Saeed Kolahian

Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells

Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present study, we aimed to determine the effects of muscarinic receptor stimulation on cytokine production by human airway smooth muscle cells (primary and immortalised cell lines). The muscarinic receptor agonists carbachol and methacholine both induced modest effects on basal interleukin (IL)-8 and -6 secretion, whereas the secretion of RANTES, eotaxin, vascular endothelial growth factor-A and monocyte chemoattractant protein-1 was not affected. Secretion of IL-8 and -6 was only observed in immortalised airway smooth muscle cells that express muscarinic M3 receptors. In these cells, methacholine also significantly augmented IL-8 secretion in combination with cigarette smoke extract in a synergistic manner, whereas synergistic effects on IL-6 secretion were not significant. Muscarinic M3 receptors were the primary subtype involved in augmenting cigarette smoke extract-induced IL-8 secretion, as only tiotropium bromide and muscarinic M3 receptor subtype selective antagonists abrogated the effects of methacholine. Collectively, these results indicate that muscarinic M3 receptor stimulation augments cigarette smoke extract-induced cytokine production by airway smooth muscle. This interaction could be of importance in patients with chronic obstructive pulmonary disease.

Effects of the Flavanone combination Hesperetin‐Naringenin, and Orange and Grapefruit Juices, on Airway inflammation and Remodeling in a murine asthma model

We investigated whether flavanones, hesperetin–naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non‐asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra‐alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM‐induced asthma. Copyright

Effects of metoclopramide on emesis in cats sedated with xylazine hydrochloride.

The prophylactic anti-emetic effect of five dosages of metoclopramide (0.2, 0.4, 0.6, 0.8 and 1 mg/kg, IM) was evaluated against saline solution, both injected 1 h before administration of xylazine in cats. Saline was administered to cats (day 0) followed by sequentially increasing dosages of metoclopramide at 1-week intervals. After xylazine injection, all cats were carefully observed to record the frequency of emesis and the time until onset of the first emetic episode. The onset of sedation in these cats was also studied. Prior treatment with each dosage of metoclopramide significantly reduced the frequency of emetic episodes (P<0.05). Metoclopramide administration prior to xylazine injection did not alter the time until onset of the first emetic episode at any of mentioned dosages, but significantly reduced the time until onset of sedation only at the dose of 1 mg/kg. Metoclopramide may be used as a prophylactic anti-emetic in cats sedated with xylazine hydrochloride.

Supplementation of Diabetic Rats with Leucine, Zinc, and Chromium: Effects on Function and Histological Structure of Testes

The objective was to study whether leucine, zinc, and chromium supplementations influence function and histological structure of testes in a rat model of type 2 diabetes. Seventy seven adult male rats were categorized into 11 groups of 7 animals each: (1) nondiabetic (negative control); (2) non-treated (positive control); (3) treated with insulin; (4) treated with glibenclamide; (5) treated with leucine; (6) treated with zinc; (7) treated with chromium; (8) treated with leucine + zinc; (9) treated with leucine + chromium; (10) treated with zinc + chromium; (11) treated with leucine + zinc + chromium. In the non-treated group, hyperglycemia severely damaged testes morphology as well as the spermatogenic process. Diabetes induction decreased testicular length, height, width, volume, total number of epididymal sperm, and number of live sperm. Seminiferous tubules of diabetic rats showed a decrease in diameter of tubules and height of epithelium. Diabetes induction decreased the number of cells (spermatogonia, spermatocyte, spermatid, and Sertoli) in cross sections of seminiferous tubules. Administration of nutritional supplements to the diabetic rats improved testes morphology and reversed, although not completely, impairment of spermatogenesis. Treatment with nutritional supplements increased testicular length, height, width, and volume. All treatments increased the number of live sperm and the total number of epididymal sperm. Furthermore, nutritional supplements increased diameter of tubules, height of epithelium, and the number of cells in seminiferous tubules. These alleviating effects were more pronounced in animals treated with the leucine-zinc-chromium combination. The present results demonstrate beneficial effects of zinc, leucine, and chromium supplements to improve testes morphology and to restore spermatogenesis in type 2 diabetic rats.

Airway inflammatory events in diabetic-antigen sensitized guinea pigs.

