The reaction of 2,3,7‐trichloroquinoxaline (1) or 2,3‐dichloro‐7‐bromoquinoxaline (2) with thiourea in DMSO gave 6,6′‐dichloro‐ or 6,6′‐dibromodiquinoxalino[2,3‐b:2′:3′‐e]1,4‐dithiien (3 or 4). However, 1 or 2 reacts with thiourea in ethanol to give (3 or 4) beside 7‐chloro‐ or 7‐bromo‐2‐imino‐2,3‐dihydrothiazolo[4,5‐b] quinoxaline (5 or 6) respectively. Interaction of 1 or 2 with acetone thiosemicarbazone gave 7‐chloro‐ or 7‐bromo‐3‐amino‐2‐imino‐2,3‐dihydro‐thiazolo[4,5‐b] quinoxaline hydrochloride (13 or 14) respectively. Cyclization of 7‐chloro‐ or 7‐bromo‐3‐amino‐2‐imino‐2,3‐dihydrothiazolo[4,5‐b]quinoxaline (15 or 16) on treatment with aromatic acid chlorides or isothiocyanates succeeded to give 19—21 or 28 and 29.
Introduction: Zingerone is a nontoxic important extract of dry ginger plant. It is reported that zingerone has an anticancer property, strong anti-inflammatory and antimicrobial properties. Aim of the Work: is to evaluate the possible protective effects of zingerone on ethanol-induced lesions on the jejunum of adult male albino rats. Materials and Methods: twenty four adult male albino rats were used, divided into 3 groups; A control group (I); consisted of 8 rats, ethanol group (II); contained 8 rats and each rat given 50% v/v alcohol at a dose of 4 g/kg.bw orally for 15 days. Ethanol zingerone group (III); consisted of 8 rats, each received zingerone at a dose of 50 mg/kg and alcohol at the same previous dose daily and orally for 15 days. At the appropriate time, the specimens were taken and prepared for light and electron microscope study. Results: Histological examination of jejunum sections of ethanol group (II) showed massive jejunal villi ulcerations with shedding of their surface epithelium, loss of the villous architecture and loss of the microvilli covering some enterocytes. Examination of ethanol zingerone group (III) showed evidence of improvement in the form of nearly normal architecture of the jejunal villi with few areas of ulcerations on the top of some villi and increased cells with mitotic activity. Conclusion: Accordingly, we can conclude that zingerone administration can remarkably ameliorate ethanol-induced enterotoxiciy and jejunal ulcerations in rats by its anti-inflammatory properties and by suppressing oxidative stress.
Introduction. Vigabatrin (VGB) is an antiepileptic drug that acts to irreversibly inhibit the γ-aminobutyric acid (GABA) transaminase enzyme, elevating GABA levels. Broad studies have established that long-term treatment and/or high doses of VGB lead to variable visual defects. However, little attention has been paid to its other side effects, especially those demonstrating cerebellar involvement. Sodium glucose-linked co-transporter 2 (SGLT2) inhibitors are antidiabetic agents with protective effects far greater than expected based on their anti-hyperglycemic effect. Method. Our study herein was designed to investigate the possible ameliorative effect of empagliflozin, the SGLT2 inhibitors, in VGB-induced cerebellar toxicity. A total of 40 male Wistar rats were allocated equally into 4 groups: Group I: control group; Group II: VGB group; Group III empagliflozin treated VGB group; and Group IV: empagliflozin treated group. All groups were subjected to the detection of cerebellar messenger RNA gene expression of silent mating type information regulation 2 homolog 1 (SIRT1) and Nucleoporin p62 (P62). Mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and beclin1 levels were assessed by the ELISA technique while malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were detected spectrophotometrically. Immuno-histochemical studies, focusing on glial fibrillary acidic protein (GFAP) and S100 were performed, and the optical color density and the mean area percentage of GFAP positive astrocytes and the number of S 100 positive cells were also counted. Results. Following empagliflozin treatment, we documented significant upregulation of both SIRT1 and P62 mRNA gene expression. Additionally, AMPK, Beclin1 levels, and SOD activity were significantly improved, while both mTOR and MDA levels were significantly reduced. Conclusions. We concluded for the first time that empagliflozin efficiently ameliorated the VGB-induced disrupted mTOR/AMPK/SIRT-1 signaling axis with subsequent improvement of the autophagy machinery and mitigation of the oxidative and inflammatory cellular environment, paving the way for an innovative therapeutic potential in managing VGB-induced neurotoxicity.
