Nebivolol possesses multifaceted actions that make it advantageous to combat the CsA-induced toxic effects on renal and endothelial functions.

To evaluate the chondroprotective effect of L-carnitine in relation to glucosamine sulfate and in an experimental model of osteoarthritis (OA). Materials and methods: Thirty-two adult male Wister albino rats weighing 150-210 g were assigned randomly into 4 groups: 8 rats in each group, group I (control group), group II (MIA induced OA group), group III (MIA induced OA + glucosamine sulfate treated group), and group IV (MIA induced OA + L-carnitine treated group). Weight, knee diameter, and knee bend score were recorded on days 0, 1, 7, 14 and 28. On day 28 all animals were sacrificed. Synovial fluid of left knee was collected, and the interleukin-1b (IL-1b), Cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase-13 (MMP-13) levels were measured by ELISA. The knee joints were removed and stained with H&E for histological evaluation. Results: The pathological abnormalities attributed to MIA induced arthritis was dramatically lowered in rats treated with glucosamine or L-carnitine. Synovial fluid levels of IL-1b, COMP and MMP-13 were increased in OA group, and significantly reduced with glucosamine or L-carnitine treated groups. Conclusion: L-Carnitine has a potential chondroprotective effect in this animal model of OA.

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Background: Boswellia serrata (family Burseraceae) has been traditionally used for the treatment of a wide variety of diseases as arthritis, inflammatory bowel diseases, and airway diseases. However, the direct bronchodilator efficacy of Boswellia serrata hasn’t been explored yet. Objective: We aimed at the present study to evaluate the direct effect of Boswellia serrata extract (BSE) on isolated rat tracheal preparations precontracted with either Acetylcholine (ACh) or potassium chloride (KCl). Methods: Tracheal rings were prepared from male Wistar rats (200-250 g). BSE (1-200 μg/ml) was added to tracheal strips precontracted with either ACh or KCl and the response was observed. We also investigated the consequences of epithelial denudation, indomethacin, and N-Nitro-L-arginine on the relaxant effect of BSE as compared to that of the β-adrenoceptor agonist isoprenaline, or the bitter taste receptor (TAS2R) agonist denatonium benzoate. Finally, the possible additive effects of BSE to isoprenaline or denatonium-induced relaxation were evaluated. Results: By using a set of serial dosing and washout experiments with tracheal rings, results showed that exposure to BSE resulted into a significant and concentration-dependent inhibitory effect on airway smooth muscle contractions precontracted with either ACh or KCl. Epithelial denudation, indomethacin, or N-Nitro-L-arginine had no significant effect on the obtained relaxation. Furthermore, BSE potentiated the relaxant effect of isoprenaline on rat trachea. Conclusion: BSE exerts a direct concentration-dependent relaxant effect on precontracted tracheal strips. These results could contribute towards validation of the traditional use of BSE in the treatment of airway diseases.

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Vascular calcification (VC) is a major risk factor for cardiovascular events. A mutual interplay between inflammation, oxidative stress, apoptosis, and autophagy is implicated in its development. Herein, we aimed to evaluate the potential protective effects of canagliflozin in a vitamin D3 plus nicotine (VDN) model of VC, and to explore potential mechanisms. VC was induced by VDN in adult male Wistar rats on day one. Then, rats were randomly assigned into three groups to receive canagliflozin (10 mg or 20 mg/kg/day) or its vehicle for 4 weeks. Age-matched normal rats served as a control group. After euthanization, aorta and kidneys were harvested for biochemical and histopathological evaluation of calcification. Aortic markers of oxidative stress, alkaline phosphatase (ALP) activity, runt-related transcription factor (Runx2) and bone morphogenic protein-2 (BMP-2) levels were determined. Additionally, the protein expression of autophagic markers, LC3 and p62, and adenosine monophosphate activated protein kinase (AMPK) were also assessed in aortic homogenates. Canagliflozin dose-dependently improved renal function, enhanced the antioxidant capacity of aortic tissues and reduced calcium deposition in rat aortas and kidneys. Both doses of canagliflozin attenuated ALP and osteogenic markers while augmented the expression of autophagic markers and AMPK. Histopathological examination of aortas and kidneys by H&E and Von Kossa stain further support the beneficial effect of canagliflozin. Canagliflozin could alleviate VDN-induced vascular calcification, in a dose dependent manner, via its antioxidant effect and modulation of autophagy. Further studies are needed to verify whether this effect is a member or a class effect.