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Öğe Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS(BMC, 2022) Terzi, Funda; Demirci, Beste; Çınar, İrfan; Alhilal, Mohammad; Erol, Huseyin SerkanAbstract Background: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of infammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the efects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. Methods: Adult male rats were divided into fve groups: the CN (healthy rats, n=6), OA (oleic acid administration, n=6), OA+TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n=6), OA+TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n=6), and OA+DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n=6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. Results: Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P<0.05). The MDA level in lung tissues was statistically lower in the OA+TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P<0.05). Histopathological fndings such as thickening of the alveoli, hyperemia, and peribronchial cell infltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA+TCZ-2, and OA+TCZ-4 groups. Conclusions: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were efective in preventing cytokine storms by downregulating the expression of proinfammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective efects against cell damage.Öğe Estradiol and ascorbic acid alleviate malathion-induced lung damage in albino Wistar rats: A histopathological study(2024) Alhilal, Mohammad; Salem, Mahmoud Elsayed MohamedAim: To assess the modulatory role ofestradiol and ascorbic acidin malathion-induced pulmonary toxicity in albinoWistarrats. Methods: A total of twenty albino Wistar rats were randomly divided into four groups; the control group (group 1) was given corn oil alone, the test group (group 2) received a daily dose of malathion 20 mg/kg in corn oil, treatment group A (group 3) was administered a daily dose of malathion 20 mg/kg in corn oil plus estradiol 40 μg/100 g (gram), and treatment group B (group 4) received a daily dose of malathion 20 mg/kg in corn oil plus ascorbic acid 100 mg/kg. Experimental rats were administered once daily for four weeks. The lungs were examined histopathologically using two staining methods (Hematoxylin and Eosin, Masson Trichrome).Results: There were significant reductions in degeneration, interstitial pneumonia and interstitial fibrosis for group 3 (treatment group A) compared to group 2 (test group) (p<0.05). These reductions were more statisticallysignificant for group 4 (treatment group B) compared to group 2 (test group) (p<0.01).Therefore, the damage was less pronounced and injury severity was moderate in group 3 treated with estradiol. Group 4, with ascorbic acid, showed the mostimprovement with significant tissue repair under microscopic examination andmild injury compared to group 3.Conclusions: The results of our present study suggest that both estradiol and ascorbic acid have clear protective effects against malathion-induced lung injury. However, ascorbic acid exhibited more pronounced protective effects compared to estradiol. With more comprehensive studies, the positive effects of ascorbic acid and estradiol can be used to prevent lung damage in individuals exposed to malathion.Öğe Isocarpine as A New Peperidine Alkaloid from Adenocarpus Complicatus with Anticandidal Activity(Ingenta Connect, 2022) Alhilal, Mohammad; Alhilal, Suzan; Gomha, SobhiBackground: Adenocarpus complicatus L. is one of Adenocarpus genus, which has about 50 species, from Fabaceae (Papilionaceae) family. This plant is found in the Mediterranean basin as a southern west part of Europe and North Afric forestes. Objective: Isolation of Isocarpine From Adenocarpus Complicatus as Anticandidal Agent. Methods: A new piperidine alkaloid Isocarpine was isolated from the aerial parts of Adenocarpus complicatus L., which is gross in Syria. The structure of the new compound was determined by UV, IR, EI-Ms, 1H-NMR, 13C-NMR, DEPT-135, DQF-COSY and HMQC. Results: The anticandidal activity of isocarpine was screened against 38 Candida strains and showed remarkable inhibitory effect compared with fluconazole as an antifungal reference drug. Conclusion: Isocarpine is antifungal agent.