroprotection against ethanol-induced gastric damage and mutually interacts with H2S, NO, or CO to facilitate this process.
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•AMPK activation has a beneficial effect in the gastroprotection.•AMPK interact with the gaseous mediators H2S, NO, and CO in the gastroprotection.•Gaseous mediator donors increased the AMPK immunoreactivity in gastric tissue.•AMPK interaction with the gaseous mediators has potential in gastritis therapy.
Anacardium occidentale L. (Anacardiaceae) is commonly known as the cashew tree. It is native to tropical America and extracts of the leaves, bark, roots, chestnut net and exudate have been ...traditionally used in northeast Brazil for the treatment of various diseases. The exudate of the cashew tree (cashew gum) has been exploited by locals since ancient times for multiple applications, including the treatment of diarrheal diseases.
The primary aim of the present study is to evaluate the antidiarrheal activity of cashew gum (CG), a complex heteropolysaccharide from the exudate of the cashew tree, using various models.
The antidiarrheal activity of cashew gum (CG) against acute diarrhea was investigated using the castor oil-induced diarrhea model. The effects of CG on gastrointestinal transit and castor oil- and PGE2- induced enteropooling were also examined in rodents. In addition, the effect of CG against secretory diarrhea was investigated using a model of fluid secretion in cholera toxin-treated intestinal closed loops in live mice.
Cashew gum (30, 60, and 90mg/kg, p.o.) showed a significant (P<0.05–0.01) antidiarrheal effect in rats with castor oil-induced diarrhea, inhibiting the total amount of stool and diarrheal stools. The 60mg/kg dose of CG exhibited excellent antidiarrheal activity and significantly reduced the severity of diarrhea (diarrhea scores) in rats. CG (60mg/kg) significantly (P<0.05) decreased the volume of castor oil- and PGE2-induced intestinal fluid secretion (enteropooling). In addition, similar to loperamide (standard drug, 5mg/kg, p.o.), CG treatment reduced the distance traveled by a charcoal meal in the 30-min gastrointestinal transit model by interacting with opioid receptors. In cholera toxin-induced secretory diarrhea, CG (60mg/kg) significantly inhibited the intestinal fluid secretion and decreased Cl− ion loss in the cholera toxin-treated isolated loops model of live mice by competitively binding to cholera toxin-GM1 receptors.
In conclusion, our results indicate that a complex heteropolysaccharide extracted from the exudate of A. occidentale L. has antidiarrheal activity in acute, inflammatory, and secretory diarrhea models, which could justify its traditional use in the treatment of diarrhea in northeast Brazil. The antidiarrheal activity might be explained by the capacity of CG to inhibit gastrointestinal motility and thereby reduce the accumulation of intestinal fluid and the secretion of water and chloride ions in the lumen of the intestine.
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