Effects of Azithromycin on Behavior, Pathologic Signs, and Changes in Cytokines, Chemokines, and Neutrophil Migration in C57BL/6 Mice Exposed to Dextran Sulfate Sodium

Abstract

Here we characterized the murine dextran sulfate sodium (DSS) model of acute colitis. Specifically, we evaluated azithromycin and metronidazole treatment regimens to assess their effects on animal wellbeing, pathologic changes, barrier function, cytokine and chemokine profiles, and neutrophil migration in colon tissue. Azithromycin treatment significantly reduced the severity of colitis, as assessed through body weight change, water consumption, macroscopic lesions, and animal behaviors (activity level, climbing, and grooming), but did not alter food consumption or feeding behavior. Mucosal barrier function (evaluated by using FITC-labeled dextran) was decreased after DSS exposure; azithromycin did not significantly alter barrier function in mice with colitis, whereas metronidazole exacerbated the colitis-related deficit in barrier function. In addition, metronidazole appeared to exacerbate disease as assessed through water consumption and animal behaviors (overall activity, climbing, grooming, and drinking) but had no effect on weight loss, macroscopic lesions, or eating behavior. Pathologic changes were typical for DSS treatment. Antibiotic treatment resulted in reduced levels of proinflammatory cytokines and chemokines and decreased neutrophil adhesion and emigration in DSS-exposed mice. The results highlight the importance of clinical and behavioral assessments in addition to laboratory evaluation as tools to evaluate animal welfare and therapeutic efficacy in disease models. Data from this study suggest that azithromycin may convey some benefits in the mouse DSS colitis model through modulation of the immune response, including neutrophil migration into tissues, whereas metronidazole may exacerbate colitis.

Targeting Neutrophils to Treat Acute Respiratory Distress Syndrome in Coronavirus Disease

“…With respect to the effect of azithromycin on neutrophils, Bystrzycka et al revealed that azithromycin decreased NET release in activated neutrophils in vitro ( Bystrzycka et al, 2017 ). Anderson et al demonstrated that azithromycin inhibited neutrophil migration in dextran sulfate sodium-induced mice ( Anderson et al, 2019 ). However, Cavalcanti et al showed that hydroxychloroquine and azithromycin did not alter disease progression in patients with mild-to-moderate COVID-19 ( Cavalcanti et al, 2020 ).…”

The susceptibility of the aortic root: porcine aortic rupture testing under cardiopulmonary bypass

“…The quantity of Collagen I, III and IV are all significantly reduced in human aneurysms compared to non-aneurysmal acute ruptured porcine samples. Reassuringly there is good reproducibility of quantification between porcine and human non-aneurysmal samples as shown in earlier studies [ 4 – 13 ].…”

“…Using a physiological model, results could identify patterns in radiological, pathological, and histological changes that affect the aorta under stress. Although no studies apart from Surman et al [ 1 ] have reported on the maximal pressures obtained in the porcine aortic root and ascending aorta, many studies have showed that a porcine model is effective in the application of cardiopulmonary bypass and replicating models applicable to human subjects in cardiothoracic surgery [ 4 – 13 ].…”

“…Hyperosmolar priming solution is beneficial for CPB in swine to reduce fluid shifts, metabolic acidosis, and hemoglobinuria Nicols et al [ 11 ] To determine the effect of changing FiO2-concentration on SvO2 in a swine model on CPB 8 mixed-gender swine were placed on CPB with an experimental and control group measuring percentage change in blood flow and oxygen delivery Results suggest that decreased blood flow adjusting for increased SvO2 associated with high PaO2 did not result in significant reduction in adequacy of perfusion markers for organs studied Oizumi et al [ 1 ] Development of a swine model for anatomical thoracoscopic lung segmentectomy training 33 pigs were used over a period of 5 years to train operators on segmentectomy via a hybrid (8) or thoracoscopic (23) approach. 3 pigs were converted to thoracotomy due to hemorrhage Live swine model was considered a good choice for training surgeons on how to perform a minimally invasive lung segmentectomy in humans Thalmann et al [ 13 ] Evaluation of several hybrid approaches for pulmonary valve replacement in a swine model 13 pigs were used using 4 different thoracotomy methods for valve implantation, and 5 cases used median sternotomy Achieved implantation of 12/13 stented valves of which 41% were in the optimal position and 16% had paravalvular leakage. Lower partial sternotomy provided the best deemed approach …”

Nonantimicrobial Actions of Macrolides: Overview and Perspectives for Future Development

“…The evidence for local anti-inflammatory effects of macrolides in populations suffering from IBD is hard to find. Preclinical evidence exists suggesting potential use of macrolides as immunomodulators in gut inflammation (Anderson et al, 2019). Intriguingly, it has been shown with the murine dextran sulfate sodium colitis model that single early-life treatment with antibiotics, including the macrolide tylosin, can disturb the gut microbial environment sufficiently to exacerbate subsequent IBD later in life (Ozkul et al, 2020).…”