Comprehensive analysis of gastrointestinal side effects in COVID-19 patients undergoing combined pharmacological treatment with azithromycin and hydroxychloroquine: a systematic review and network meta-analysis.

During the COVID-19 pandemic, several drugs were repositioned and combined to quickly find a way to mitigate the effects of the infection. However, the adverse effects of these combinations on the gastrointestinal tract are unknown. We aimed investigate whether Hydroxychloroquine (HD), Azithromycin (AZ), and Ivermectin (IV) used in combination for the treatment of COVID-19, can lead to the development of gastrointestinal disorders. This is a systematic review and network meta-analysis conducted using Stata and Revman software, respectively. The protocol was registered with PROSPERO (CRD42023372802). A search of clinical trials in Cochrane Library databases, Embase, Web of Science, Lilacs, PubMed, Scopus and Clinicaltrials.gov conducted on November 26, 2023. The eligibility of the studies was assessed based on PICO criteria, including trials that compared different treatments and control group. The analysis of the quality of the evidence was carried out according to the GRADE. Six trials involving 1,686 COVID-19 patients were included. No trials on the association of HD or AZ with IV met the inclusion criteria, only studies on the association between HD and AZ were included. Nausea, vomiting, diarrhea, abdominal pain and increased transaminases were related. The symptoms of vomiting and nausea were evaluated through a network meta-analysis, while the symptom of abdominal pain was evaluated through a meta-analysis. No significant associations with these symptoms were observed for HD, AZ, or their combination, compared to control. Low heterogeneity and absence of inconsistency in indirect and direct comparisons were noted. Limitations included small sample sizes, varied drug dosages, and potential publication bias during the pandemic peak. This review unveils that there are no associations between gastrointestinal adverse effects and the combined treatment of HD with AZ in the management of COVID-19, as compared to either the use of a control group or the administration of the drugs individually, on the other hand, highlighting the very low or low certainty of evidence for the evaluated outcomes. To accurately conclude the absence of side effects, further high-quality randomized studies are needed.

Cardiotoxic Effects Produced by Omeprazole and Methylene Blue in an Animal Model of Cardiac Ischemia and Reperfusion and Potential Implications for the Pharmacological Strategy for Vasoplegic Syndrome.

Defined as systemic hypotension caused by intense vasodilation due to the loss of systemic vascular resistance, vasoplegic syndrome (VS) is associated with elevated morbidity and mortality in humans. Although vasopressors such as norepinephrine and vasopressin are the first-choice drugs for VS treatment, several other drugs such as methylene blue (MB) can be used as adjuvant therapy including rescue therapy. To develop new pharmacological strategies to reduce the risk of VS, we investigated the effects of treatments with MB (2 mg/kg/IV), omeprazole (OME, 10 mg/kg/IV), and their combination in an animal model of cardiac ischemia-reperfusion (CIR). The ventricular arrhythmia (VA), atrioventricular block (AVB), and lethality (LET) incidence rates caused by CIR (evaluated via ECG) and serum levels of the cardiac lesion biomarkers creatine kinase-MB (CK-MB) and troponin I (TnI) in adult rats pretreated with saline solution 0.9% and submitted to CIR (SS + CIR group) were compared to those pretreated with MB (MB + CIR group), OME (OME + CIR group), or the MB + OME combination (MB + OME + CIR group). The AVB and LET incidence rates in the MB + CIR (100%), OME + CIR (100%), and MB + OME + CIR (100%) groups were significantly higher compared to the SS + CIR group (60%). The serum level of CK-MB in these groups were also significantly higher compared to the SS + CIR group, demonstrating that the treatments before CIR with MB, OME, and MB + OME produced similar effects in relation to cardiac function and the occurrence of lesions. These results demonstrate that the treatment of animals subjected to the CIR protocol with OME produced the same effects promoted by the treatment with MB, which may suggest the possibility of using OME alone or in combination with MB in medical clinics in treatment of VS.

Exploring the clinical relevance of "Angico Gum": an effective biopolymer for topical protection of oesophageal mucosa in gastroesophageal reflux disease patients.

OBJECTIVES: Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. METHODS: Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. KEY FINDINGS: Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. CONCLUSION: AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

Protective effect of alpha-ketoglutarate against water-immersion restraint stress-induced gastric mucosal damage in mice.

