Digital Repository for Department of Pharmacology & Clinical Pharmacy

يعتبر عقار الالبرازولام Alprazolam من مشتقات البنزوديازيبين benzodiazepine وهو عادة ما يستعمل في علاج حالات القلق, و حالات الهلع المصاحبة للخوف من الأماكن المرتفعة, وأيضا في حالات الإحباط. من ناحية أخري يعتمد تاثير حامض الاسكوربيك Ascorbic acid في الوظائفَ الفسيولوجيةَ بشكل كبير على خاصية الاكسدة والاختزال ,oxido-reduction properties ولكن هناك دلائل مُتزايدة تشيرُ إلي دور مهم جداً لحامض الاسكوربيك Ascorbic acid في وظائفَ الجهاز العصبي المركزي CNSأكثر من كونه عاملِ اختزال اوعامل مساعدِ. فمثلا التأثير علي النشاط العصبي Modulation of synaptic events, النشاط الحركي locomotor activity التأثير في حالةِ الوعي, intermodulation with the consciousness state كلها حقولَ جديدةَ لدراسة نشاطِ حامض الاسكوربيك Ascorbate في الخلايا العصبية. إنّ دورَ glutamate وهو احد السيالات العصبية المحفزة في الدماغ في اضطرابات القلقِ أصبح معترف به أكثر ألان ويسود اعتقاد بان العقار الذي يُنظّمُ وظيفةَ glutamate لَه إمكانية تَحسين و معالجةِ هذه الاِضطراباتِ. وهناك بَعْض الدلائلِ التي تُشيرُ بأنّ glutamate و Ascorbate يرتَبَطان عن طريق عملية heteroexchange, وتقترحُ بأنّ حامض الاسكوربيك Ascorbate قَدْ يَتصرّفُ من خلال نظامِ glutamate للتَأثير على السلوكِ. من هذا المنطلق تَتحرّى الدراسةُ الحاليةُ تأثيراتُ الالبرازولام Alprazolam وحامض الأسكوربيك Ascorbic acid كل علي حدة alone أَو متحدة incombination على سلوكِ القلقِ وعلى مستويات glutamate في مناطقِ منفصلةِ من دماغِ جرذان ويستر البرصاءِAlbino wister rats . كما تدرس تاثير كل منهما علي نشاط العضلات الهيكلية .skeletal muscle activityوقد تمت دراسة التأثير المضاد للقلق anxiolytic effect بإستعمال المتاهةِ المرتفعة المتقاطعة Elevated plus maze, والتأثير على نشاطِ العضلات الهيكلية باستعمال اختبار pull-up test, كما قِيست مستويات الجلوتاميت glutamateفي الدماغِ بإستعمال جهاز كروماتوجرافيا السائلِ العالي الأداءِ High performance liquid chromatography. وتُشيرُ النَتائِجُ المتحصل عليها بأنّ حامضِ الأسكوربيك لَهُ تأثير مضاد للقلق anxiolytic effect يعتمد علي الجرعة ((dose dependent وله تأثيرَ إرخاء للعضلات الهيكلية بدون تأثير منومSedation effect , وقد زادَ حامضِ الأسكوربيك ايضا النشاط الحركي للجرذان .Locomotor activity هذا التأثير المضاد للقلق لحامض الأسكوربيك قَدْ يكون نتيجة تثبيط اطلاق الجلوتاميت glutamate أَو بتحفيز الجابا GABA. كما ان لحامضُ الأسكوربيك أيضاً تأثيرُمضاد للدوبامين Antidopamenergic effect الذي من الممكن ان يُؤثّرُ على السلوكِ. عقار الالبرازولام Alprazolam alone في الجرعةِ المستعملة (2 مج / كيلوجرام) أنتجَ تأثيرَ مضاد للقلق Anxiolytic effect بدون إرخاءِ للعضلات الهيكلية وبدون تاثير منوم effect Sedation. ولَمْ يُؤثّرْ حامضِ الأسكوربيك علي المفعول المضاد للقلق لعقار الالبرازولام عند استعمالهما معا. فالحيوانات عندما عولجتْ بحامضِ الأسكوربيك و عقار الالبرازولام Alprazolam فانهما اظهرا تأثيرا مضافا effect Additive anxiolyticوالذي كَانَ واضحَا عند استعمال الجرعةِ الكبيرةِ لحامضِ الأسكوربيك (500 مج / كيلوجرام). حامض الأسكوربيك لم يَتدخّلُ في عملِ Alprazolam على الجهاز العصبي المركزي CNSولَمْ يُنشّطْ التأثيرَ المركزيَ للالبرازولام Alprazolam فلم يلاحظ أي ثاثير منوم جراء استعمالهما معا. كما ان المعالجة َ بحامضِ الأسكوربيك بالجرعة 125 جم / كيلوجرام أَو 500 جم / كيلوجرام مَع Alprazolam (2 مج / كيلوجرام) أنتجت ْإرخاءَ للعضلات الهيكلية بشكل ملحوظ؛ و هذا قَدْ يكون بسبب تدخلِ حامضِ الأسكوربيك وAlprazolam بآليةِ إنكماشِ العضلةِ الهيكليةِ. كما يمكن ان يكون لحامض الأسكوربيك تأثيرُ مقوي synergestic على Alprazolam كمرخي للعضلات. ومن ناحية اخري اثر حامض أسكوربيك لوحده في مستويات الجلوتاميت glutamate في دماغ الجرذان, حيث زادَ مستويات glutamate في striatum وفي الدماغ المتوسطِ midbrain لكنه انَقصَ هذه المستويات في ساقِ الدماغ brain stem وقشرةِ الدماغ cerebral cortex التي قَدْ تكون بسبب آليةِ heteroexchange للاسكوربيت Ascorbate مَع الجلوتاميت .glutamate استعمال عقار الالبرازولام Alprazolam لوحده زاد بشكل ملحوظ مستوى glutamate في striatum وانَقصَ هذا المستوى في الدماغ المتوسطِ,midbrain الامرالذي يدعو للافتراض بأنّ التأثيرَ المضاد للقلق anxiolytic effect للبنزوديازيبين benzodiazepines لا يُمْكن أنْ يُفسّرَ فقط بواسطة التفاعلِ مع أَو بتحفيز مستقبلات الجابا .GABA وعند استعمال حامض الأسكوربيك مع الالبرازولام فانه لَمْ يَتدخّلُ في تأثير Alprazolam علي مستويات الجلوتاميت glutamate في هذه المناطقِ من الدماغِ لكن بدلاً مِن ذلك اظهرا تأثيراً مماثلاً عندما استعملا سويةً .