Introduction: Analgesics are the most commonly used drugs worldwide. Tramadol hydrochloride (opioid) is a synthetic centrally acting analgesic agent used for treating moderate to severe pain with less side effects than traditional opioid medications. Aim of the Work: To study the histological and morphometric changes of the cerebral cortex in adult albino rats after tramadol hydrochloride administration and the effect of its withdrawal. Materials and Methods: Twenty four adult albino rats were used regardless sex, divided into 3 groups: a control group: consisted of 8 rats and were furtherly subdivided into two equal subgroups: a subgroup, rats were kept without any medication for 4 weeks and another where rats received saline daily by intraperitoneal injection for 4 weeks. Tramadol Group included 8 rats received the therapeutic dose of tramadol intraperitoneally for 4 weeks. Withdrawal group included 8 rats received the same dose as tramadol group then kept for 4 weeks later without treatment to study the effect of its withdrawal. The obtained specimens were examined by both light and electron microscopy. Results: The control group showed the normal histological picture of the cerebral cortex. The Tramadol group revealed loss of organization of cerebral cortex layers, some pyramidal and granular cells with pyknotic nuclei and surrounded by haloes. Astrocytes showed hypertrophy of their cell bodies with increased thickening of their processes. Ultrastructurally, the pyramidal cells showed heterochromatic nuclei with marked indentations of their membranes and the myelinated axons showed splitting of myelin sheaths with swollen mitochondria in their axoplasm. Withdrawal group showed evidence of improvement as compared to the tramadol group. Conclusion: Opioid analgesics (Tramadol hydrochloride) when the therapeutic dose is used for a long time led to marked damaging effect on the cerebral cortex, However, its withdrawal resulted in improvement to a lesser extent of their damaging effects.
Introduction: Polychlorinated biphenyl (PCB) is considered one of the environmental pollutants. It is used as hydraulic coils in vacuum pumps, pesticides transformers, heat-exchange systems, capacitors and as additives in adhesive inks, paints, plastics, copying paper and sealants. Alpha lipoic acid (ALA) is an antioxidant substance normally present in mitochondria as a coenzyme. Aim of the Work: To evaluate the protective effect of ALA on PCB induced testicular toxicity. Materials and Methods: Twenty five adult male albino rats were used in this study. They were divided into four groups, a control group included 10 rats, group II rats received alpha lipoic acid 25mg/Kg /day orally for 30 days, group III rats received PCB 5mg /Kg/day orally for 30 days and group IV rats received both PCB and alpha lipoic acid at the same previous dose for 30 days. At the appropriate time, the specimens were taken and prepared for light and electron microscope study. Results: LM examination revealed structural alterations in group III in the form of wide spaces between seminiferous tubules that contain homogeneous acidophilic substance, partial or complete detachment of the tubules from the basement membrane and total distorted irregular shaped tubules. Also dilated congested blood vessels were seen. EM examination of this group revealed Sertoli cells with cytoplasmic vacuolation and dilated rER. The basement membrane appeared as thick and irregular line under Sertoli and spermatogenic cells and it was interrupted in some points. Primary spermatocyte appeared shrunken while others revealed vacuoles in the cytoplasm and perinuclear dilatation. Leydig cells showed irregular vacuoles and swollen destroyed mitochondria. Amelioration of the previous histological changes could be detected in group IV. Conclusion: It could be concluded that alpha-lipoic acid has a protective effect against PCB induced testicular toxicity.
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