Gastric lesions have several aetiologies, among which stress is the most prominent. Therefore, identification of new therapies to prevent stress is of considerable importance. Alpha-ketoglutarate (α-kg) several beneficial effects and has shown promise in combating oxidative stress, inflammation, and premature aging. Thus, this study aimed to evaluate the protective effect of α-kg in a gastric damage model by water-immersion restraint stress (WIRS). Pretreatment with α-kg decreased stress-related histopathological scores of tissue oedema, cell loss, and inflammatory infiltration. The α-kg restored the percentage of type III collagen fibres. Mucin levels were preserved as well as the structure and area of the myenteric plexus ganglia were preserved after pretreatment with α-kg. Myeloperoxidase (MPO) levels and the expression of pro-inflammatory cytokines (TNF-α and IL-1ß) were also reduced following α-kg pretreatment. Decreased levels of glutathione (GSH) in the stress group were restored by α-kg. The omeprazole group was used as standard drug e also demonstrated improve on some parameters after the exposition to WIRS as inflammatory indexes, GSH and mucin. Through this, was possible to observe that α-kg can protect the gastric mucosa exposed to WIRS, preserve tissue architecture, reduce direct damage to the mucosa and inflammatory factors, stimulate the production of type III collagen and mucin, preserve the myenteric plexus ganglia, and maintain antioxidant potential. Due to, we indicate that α-kg has protective activity of the gastric mucosa, demonstrating its ability to prevent damage associated with gastric lesions caused by stress.

Pharmacological Modulation of the Ca2+/cAMP/Adenosine Signaling in Cardiac Cells as a New Cardioprotective Strategy to Reduce Severe Arrhythmias in Myocardial Infarction.

Acute myocardial infarction (AMI) is the main cause of morbidity and mortality worldwide and is characterized by severe and fatal arrhythmias induced by cardiac ischemia/reperfusion (CIR). However, the molecular mechanisms involved in these arrhythmias are still little understood. To investigate the cardioprotective role of the cardiac Ca2+/cAMP/adenosine signaling pathway in AMI, L-type Ca2+ channels (LTCC) were blocked with either nifedipine (NIF) or verapamil (VER), with or without A1-adenosine (ADO), receptors (A1R), antagonist (DPCPX), or cAMP efflux blocker probenecid (PROB), and the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by CIR in rats was evaluated. VA, AVB and LET incidences were evaluated by ECG analysis and compared between control (CIR group) and intravenously treated 5 min before CIR with NIF 1, 10, and 30 mg/kg and VER 1 mg/kg in the presence or absence of PROB 100 mg/kg or DPCPX 100 µg/kg. The serum levels of cardiac injury biomarkers total creatine kinase (CK) and CK-MB were quantified. Both NIF and VER treatment were able to attenuate cardiac arrhythmias caused by CIR; however, these antiarrhythmic effects were abolished by pretreatment with PROB and DPCPX. The total serum CK and CK-MB were similar in all groups. These results indicate that the pharmacological modulation of Ca2+/cAMP/ADO in cardiac cells by means of attenuation of Ca2+ influx via LTCC and the activation of A1R by endogenous ADO could be a promising therapeutic strategy to reduce the incidence of severe and fatal arrhythmias caused by AMI in humans.

Crucial role of carbon monoxide as a regulator of diarrhea caused by cholera toxin: Evidence of direct interaction with toxin.

The present study evaluated the role of heme oxygenase 1 (HO-1)/carbon monoxide (CO) pathway in the cholera toxin-induced diarrhea and its possible action mechanism. The pharmacological modulation with CORM-2 (a CO donor) or Hemin (a HO-1 inducer) decreased the intestinal fluid secretion and Cl- efflux, altered by cholera toxin. In contrast, ZnPP (a HO-1 inhibitor) reversed the antisecretory effect of Hemin and potentiated cholera toxin-induced intestinal secretion. Moreover, CORM-2 also prevented the alteration of intestinal epithelial architecture and local vascular permeability promoted by cholera toxin. The intestinal absorption was not altered by any of the pharmacological modulators. Cholera toxin inoculation also increased HO-1 immunoreactivity and bilirubin levels, a possible protective physiological response. Finally, using fluorometric technique, ELISA assay and molecular docking simulations, we show evidence that CO directly interacts with cholera toxin, forming a complex that affects its binding to GM1 receptor, which help explain the antisecretory effect. Thus, CO is an essential molecule for protection against choleric diarrhea and suggests its use as a possible therapeutic tool.

Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction.

BACKGROUND: Although several studies suggest that heparins prevent arrhythmias caused by acute myocardial infarction (AMI), the molecular mechanisms involved remain unclear. To investigate the involvement of pharmacological modulation of adenosine (ADO) signaling in cardiac cells by a low-molecular weight heparin (enoxaparin; ENOX) used in AMI therapy, the effects of ENOX on the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by cardiac ischemia and reperfusion (CIR) were evaluated, with or without ADO signaling blockers. METHODS: To induce CIR, adult male Wistar rats were anesthetized and subjected to CIR. Electrocardiogram (ECG) analysis was used to evaluate CIR-induced VA, AVB, and LET incidence, after treatment with ENOX. ENOX effects were evaluated in the absence or presence of an ADO A1-receptor antagonist (DPCPX) and/or an inhibitor of ABC transporter-mediated cAMP efflux (probenecid, PROB). RESULTS: VA incidence was similar between ENOX-treated (66%) and control rats (83%), but AVB (from 83% to 33%) and LET (from 75% to 25%) incidences were significantly lower in rats treated with ENOX. These cardioprotective effects were blocked by either PROB or DPCPX. CONCLUSION: These results indicate that ENOX was effective in preventing severe and lethal arrhythmias induced by CIR due to pharmacological modulation of ADO signaling in cardiac cells, suggesting that this cardioprotective strategy could be promising in AMI therapy.

Lemon gum: Non-toxic arabinogalactan isolated from Citrus × latifolia with antiproliferative property against human prostate adenocarcinoma cells.

Lemon gum (LG) obtained from Citrus × latifolia in Brazil was isolated and characterized. In addition, gum biocompatibility was evaluated in vitro and in vivo by Galleria mellonella and mice model. The cytotoxicity against tumor cells was also evaluated. The ratio of arabinose:galactose: rhamnose:4-OMe-glucuronic acid was 1:0.65:0.06:0.15. Small traces of protein were detected, emphasizing the isolate purity. Molar mass was 8.08 × 105 g/mol, with three different degradation events. LG showed antiproliferative activity against human prostate adenocarcinoma cancer cells, with percentage superior to 50 %. In vivo toxicity models demonstrated that LG is biocompatible polymer, with little difference in the parameters compared to control group. These results demonstrate advance in the study of LG composition and toxicity, indicating a potential for several biomedical and biotechnological future applications.

Laryngeal and Esophageal Mucosal Protection Using the Angico Gum Biopolymer in a Mouse Model of Reflux.

OBJECTIVE: This study aimed to evaluate the in vivo protective effect of the angico gum biopolymer in reducing the inflammatory response and preserving the integrity of the laryngeal and esophageal mucosa. STUDY DESIGN: Animal study. METHODS: A murine surgical model of gastroesophageal reflux disease was accomplished and subsequently treated with angico gum or omeprazole. On days 3 and 7 post surgery, samples of the larynx and esophagus, respectively, were collected to measure the level of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and mucosal permeability to fluorescein). RESULTS: Angico gum and omeprazole decreased laryngeal inflammation (wet weight and myeloperoxidase activity) and dramatically improved the integrity of the laryngeal mucosa. It also reduced inflammation (decreased wet weight and myeloperoxidase activity) of the esophagus and preserved the barrier function (inferred by assessing the integrity of the mucosa). CONCLUSION: This study demonstrates the protective effect of angico gum in an experimental gastroesophageal reflux disease model. Angico gum attenuates inflammation and impairment of the mucosal barrier function not only in the larynx but also in the esophagus. LEVEL OF EVIDENCE: NA Laryngoscope, 133:162-168, 2023.

Photobiomodulation exerts anti-inflammatory effects on the vascular and cellular phases of experimental inflammatory models.