Abstract

Alprazolam is a benzodiazepine derivative that is currently used in the treatment of generalized anxiety, panic attacks with or without agoraphobia and depression. The physiological functions of ascorbic acid are largely dependent on the oxido-reduction properties. However, A growing body of evidence indicates for ascorbate a very important role in CNS functioning rather than just fulfilling the relatively passive roles of general reducing agent and enzymatic cofactor. Modulation of synaptic events, locomotor activity, intermodulation with the consciousness state, are new fields of ascorbate activity. The role of glutamate in anxiety disorders is becoming more recognized with the belief that drugs that modulate glutamatergic function have the potential to improve the current treatment of these severe and disabling illnesses. Some evidence indicates that glutamate and ascorbate are linked via a carrier-mediated heteroexchange process suggesting that ascorbate may act through the glutamate system to influence behavior. The present study investigates the effects of alprazolam and ascorbic acid alone or in combination on anxiety behavior and on glutamate levels in discrete brain regions of albino rats. The anxiolytic effect was studied using a plus maze model, skeletal muscle activity effect was scored using pull-up test and brain levels of glutamate were measured using high performance liquid chromatography. The results indicate that ascorbic acid has dose dependent anxiolytic and muscle relaxation effect with out sedation; it also increased spontaneous motor activity by increasing total lines and entries into open and closed arms. Ascorbic acid may exert its anxiolytic action by decreasing glutamate release or by increasing GABA binding. Ascorbic acid showed also antidopamenergic effect which may influence behavior. Alprazolam alone at the dose used (2mg/kg) produced anxiolytic effect without sedation or muscle relaxation. The anxiolytic effect of alprazolam was not affected by ascorbic acid administration. Animals treated with ascorbic acid and alprazolam together showed additive anxiolytic effect which was clear with the large dose of ascorbic acid (500 mg/kg). Ascorbic acid does not interfere with alprazolam action on CNS and did not potentiate the central effect of alprazolam, otherwise sedation would be observed. The combination treatment of ascorbic acid in a dose of 125mg/kg or 500mg/kg with alprazolam (anxiolytic dose) produced significant and dose dependent muscle relaxation as the regaining position time was increased significantly; this may be due to the interference of ascorbic acid and alprazolam with the mechanism of skeletal muscle contraction. Ascorbic acid may have synergestic effect on alprazolam as muscle relaxant. Ascorbic acid alone increased the levels of glutamate in striatum and in mid brain but decreased these levels in brain stem and cerebral cortex which may due to heteroexchange mechanism of ascorbate with glutamate during glutamate uptake. Alprazolam alone incresed significantly the level of glutamate in striatum and decreased this level in mid brain, which may provided a newer mechanism and may supposes that the anxiolytic effect of benzodiazepines can not be accounted for only by the interaction at the GABA A benzodiazepine receptor complex. Ascorbic acid did not modify the alprazolam effect in these brain regions but instead showed similar effect when combined together.
جمال مصطفي علي بن سعد (2007)

