Qassim University

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    Comparative Evaluation of Doxorubicin, Cyclophosphamide, 5-Fluorouracil, and Cisplatin on Cognitive Dysfunction in Rats: Delineating the Role of Inflammation of Hippocampal Neurons and Hypothyroidism
    (Saudi Digital Library, 2023-10-10) Alotayk, Lamis Ibrahim; Aldubayan, Maha; Alhowail, Ahmad
    يعتبر العالج الكيمائي هو واحد من الوسائل األساسية في عالج المرضى المصابين بالسرطان ؛ على الرغم أن معظم المرضى ربما يعانون من ضعف مؤقت في االدراك و الذاكرة. يعتبر دواء الدوكسوروبيسين ، سيكلوفوسفاميد، -5 فلورواسيل، و سيسبالتين من العالجات المستخدمة في العالج الكيميائي لمعالجة أنواع السرطان المختلفة و التي اثارها السلبية و مضاعفاتها على المرضى هي ضعف االدراك و الذاكرة المؤقت نتيجة العالج الكيميائي فيما يعرف بالدماغ الكيميائي . الدماغ الكيميائي اثر على ما يقارب %75 من الناجين من السرطان و اللذين ليس امامهم بديل عالج. تهدف هذه الرسالة إلى مقارنة تأثير العالجات الكيميائية المختلفة )الدوكسوروبيسين ، سيكلوفوسفاميد، -5فلورواسيل، و سيسبالتين ( المستخدمة و المتزامنة مع نقصان االدراك المؤقت مع دراسة الياتها المحتملة باستخدام نماذج الجرذان. تم تقسيم الجرذان إلى سته مجموعات مع وضع عشرة في كل مجموعة. بعد ذلك تم حقن الجرذان مرة واحده فقط في منطقة الغشاء البريتوني بواسطة 25 مغ/ كغم دوكسوروبيسين ، 200 مغ / كغم سيكلوفوسفاميد، 100 مغ / كغم -5فلورواسيل، و 8 مغ / كغم سيسبالتين . وظلت المجموعة األخيرة بدون حقن و تسمى المجموعة المتحكمة. الختبار المهام المعتمدة على الحصين و هي تشمل متاهة Y ، التعرف على األشياء الجديدة ) NOR )، واختبار المتاهة الموجبة المرتفعة )EPM). و كذلك تم جمع عينات الدم و المخ لجميع مجموعات الجرذان و العمل على تقييم عالمات تأثر تسمم القلب و هرمونات الغدة الدرقية و عالمات االلتهاب.
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    Protective Effect of Galantamine against Doxorubicin-Induced Neurotoxicity
    (Qassim University, 2023-09-06) Alsikhan, Rawan; Aldubayan, Maha
    Background and aims: Doxorubicin (DOX) causes cognitive impairment (chemobrain) in patients with cancer. While DOX damages the cholinergic system, few studies have focused on the protective effects of cholinergic function on chemobrain. The acetylcholinesterase inhibitor galantamine (GAL) demonstrates neuroprotective properties. We investigated the mechanisms associated with DOX-induced cognitive impairments and the potential protective role of GAL in preventing chemobrain. Main methods: Female Wistar rats were divided into control, DOX, GAL, and DOX + GAL groups. The rats in the DOX group were administered DOX (5 mg/kg intraperitoneally twice weekly for two weeks), while those in the GAL group were orally administered GAL (2.5 mg/kg) via oral gavage once daily for 15 days. The combination group (DOX + GAL) received GAL (once daily) and DOX (two times per week) concurrently. The body weights and survival rates were monitored daily. The animals were subjected to behavioral tests to assess the memory function followed by the biochemical estimation of inflammatory markers, including tumor necrosis factor-α (TNF-α), interleukine-1β (IL-1β), and interleukine-6 (IL-6) in rat brain tissue and RT-qPCR. Key findings: DOX caused a reduction in the body weight and survival rate, which was alleviated by GAL concomitant treatment with DOX (DOX + GAL). These groups had reduced body weights and survival rates. DOX-treated animals exhibited an impairment of short-term spatial working memory, manifested as a behavioral alteration in the Y-maze test, the novel object recognition (NOR) test, and the elevated plus-maze (EPM) test. Concurrent treatment with GAL (DOX + GAL) showed improved memory function, as evidenced by an increase in the number of entries and time spent in the novel arm, the time spent exploring the novel object, and the transfer latency in the Y-maze, NOR test, and EPM test, respectively. These findings were also supported by biochemical observations showing the reversal of DOX-induced changes in IL-1β, IL-6, and TNF-α, as well as their relative expression of mRNA in brain tissue following concurrent GAL treatment. Conclusion: GAL appeared to be a neuroprotective agent against neuroinflammation caused by DOX by reducing inflammatory markers in the brain.