Photobiomodulation therapy (PBMT) is a non-thermal therapeutic procedure widely used in clinical practice. It is considered an effective modality of treatment for the control of various inflammatory conditions with fewer adverse effects as compared to conventional therapy. However, despite the clinical effects, the mechanisms of action and dosimetric parameters of PBMT are not fully understood. This study was performed to describe the effects of two different doses of PBMT on experimental models of inflammation. Male Swiss mice were administered with 0.9% of saline or phlogistic agents (carrageenan, dextran, serotonin, histamine, or bradykinin) by intra-plantar injection and were treated with PBMT at a dose of 1 or 5 J/cm2; right after, the variation of the paw volume was made, and histopathological analysis and myeloperoxidase assay of the carrageenan-induced edematous paw tissues were performed. The action of PBMT on carrageenan-induced vascular permeability was further evaluated. Our results showed that PBMT (1 J/cm2) led to an improvement in paw edema induced by the phlogistic agents and further reduced the histological scores. Inhibition of neutrophil migration was observed following the administration of 1 and 5 J/cm2 of PBMT. However, only 1 J/cm2 of PBMT showed beneficial effects on carrageenan-induced edema. Laser at a dose of 1 J/cm2 showed cellular and vascular effects since it was able to reverse all the inflammatory parameters, and laser at a dose of 5 J/cm2 probably has only cellular effects in the presence of acute inflammation.

Modulatory Role of Carbon Monoxide on the Inflammatory Response and Oxidative Stress Linked to Gastrointestinal Disorders.

Significance: Carbon monoxide (CO) is an endogenous gaseous mediator that plays an important role in maintaining gastrointestinal (GI) tract homeostasis, acting in mucosal defense, and providing negative modulation of pathophysiological markers of clinical conditions. Recent Advances: Preclinical studies using animal models and/or cell culture show that CO can modulate the inflammatory response and oxidative stress in GI mucosal injuries and pathological conditions, reducing proinflammatory cytokines and reactive oxygen species, while increasing antioxidant defense mechanisms. Critical Issues: CO has potent anti-inflammatory and antioxidant effects. The defense mechanisms of the GI tract are subject to aggression by different chemical agents (e.g., drugs and ethanol) as well as complex and multifactorial diseases, with inflammation and oxidative stress as strong triggers for the deleterious effects. Thus, it is possible that CO acts on a variety of molecules involved in the inflammatory and oxidative signaling cascades, as well as reinforcing several defense mechanisms that maintain GI homeostasis. Future Directions: CO-based therapies are promising tools for the treatment of GI disorders, such as gastric and intestinal injuries, inflammatory bowel disease, and pancreatitis. Therefore, it is necessary to develop safe and selective CO-releasing agents and/or donor drugs to facilitate effective treatments and methods for analysis of CO levels that are simple and inexpensive. Antioxid. Redox Signal. 37, 98-114.

Moderate Physical Exercise Activates ATR2 Receptors, Improving Inflammation and Oxidative Stress in the Duodenum of 2K1C Hypertensive Rats.

Background: In addition to the cardiovascular and renal systems, the gastrointestinal tract also contains angiotensin ATR1a, ATR1b, and ATR2. We previously observed that the 2Kidney-1Clip hypertension model elicits physical exercise and gastrointestinal dysmotility, which is prevented by renin-angiotensin system blockers. Here, we investigate the effect of physical exercise on inflammation, stress biomarkers, and angiotensin II receptors in the duodenum of 2K1C rats. Methods: Arterial hypertension was induced by the 2K1C surgical model. The rats were allocated in Sham, 2K1C, or 2K1C+Exercise groups. One week after surgery, they were submitted to a physical exercise protocol (running 5x/week, 60min/day). Next, we assessed their intestinal contractility, cytokine levels (TNF-α, IL-1ß, and IL-6), oxidative stress levels (MPO, GSH, MDA, and SOD), and the gene expression of angiotensin receptors (ATR1A, ATR1B, and ATR2). Results: In comparison with the Sham group, the 2K1C arterial hypertension decreased (p<0.05) the intestinal contractility. In comparison with 2K1C, the 2K1C+Exercise group exhibited lower (p<0.05) MPO activity (22.04±5.90 vs. 78.95±18.09 UMPO/mg tissue) and higher (p<0.05) GSH concentrations in intestinal tissues (67.63±7.85 vs. 31.85±5.90mg NPSH/mg tissue). The 2K1C+Exercise group showed lower (p<0.05) cytokine levels in the intestine than 2K1C rats. In comparison with the Sham group, the 2K1C+Exercise rats showed higher (p<0.05) gene expression of ATR2 in the duodenum. Conclusion: 2K-1C hypertension elicits an oxidative stress and inflammation process in the duodenum. Physical exercise modulates the expression twice as much of ATR2 receptors, suggesting possible anti-inflammatory and antioxidant effects induced by exercise.