Experimental evidence indicates that the relative lack of insulin in an organism results in an overall reduction in inflammatory reactions. This study was planned to determine the inflammatory events in antigen sensitized diabetic guinea pigs. Twenty-five male guinea pigs were categorized into five groups of five each as follows: diabetic, antigen sensitized, antigen sensitized diabetic, insulin-treated antigen sensitized diabetic and control animals. Induction of experimental diabetes and antigen sensitization was performed by injection of streptozotocin and ovalbumin, respectively. Animals were killed by exsanguination and bronchoalveolar lavage was performed. Bronchoalveolar lavage fluid cellular and protein contents were determined. Airway responsiveness to acetylcholine was assessed using isolated tracheal triple-ring. Histopathological examinations were performed on the lungs. Decreases in the airway reactivity in diabetic and antigen sensitized diabetic animals were found compared with antigen sensitized animals. Experimental diabetes also decreased antigen-induced protein leakage into the airspace as well as the accumulation of inflammatory cells (eosinophils, neutrophils, lymphocytes and macrophages) in bronchoalveolar lavage fluid of antigen sensitized animals. Insulin treatment prevented these decreases in protein content and inflammatory cells infiltration in bronchoalveolar lavage fluid observed in the antigen sensitized guinea pigs with diabetes. Histopathological results showed that coinduction of experimental diabetes significantly reduces the number of eosinophils in the lungs of antigen sensitized animals. Again, treatment with insulin increased the number of eosinophils in the antigen sensitized diabetic animals. Experimental diabetes causes were found to decrease the airway reactivity and inflammatory responsiveness induced by antigen sensitization due to a reduction in the insulin levels.

Tiotropium effects on airway inflammatory events in the cat as an animal model for acute cigarette smoke-induced lung inflammation

ABSTRACT Background: Chronic obstructive pulmonary disease is an inflammatory lung disease mainly caused by tobacco smoke inhalation. Methods: Fifteen healthy adult male cats were categorized into 3 groups: (1) control group, (2) exposed to cigarette smoke (CS), and (3) exposed to CS treated with tiotropium. Results: Increases in clinical signs and airway responsiveness in CS cats were found compared to control animals. The airway hyperresponsiveness and clinical signs were significantly attenuated by treatment with tiotropium. The CS-induced pulmonary release of interleukin-6, interleukin-8, monocyte chemotactic protein-1, and tumor necrosis factor alpha was reduced in the tiotropium group. Exposure to CS significantly increased total inflammatory cells number in bronchoalveolar lavage fluid, which was significantly attenuated by treatment with tiotropium. The number of macrophages, eosinophils and neutrophils and lymphocytes was increased after exposure to CS. Tiotropium significantly reduced the number of all these cells. Perivascular, peribronchiolar infiltration of inflammatory cells and Reid index increased in the CS group. Treatment with tiotropium significantly reduced these parameters to control level. Enhanced lipid peroxidation with concomitant reduction of antioxidants status was observed in the CS group. Tiotropium significantly reduced the serum, lung lavage, lung, and tracheal tissue lipid peroxides to near control levels. Tiotropium also decreased lung and tracheal protein leakage, and prevented the reduction of total antioxidant status in serum, lung lavage, lung and tracheal tissue of the CS group. Conclusion: Cigarette smoke increases airway responsiveness and inflammation in a cat model of CS induced lung inflammation. It can effectively be reduced by treatment with tiotropium.

The Effects of Leucine, Zinc, and Chromium Supplements on Inflammatory Events of the Respiratory System in Type 2 Diabetic Rats

Diabetes mellitus is a major cause of serious micro- and macrovascular diseases that affect nearly every system in the body, including the respiratory system. Non-enzymatic protein glycation due to hyperglycaemic stress has fundamental implications due to the large capillary network and amount of connective tissue in the lung. The current study was designed to determine whether leucine, zinc, and chromium supplementations influence the function and histological structure of the respiratory tract in a rat model of type 2 diabetes. Seventy-seven rats were divided into eleven groups, consisting of 7 animals each. One group served as negative control and insulin and glibenclamide were used as positive control drugs. Thus, eight groups received the nutritional supplements alone or in combination with each other. Nutritional supplements and glibenclamide were added to the drinking water and neutral protamine Hagedorn insulin was subcutaneously injected during the 4 weeks of treatment period. The induction of type 2 diabetes in the rats caused an infiltration of mononuclear cells and edema in the submucosa of the trachea and lung, severe fibrosis around the vessels and airways, and perivascular and peribronchial infiltration of inflammatory cells and fibrin. In the diabetic group, the total inflammation score and Reid index significantly increased. Diabetes induction significantly reduced the total antioxidant status and elevated the lipid peroxidation products in the serum, lung lavage and lung tissue of the diabetic animals. Treatment with nutritional supplements significantly decreased the histopathological changes and inflammatory indices in the diabetic animals. Supplementation of diabetic rats with leucine, zinc, and chromium, alone and in combination, significantly increased the total antioxidant status and lipid peroxidation level in the diabetic animals. The nutritional supplements improved the enzymatic antioxidant activity of catalase, glutathione peroxidase, myeloperoxidase, and superoxide dismutase in the diabetic rats. The present results demonstrate beneficial effects and amelioration of inflammation in the respiratory system of type 2 diabetic rats by leucine, zinc, and chromium supplements, probably due to their hypoglycaemic and antioxidant properties. Using safe and effective nutritional supplements, such as leucine, chromium and zinc, to replace proven conventional medical treatments may help to control diabetes and/or its complications.