The impact of Sambucus nigra L. extract on inflammation, oxidative stress and tissue remodeling in a rat model of lipopolysaccharide-induced subacute rhinosinusitis.

Rhinosinusitis is a common disorder related to inflammation of paranasal sinuses and nasal cavity mucosa. Herbal medicines could be an option in the treatment of rhinosinusitis due to their anti-inflammatory and anti-oxidative properties. The study aims to investigate the effect of intranasal Sambucus nigra L. subsp. nigra (SN) extract against inflammation, oxidative stress, and tissue remodeling in nasal and sinus mucosa, but also in serum, lungs, and brain, in Wistar rat model of subacute sinonasal inflammation induced by local administration of lipopolysaccharides (LPS), from Escherichia Coli. The cytokines (TNF-α, IL-1ß, IL-6) and oxidative stress (malondialdehyde) in nasal mucosa, blood, lungs, and brain were analyzed. In addition, a histopathological examination was performed, and NF-kB, MMP2, MMP9, TIMP1 expressions were also evaluated in nasal mucosa. Both doses of LPS increased the production of cytokines in all the investigated tissues, especially in the nasal mucosa and blood (p < 0.01 and p < 0.05), and stimulated their secretion in the lungs, and partially in the brain. Malondialdehyde increased in all the investigated tissues (p < 0.01 and p < 0.05). In parallel, upregulation of NF-kB and MMP2 expressions with downregulation of TIMP1, particularly at high dose of LPS, was observed. SN extract reduced the local inflammatory response, maintained low levels of IL-6, TNF-α, and IL-1ß. In lungs, SN reduced all cytokines levels while in the brain, the protective effect was noticed only on IL-6. Additionally, SN diminished lipid peroxidation and downregulated NF-kB in animals exposed to a low dose of LPS, with increased TIMP1 expression, while in animals treated with a high dose of LPS, SN increased NF-kB, MMP2, and MMP9 levels. In conclusion, SN extract diminished the inflammatory response, reduced generation of reactive oxygen species (ROS) and, influenced MMPs expressions, suggesting the benficial effect of SN extract on tissue remodeling in subacute rhinosinusitis and on systemic inflammatory response.

Biomarkers of pediatric obstructive sleep apnea syndrome and the assessment of quality of life before and after adenotonsillectomy.

The study aims to explore the inflammatory cytokines and oxidative stress in children with obstructive sleep apnea syndrome (OSAS) triggered by adenoids and/or tonsillar hypertrophy and their changes after adenotonsillectomy (AT) and to investigate the associated behavioral disorders in OSAS, before and after AT. Thirty patients with OSAS and 20 healthy children, aged 3 - 13 years were included in the study. According to apnea-hypopnea index (AHI), OSAS children were classified into 3 groups: mild (n = 19), moderate (n = 5), and severe OSAS (n = 6). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) and antioxidant enzymes activities were assessed in serum, preoperative and 6 weeks after AT. TNF-α, IL-6 and malondialdehyde levels were also estimated in adenoid and tonsils tissues. A Pediatric Sleep Questionnaire was completed by the parents before and after AT. As a result of the study, we obtained the following results: TNF-α, IL-6 and malondialdehyde evaluated preoperative increased in serum and tissues in OSAS, especially in severe disease compared to mild and moderate forms. Six weeks after AT, AHI diminished significantly in OSAS, as well as the inflammatory markers and malondialdehyde, in parallel with significant improvement of antioxidant enzymes activities. Daytime sleepiness, hyperactivity and attention deficit in OSAS, even in mild disease were present, with significant improvements of obstructive symptoms after AT. We conclude that OSAS caused by adenoids and/or tonsillar hypertrophy led to changes in the blood parameters, with significant improvement after AT. Postoperatively, a significant improvement in sleep quality and behavior in OSAS patients was also observed.

Quercetin attenuates naso-sinusal inflammation and inflammatory response in lungs and brain on an experimental model of acute rhinosinusitis in rats.

This study aimed to investigate the effect of quercetin without intranasal inflammation and oxidative stress in nasal and sinus mucosa, but also in serum, lungs and brain in a rat model of acute nasal and sinus inflammation induced by administration of lipopolysaccharides (LPS) (from Escherichia coli). Wistar rats were divided into five groups of 10 animals each. The control group received an intranasal saline solution once/day, for seven consecutive days. Rats in groups 2 and 3, received low-dose (5 µg) and high-dose (10 µg) of LPS, once/day, for seven consecutive days. Rats in groups 4 and 5, received low-dose (5 µg) and high-dose (10 µg) of LPS and after 2 h, 80 mg/kg of quercetin, once/day for seven consecutive days was administered. After the treatment period, the histopathological examination of nasal and sinus mucosa was performed and levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6)) and oxidative stress in the blood, nasal mucosa, lungs and brain were also analyzed. High dose of LPS increased TNF-α, IL-6 and IL-1ß levels in serum, nasal mucosa, and lungs homogenates while in brain, this effect was only on TNF-α levels. IL-1ß enhanced significantly in serum and mucosa, especially after administration of a high dose of LPS (P < 0.01 and P < 0.05). Histopathological and immunofluorescence analysis revealed acute inflammatory reaction in rats treated with both doses of LPS without significant changes of lipid peroxidation in the studied tissues. Quercetin administration diminished the exudate and degree of inflammation in lamina propria of nasal and sinusal areas, parallel with the decreased secretion of TNF-α (40.2% reduction after the low dose of LPS, and 35.4% reduction after the high dose of LPS) and IL-6 (21.4% reduction after the low dose of LPS and 35.8% reduction after the high dose of LPS). In lungs, quercetin reduced TNF-α (43.3%) and IL-6 levels (24.5%), and in the brain, the protective effect was noticed only on TNF-α (46.5%). The intranasal LPS administration successfully induced acute rhinosinusitis in a rat model and also generated an inflammatory response in the lungs and brain. Intranasal administration of quercetin diminished the nasal inflammation and also exerted protective effect on lungs and partially on brain inflammatory reaction.