Saleh A. Bahashwan

Oxidative airway inflammation leads to systemic and vascular oxidative stress in a murine model of allergic asthma

Oxidant-antioxidant imbalance plays an important role in repeated cycles of airway inflammation observed in asthma. It is when reactive oxygen species (ROS) overwhelm antioxidant defenses that a severe inflammatory state becomes apparent and may impact vasculature. Several studies have shown an association between airway inflammation and cardiovascular complications; however so far none has investigated the link between airway oxidative stress and systemic/vascular oxidative stress in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of vascular/systemic oxidant-antioxidant balance. Rats were sensitized intraperitoneally with ovalbumin (OVA) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with OVA. Rats were then assessed for airway and vascular inflammation, oxidative stress (ROS, lipid peroxides) and antioxidants measured as total antioxidant capacity (TAC) and thiol content. Challenge with OVA led to increased airway inflammation and oxidative stress with a concomitant increase in vascular inflammation and oxidative stress. Oxidative stress in the vasculature was significantly inhibited by antioxidant treatment, N-acetyl cysteine; whereas hydrogen peroxide (H2O2) inhalation worsened it. Therefore, our study shows that oxidative airway inflammation is associated with vascular/systemic oxidative stress which might predispose these patients to increased cardiovascular risk.

Anti-parkinsonism, hypoglycemic and anti-microbial activities of new poly fused ring heterocyclic candidates

A new series of poly fused pyrazolothienopyrimidine derivatives (2-14) were synthesized and their anti-parkinsonism, hypoglycemic and anti-microbial activities were evaluated. Some of the newly synthesized compounds exhibited better pharmacological and biological activities than the reference controls with low concentrations. The structures of newly synthesized compounds were confirmed by chemical, elemental and spectroscopic evidences. The detailed synthesis, spectroscopic data, and pharmacological activities were reported.

Changes in phospholipid composition, protein content and chemical properties of flaxseed oil during development.

The aim of the present research is to investigate the effect of harvest date on the composition of flaxseed. Samples were collected at regular intervals from 7 to 56 days after flowering (DAF) and analyzed for phospholipid composition, storage protein content and chemical properties. Phospholipid (PL) percentage of the total lipid decreased from 32.72% on the 7th DAF to 2.55% on the 56th DAF. The most phospholipids present in flaxseed were phosphatidylinositol (PI), phosphatidylethanolamine (PE) and lysophosphatidylcholine (LPC) which were highly unsaturated and rich in linolenic and linoleic acids, comprising together 60% of the total fatty acids. Chemical investigation of flaxseed oil showed overall a decrease in UV absorbance (K(232) and K(270)), acid value, free fatty acid content and an increase in peroxide value and storage protein content with development. At full maturity, flaxseed contained 29% proteins on a dry weight basis (DW %).

Pharmacological activities of some new polycyclic triazolopyrazolopyridazine derivatives

In continuation of our previous work, a novel series of polycyclic derivatives were synthesized and their anti-inflammatory, analgesic and antimicrobial activities were evaluated. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). Some of the newly compounds exhibited better biological and pharmacological activities than the reference controls with low toxicity (LD(50)). The structure of the new compounds has been established on the bases of chemical and spectroscopic evidences. The detailed synthesis, spectroscopic data, LD(50) and pharmacological activities of the synthesized compounds were reported.

Airway oxidative stress causes vascular and hepatic inflammation via upregulation of IL-17A in a murine model of allergic asthma

Oxidants are generated in asthmatic airways due to infiltration of inflammatory leukocytes and resident cells in the lung. Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide radical may leak into systemic circulation when generated in uncontrolled manner and may impact vasculature. Our previous studies have shown an association between airway inflammation and systemic inflammation; however so far none has investigated the impact of airway oxidative inflammation on hepatic oxidative stress and Th1/Th2/Th17 cytokine markers in liver/vasculature in a murine model of asthma. Therefore, this study investigated the contribution of oxidative stress encountered in asthmatic airways in modulation of systemic/hepatic Th1/Th2/Th17 cytokines balance and hepatic oxidative stress. Mice were sensitized intraperitoneally with cockroach extract (CE) in the presence of aluminum hydroxide followed by several intranasal (i.n.) challenges with CE. Mice were then assessed for systemic/hepatic inflammation through assessment of Th1/Th2/Th17 cytokines and oxidative stress (iNOS, protein nitrotyrosine, lipid peroxides and myeloperoxidase activity). Challenge with CE led to increased Th2/Th17 cytokines in blood/liver and hepatic oxidative stress. However, only Th17 related pro-inflammatory markers were upregulated by hydrogen peroxide (H2O2) inhalation in vasculature and liver, whereas antioxidant treatment, N-acetyl cysteine (NAC) downregulated them. Hepatic oxidative stress was also upregulated by H2O2 inhalation, whereas NAC attenuated it. Therefore, our study shows that airway oxidative inflammation may contribute to systemic inflammation through upregulation of Th17 immune responses in blood/liver and hepatic oxidative stress. This might predispose these patients to increased risk for the development of cardiovascular disorders.

Riboflavin attenuates lipopolysaccharide-induced lung injury in rats.