Anti-inflammatory effect of L-cysteine (a semi-essential amino acid) on 5-FU-induced oral mucositis in hamsters.

Oral mucositis is an inflammation of the oral mucosa mainly resulting from the cytotoxic effect of 5-fluorouracil (5-FU). The literature shows anti-inflammatory action of L-cysteine (L-cys) involving hydrogen sulfide (H2S). In view of these properties, we investigate the effect of L-cys in oral mucositis induced by 5-FU in hamsters. The animals were divided into the following groups: saline 0.9%, mechanical trauma, 5-FU 60-40 mg/kg, L-cys 10/40 mg and NaHS 27 µg/kg. 5-FU was administered on days 1st to 2nd; 4th day excoriations were made on the mucosa; 5th-6th received L-cys and NaHS. For data analysis, histological analyses, mast cell count, inflammatory and antioxidants markers, and immunohistochemistry (cyclooxygenase-2(COX-2)/inducible nitric oxide synthase (iNOs)/H2S) were performed. Results showed that L-cys decreased levels of inflammatory markers, mast cells, levels of COX-2, iNOS and increased levels of antioxidants markers and H2S when compared to the group 5-FU (p < 0.005). It is suggested that L-cys increases the H2S production with anti-inflammatory action in the 5-FU lesion.

Alendronate sodium-polymeric nanoparticles display low toxicity in gastric mucosal of rats and Ofcol II cells.

The use of bisphosphonates constitutes the gold-standard therapy for the control and treatment of bone diseases. However, its long-term use may lead to gastric problems, which limits the treatment. Thus, this study aimed to formulate a nanostructured system with biodegradable polymers for the controlled release of alendronate sodium. The nanoparticles were characterized, and its gastric toxicity was investigated in rats. The synthesis process proved to be effective for encapsulating alendronate sodium, exhibiting nanoparticles with an average size of 51.02 nm and 98.5% of alendronate sodium incorporation. The release tests demonstrated a controlled release of the drug in 420 min, while the morphological analyzes showed spherical shapes and no apparent roughness. The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintaining the normal levels of malondialdehyde and myeloperoxidase. Also, the encapsulated alendronate sodium showed no toxicity in murine osteoblastic cells, even at high concentrations.

Renal alterations caused by ligature-induced periodontitis persist after ligature removal in rats.

BACKGROUND AND OBJECTIVE: Periodontitis may crosstalk with renal diseases, yet that remains unclear. We investigated whether the renal alterations caused by induced periodontitis are reversible after removal of the ligatures in experimental ligature-induced periodontitis. MATERIAL AND METHODS: Twenty-four female rats were divided into three groups: control (without periodontitis), periodontitis (20 days of ligature-induced periodontitis), and P20-20 (20 days of ligature-induced periodontitis and 20 days after ligature removal). The following periodontal parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, and alveolar bone height. For renal tissues, histopathology, malonaldehyde (MDA) levels, glutathione (GSH) content, and renal weight were evaluated. In the blood, creatinine, uric acid, albumin, total cholesterol, total protein, and glucose levels were assessed. Total protein and creatinine levels in urine were also investigated. RESULTS: Rat renal tissues did not demonstrate reversal of periodontitis-related changes in the P20-20 group in terms of MDA, GSH, and histopathological evaluations when compared to the periodontitis group. Accordingly, only total cholesterol levels were reversible in the P20-20. CONCLUSION: Renal alterations caused by ligature-induced periodontitis persisted even after removal of ligatures in rats.

L-Glutamine and Physical Exercise Prevent Intestinal Inflammation and Oxidative Stress Without Improving Gastric Dysmotility in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1ß, IL-6, and (TNF-α) levels. The UC significantly increased (p < 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p < 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p < 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p < 0.05) the increase of microscopic scores and oxidative stress (p < 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p < 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1ß, IL-6, and TNF-α compared with the UC group (p < 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.

Premises among SARS-CoV-2, dysbiosis and diarrhea: Walking through the ACE2/mTOR/autophagy route.