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    Effect of Ajwa Dates Seeds Methanolic Extract on Type-2 Diabetes Mellitus-Induced Memory Deficit in Rats
    (Saudi Digital Library, 2021) Alharbi, Hindi Salem Rashed; Kumarasamy, Vasudevan Mani
    Background and purpose: Diabetes mellitus (DM) is a highly prevalent metabolic disorder that affects children, adults, and the elderly and causes various physiological complications. One of its pathological impacts is brain dysfunction, especially memory and cognitive decline. The present study aimed to explore the impacts of methanol extract of Ajwa dates seeds on type 2 diabetes mellitus-induced memory deficits using a rat model. Methods: A total number of 36 male Sprague Dawley rats (3 months old; 200-250 g body weight) was used and randomly assigned into six groups, and each group comprised six rats. Type 2 diabetes was induced in five groups by nicotinamide (120 mg/kg, i.p.) followed by streptozotocin (60 mg/kg, i.p.), and the non-diabetic group was considered as a control. The animals were treated with vehicle (0.5 % w/v CMC), a standard drug metformin, and three different doses (100, 200, 400 mg/kg) of methanolic Ajwa date seeds extract (MASE) for 30 days. During the last five days (26th to 30th days) of drug treatment, behavioral tests such as elevated plus maze (EPM), Y-Maze and Novel object recognition (NOR) were carried out. On the 30th day of treatment, all animals were sacrificed; blood samples and brain homogenates were collected for further biochemical assessment. The blood glucose and plasma insulin levels were estimated to confirm the anti- diabetes functions of extract. From brain homogenate, the acetylcholine (ACH) and neuroinflammatory parameters [cyclooxygenase 2 (COX 2), tumor necrosis factor alpha (TNF-α), interleukin (IL)- 6 & 10 and transforming growth factor beta 1(TGF-ẞ1)] were analyzed. Results: Diabetic-induced rats showed memory impairment in all the behavior models by increasing transfer latency (TL) in EPM, decreasing number of entries to the novel arms in Y-maze and time spend to explore the novel object in NOR. The results of the EPM test showed that the treatment of MASE (100, 200 and 400 mg/kg, p.o.) significantly enhanced (p<0.01) transfer latency (TL) as compared to diabetic-induced animals. Additionally, the high doses (200 and 400 mg/kg, p.o.) of MASE improved the performance (p<0.05) on number of entries to the novel arms in Y- maze and time spend to explore the novel object in diabetic-induced rats using NOR tasks, respectively. In biochemical estimations, treatment of MASE (100, 200 and 400 mg/kg, p.o.) significantly (p<0.001) reversed the blood glucose levels in the diabetic experiment model. On the other hand, the insulin activity increased (p<0.001) with treatment of MASE (200 and 400 mg/kg, p.o.). The MASE improved cholinergic activity in the CNS through elevating ACh levels in diabetic-induced rats. Regarding neuroinflammation, administration of MASE decreased (p<0.01) proinflammatory cytokines (TNF-a and IL-6) levels at all the doses (100, 200 and 400 mg/kg, p.o.) and increased (p<0.05) anti-inflammatory cytokines (IL-10 and TGF-B1) at selected doses. Conclusion: The overall results supported that MASE could reverse the cognitive impairment induced by type-2 diabetes by inhibiting the neuronal inflammation and increasing the ACh levels. It is concluded that these beneficial effects of the extract may be a potential treatment to handle the cognitive deficits in diabetic patients.
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