Abstract Riboflavin (vitamin B2) is an easily absorbed micronutrient with a key role in maintaining health in humans and animals. It is the central component of the cofactors flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) and is therefore required by all flavoproteins. Riboflavin also works as an antioxidant by scavenging free radicals. The present study was designed to evaluate the effects of riboflavin against acute lungs injury induced by the administration of a single intranasal dose (20 μg/rat) of lipopolysaccharides (LPS) in experimental rats. Administration of LPS resulted in marked increase in malondialdehyde (MDA) level (p < 0.01) and MPO activity (p < 0.001), whereas marked decrease in glutathione (GSH) content (p < 0.001), glutathione reductase (GR) (p < 0.001) and glutathione peroxidase (p < 0.01) activity. These changes were significantly (p < 0.001) improved by treatment with riboflavin in a dose-dependent manner (30 and 100 mg/kg, respectively). Riboflavin (100 mg/kg, p.o.) showed similar protective effects as dexamethasone (1 mg/kg, p.o.). Administration of LPS showed marked cellular changes including interstitial edema, hemorrhage, infiltration of PMNs, etc., which were reversed by riboflavin administration. Histopathological examinations showed normal morphological structures of lungs tissue in the control group. These biochemical and histopathological examination were appended with iNOS and CAT gene expression. The iNOS mRNA expression was increased significantly (p < 0.001) and levels of CAT mRNA expression was decreased significantly (p < 0.001) in the animals exposed to LPS, while treatment with riboflavin significantly (p < 0.01) improved expression of both gene. In conclusion, the present study clearly demonstrated that riboflavin caused a protective effect against LPS-induced ALI. These results suggest that riboflavin may be used to protect against toxic effect of LPS in lungs.

Androgen Receptor Antagonists and Anti-Prostate Cancer Activities of Some Newly Synthesized Substituted Fused Pyrazolo-, Triazolo- and Thiazolo-Pyrimidine Derivatives

A series of substituted pyrazole, triazole and thiazole derivatives (2–13) were synthesized from 1-(naphtho[1,2-d]thiazol-2-yl)hydrazine as starting material and evaluated as androgen receptor antagonists and anti-prostate cancer agents. The newly synthesized compounds showed potent androgen receptor antagonists and anti-prostate cancer activities with low toxicity (lethal dose 50 (LD50)) comparable to Bicalutamide as reference drug. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, and MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 values and pharmacological activities of the synthesized compounds are reported.

Synthesis and Pharmacological Activities of Some New Triazolo- and Tetrazolopyrimidine Derivatives

A new series of fused triazolo- and tetrazolopyrimidine derivatives 2–14 were synthesized and their anti-inflammatory and ulcerogenic activities were evaluated. The pharmacological screening showed that many of these obtained compounds have good anti-inflammatory activities, comparable to the reference drug. The toxicity of the compounds was also assayed via the determination of their LD50 values. The structures of newly synthesized compounds were confirmed by IR, 1H-NMR, MS spectral data and elemental analysis.

Protection against tacrolimus-induced cardiotoxicity in rats by olmesartan and aliskiren

Abstract Context: Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin–angiotensin aldosterone system. Objective: The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity. Materials and methods: Male Wistar albino rats weighing 200–250 g (10–12 weeks old) were used in this study. Animals were divided into four groups. Group 1 received normal saline, group 2 received TAC (2 mg/kg, intraperitoneally for 14 d), group 3 received OLM (2 mg/kg, p.o. for 28 d) + TAC and group 4 received ALK (50 mg/kg, p.o. for 28 d) + TAC. TAC-induced cardiotoxicity was assessed biochemically and histopathologically. Results: Treatment with OLM or ALK decreased the TAC-induced changes in biochemical markers of cardiotoxicity such as serum aspartate transaminase, creatine kinase and lactate dehydrogenase. OLM or ALK also attenuated the effects of TAC on oxidant–antioxidant parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that OLM or ALK also attenuated TAC-induced cardiotoxicity. Discussion and conclusion: These results suggest that OLM as well as ALK has protective effects against TAC-induced cardiotoxicity; implying that angiotensin receptor blocker or renin inhibitor, respectively, may counteract cardiotoxicity associated with immunosuppressant use.

Influence of harvest year in the physicochemical properties and antioxidant activity of flaxseed hull oils from Tunisia

The objective of this research was to determine the effect of five years on physico-chemical characteristics and antioxidant activity of flaxseed hull oils. Oil and protein on flaxseed hull varied between 20.15 and 22.56 and 17.45 and 19.14, respectively. The albumin fraction dominated the seed hull protein composition (44 - 47%). Flaxseed hull oils showed significantly high unsaturated to saturated fatty acid ratios (6.61 - 8.36) and calculated oxidizability (Cox) values (10.88 - 12.30). The physiochemical parameters determined included saponification value (SV) (174 -182 mg KOH/g), unsaponifiable matter (UM) (1.32 - 1.64%), peroxide value (PV) (1.70 - 2.20 mequiv/kg), Oxidation value (OV) (4.40 - 5.90) and oil stability (1.10 - 1.42 h). The highest content of total phenolic acids and total tocopherols were recorded on hull sample collected in 2008. Flavanoid content ranged from 11 to 19 mg/100 g oil. Antioxidant activity differed significantly; the greatest inhibition (61.38%) was for the hull sample collected in 2008.