Recently, a new coronavirus (SARS-CoV-2) was discovered in China. Due to its high level of contagion, it has already reached most countries, quickly becoming a pandemic. Although the most common symptoms are related to breathing problems, SARS-CoV-2 infections also affect the gastrointestinal tract culminating in inflammation and diarrhea. However, the mechanisms related to these enteric manifestations are still not well understood. Evidence shows that the SARS-CoV-2 binds to the angiotensin-converting enzyme receptor 2 (ACE2) in host cells as a viral invasion mechanism and can infect the lungs and the gut. Other viruses have already been linked to intestinal symptoms through binding to ACE2. In turn, this medical hypothesis article conjectures that the ACE2 downregulation caused by the SARS-CoV-2 internalization could lead to decreased activation of the mechanistic target of mTOR with increased autophagy and lead to intestinal dysbiosis, resulting in diarrhea. Besides that, dysbiosis can directly affect the respiratory system through the lungs. Although there are clues to other viruses that modulate the ACE2/gut/lungs axis, including the participation of autophagy and dysbiosis in the development of gastrointestinal symptoms, there is still no evidence of the ACE2/mTOR/autophagy pathway in SARS-CoV-2 infections. Thus, we propose that the new coronavirus causes a change in the intestinal microbiota, which culminates in a diarrheal process through the ACE2/mTOR/autophagy pathway into enterocytes. Our assumption is supported by premises that unregulated intestinal microbiota increases the susceptibility to other diseases and extra-intestinal manifestations, which can even cause remote damage in lungs. These putative connections lead us to suggest and encourage future studies aiming at assessing the aforementioned hypothesis and regulating dysbiosis caused by SARS-CoV-2 infection, in order to confirm the decrease in lung injuries and the improvement in the prognosis of the disease.

Anti-Inflammatory, Antinociceptive, and Antioxidant Properties of Anacardic Acid in Experimental Models.

Anacardic acid (AA), a compound extracted from cashew nut liquid, exhibits numerous pharmacological activities. The aim of the current investigation was to assess the anti-inflammatory, antinociceptive, and antioxidant activities of AA in mouse models. For this, Swiss albino mice were pretreated with AA (10, 25, 50 mg/kg, intraperitoneally, ip) 30 min prior to the administration of carrageenan, as well as 25 mg/kg of prostaglandin E2, dextran, histamine, and compound 48/80. The antinociceptive activity was evaluated by formalin, abdominal, and hot plate tests, using antagonist of opioid receptors (naloxene, 3 mg/kg, ip) to identify antinociceptive mechanisms. Results from this study revealed that AA at 25 mg/kg inhibits carrageenan-induced edema. In addition, AA at 25 mg/kg reduced edema and leukocyte and neutrophilic migration to the intraperitoneal cavity, diminished myeloperoxidase activity and malondialdehyde concentration, and increased the levels of reduced glutathione. In nociceptive tests, it also decreased licking, abdominal writhing, and latency to thermal stimulation, possibly via interaction with opioid receptors. Taken together, these results indicate that AA exhibits anti-inflammatory and antinociceptive actions and also reduces oxidative stress in acute experimental models, suggesting AA as a promising compound in the pharmaceutical arena.

Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.

Sulfated polysaccharide from Gracilaria caudata reduces hypernociception and inflammatory response during arthritis in rodents.

Polysaccharide from marine alga Gracilaria caudata has potential health benefits, such as anti-inflammatory, gastroprotective and antidiarrheal effects. Here, we investigated the effect of a sulfated polysaccharide from G. caudata (SP-GC) on hypernociception and inflammatory response in arthritis models. The animals received SP-GC (3, 10 or 30 mg/kg) 1 h before tibio-tarsal injection of zymosan. Hypernociception, histopathology, edema, vascular permeability, myeloperoxidase (MPO) activity, cell influx, interleukin (IL)-1ß and nitric oxide (NO) levels were evaluated in acute phase. In another protocol, animals received SP-GC (30 mg/kg) 2 h post-complete Freund's adjuvant (CFA). Hypernociception, edema and arthritis index were determined in acute, sub-chronic and chronic phases. Rota-rod test measured the motor performance. SP-GC significantly reduced, in a dose-dependent manner, the zymosan-induced hypernociception with maximal effect at 30 mg/kg. The microscopic inflammation, joint edema, MPO activity, cell influx, IL-1ß and NO levels were also reduced by SP-GC. In the CFA-induced arthritis, SP-GC inhibits the hypernociception, edema and arthritic index in acute, sub-chronic and chronic phases. SP-GC did not alter the motor performance of animals. In conclusion, SP-GC exerts protective effect in models of arthritis due to the modulation of cell influx, IL-1ß and NO levels, culminating in the reduction of hypernociception and edema.