Öğe Novel thiadiazole-thiazole hybrids: synthesis, molecular docking, and cytotoxicity evaluation against liver cancer cell lines(Taylor & Francis Online, 2022) Aljohani, Ghadah F.; Abolibda, Tariq Z.; Alhilal, Mohammad; Al-Humaidi, Jehan Y.; Alhilal, Suzan; Ahmed, Hoda A.; Gomha, Sobhi M.One of the worst diseases, cancer claims millions of lives each year throughout the world, necessitating the creation of novel treatments. In this study, we designed a novel series of 1,3,4-thiadiazoles through the reaction of 2-(4-methyl-2-(2-(1-phenylethylidene)hydrazineyl)thiazole-5-carbonyl)-N-phenylhydrazine-1-carbothioamide (3) with the proper hydrazonoyl halides. Using the MTT assay, the newly synthesized thiadiazoles' growth-inhibitory potential against the liver cancer cell line HepG2-1 was assessed. In comparison to the standard drug doxorubicin (IC50 = 0.72 ± 0.52 µM), the results showed that two compounds, 16b and 21 (IC50 = 0.69 ± 0.41 and 1.82 ± 0.94 µM, respectively) had promising anticancer activity. The structural activity relationship (SAR) was investigated. In addition, molecular docking analysis onto quinone oxidoreductase2 (NQO2) receptor (PDB: 4ZVM) was investigated against the potent compounds to examine the reliability of the in vitro results. The newly prepared thiadiazole-thiazole hybrids are therefore regarded as potent anticancer drugs.Öğe Osajin from Maclura pomifera alleviates sepsis-induced liver injury in rats: biochemical, histopathological and immunohistochemical estimation(Taylor & Francis Online, 2023) Alhilal, Mohammad; Huseyin Serkan Erol, Serkan Yildirim, Ahmet Cakir, Murat Koc, Demet Celebi, Mesut Bunyami HaliciThis paper aimed to examine the impact of flavonoid osajin (OSJ) on liver damage induced by sepsis. A total of 30 male rats were divided into 5 groups (Sham, sepsis, OSJ 150, OSJ 300 and reference). During sepsis, elevated lipid peroxidation (LPO) level and catalase activity (CAT) and decreased glutathione (GSH) level and superoxide dismutase (SOD) activity were observed in hepatic tissues of sepsis group in comparison with Sham group. A strong interleukin-33 and caspase-3 expressions were detected in hepatic tissues of sepsis group. On the contrary, OSJ administration to OSJ 300 group showed a significant decrease (P < 0.001) in LPO level (176±2.926) and significant increase (P < 0.001) in GSH level (10.586±0.083) and SOD activity (29.152±0.094) in comparison with sepsis group (185.777±1.735, 8.246±0.124, 24.307±0.379 respectively). In addition, the consumption of OSJ reduced expressions of interleukin-33 and caspase-3 and improved histopathological integrity. In conclusions, OSJ has hepatoprotective effect against sepsis-induced liver injury.Öğe Synthesis and biological evaluation of new aza-acyclic nucleosides and their hydrogen complexes from indole(SpringerLink, 2022) Alhilal, Suzan; Alhilal, Mohammad; Gomha, Sobhi M.; Ouf, Salama A.Three novel aza-acyclic nucleosides and two hydrogen complexes were isolated by flash chromatography after being produced in a reaction between indole and dibenzosulfonyl diethylamine (which had previously been prepared) in the presence of sodium and absolute ethanol as a basic catalyst. Structures of new compounds and complexes were determined by 1D-NMR: 1H NMR, 13C NMR, DEPT-135, 2D-NMR: COSY, HMQC, HSQC, HMBC, IR, and MS spectroscopy. The synthesized compounds were evaluated against a wide range of microorganisms, including Gram-positive and Gram-negative bacteria as well as fungal strains. These compounds showed good biological activity.Öğe Synthesis of Novel Acyclic Nucleoside Analogue Starting From 6-Aminouracil as Potent Antimicrobial Agent(Polycyclic Aromatic Compounds, 2021) Alhilal, Mohammad; Sulaiman, Yaser A. M.; Alhilal, Suzan; Gomha, Sobhi M.; Ouf, Salama A.6-Aminouracil and 2-bromoethyl amine were prepared, as starting materials to be introduced as an alkylating reagent with sodium carbonate as a catalyst. Acyclic nucleoside was prepared for the first time, the expected structure of the final new compound 3 was determined based on IR, NMR, and mass spectroscopy, with safe and mild reaction conditions. The synthesized acyclic nucleoside has a potent and efficient antimicrobial activity compared to reference drugs particularly as an antibacterial agent, and can be used as an alternative to the commonly used antibiotics after performing the necessary biological research for its validation.