Background: The fat extracted from the nut of the African Shea tree (Vitellaria paradoxa) is called Shea butter. It has multiple uses at the local level as it is used in cosmetic products and as a cocoa butter substitute in chocolate industries. It has a high nutritious value and is also a valuable product on the local, national, and international markets, making it the ideal candidate to research and invest in. Aim: This study is a comparative experimental study of the possible burn healing effects between imported South African raw Shea butter and samples in a Libyan market. Method: The control samples were brought from South Africa (Benin traditional markets). A total of 18 different samples were collected from different sale centers in Tripoli, including pharmacies, beauty shops, and spices shops, in addition to one sample brought from Poland. Animal experiment on burn healing effect was carried out on nine male Sprague Dawley (350–400 g) rats aged 6–8 weeks old. After shaving the animal’s dorsum hair, a metal cube was used to create a deep second degree burn wound, and the cube was heated to 100°C for 20 seconds. Medication with Shea butter (control, T1, and T2) was initiated daily for one for these groups by the application of a thin film of the Shea butter samples on the burned areas. On days 1, 3, and 7, the rats were anesthetised and a sample from the burned scar tissue and skin adjacent were evaluated using pathological parameters. Results: The histological study indicates that the use of Shea butter T1 as topical treatment induces an immune response, which enhances the form of the presence of a large number of inflammatory cells in the epidermis and dermis layers. The treatment of burned skin with T2 lasted for 72 hours and it showed slightly significant healing in the normal structure of proliferative granulation tissue with accumulation of fibroblasts and inflammatory cells surrounding the sebaceous glands and hair follicles. Small areas of the epidermis which formed few layers were observed and some hair roots were grown. This was well seen in cases of T1 and T2. Shea butter bought as raw might have a bad effect on burned skin. Conclusion: Shea butter bought as raw might have bad effect on burned skin. On the other hand, the sample from Poland had a therapeutic effect, which was because of the additives such as avocado oil, grape seed oil, and others. arabic 18 English 101
Sakina Salem Mohammed Saadawi, Soad Ali Abdulsalam Treesh, ٍSuhera Mehemed Abdulsalam Aburawi, , , (11-2020)

Caffeine has dose-dependent effects on mood, attention, and physiology. Behavioral effects of caffeine in humans have also been well documented. This article aimed to study the effect of different caffeine concentrations on behavior and motor activity of mice. The experiments was carried out using 24 male mice (25-30gm). Plus maze was used for screening of antianxiety effect of caffeine. While swimming maze was used to test antidepressant effect. Statistical analysis were performed using computer program SPSS (version 22). At dose of 100 mg/kg, caffeine acted as anxiolytic compound. Caffeine increased motor activity at dose of 25mg/kg and decreased motor activity at dose of 200mg/kg. At dose of 100mg/kg, caffeine acted as antidepressant. In conclusion, caffeine can act as stimulant, while in over dose it acts as depressant. Caffeine showed to have anxiolytic effect in certain doses. arabic 14 English 91
Sakina Salem Mohammed Saadawi, ٍSuhera Mehemed Abdulsalam Aburawi, SUMAYA ESEDEEG ABDALLAH BAAIO(4-2018)

Caffeine is the most commonly used psychoactive substance throughout the world. It is found in coffee, black tea, and chocolate, as it is produced naturally in the beans and leaves of the plants used to manufacture these products. This study aimed to make a survey study among children 2-11 years in some Tripoli, Libya schools to determine caffeine concentration in number of beverages and foods consumed by studied children. About 313 copies of the questionnaire were distributed to students to be filled by their parents. Caffeine was extracted from samples using dichloromethane. Purity of isolated caffeine was estimated by using TLC method.Quantitative analysis of caffeine was performed by using a UV-Visible spectrophotometer. Chocolate biscuits, chocolate cake, cocoa milk and chocolate ice cream were the highest consumed products among the studied children (81%, 79%, 67% and 63% respectively). The highest side effects of caffeine consumption was hyperactivity was the highest side effect in children (76%). Some children also suffered from severe side effects such as panic attack (14%). Naseem ice cream sample showed the highest caffeine content (28 mg/serving) among solid samples.Whereas in the beverages, energy drink samples Red pull, XIR and Shark were 268, 262 and 250 mg/serving respectively. In conclusion, there was excessive consumption of caffeine among the studied group of children and some of them showed side effects and even severe side effects. Variety of tested foods and beverages under the study contained uncontrolled concentrations of caffeine. In addition, chocolate milk (Al Rayhan), contained no caffeine. arabic 15 English 97
Sakina S. Saadawi, Khairi A. Alennabi, AMAL .A ABOALLA AMMAR, , , ٍSuhera Mehemed Abdulsalam Aburawi(9-2019)

Aims: This article aimed to study the effect of different caffeine concentrations on behaviour and motor activity of mice. Place and Duration of Study: This study took place in Faculty of Pharmacy, University of Tripoli, and was conducted between 2017 to 2018. Methodology: The experiment was carried out using 24 male mice (25-30 gm). Plus maze was used for screening antianxiety effect of caffeine. While swimming maze was used to test the antidepressant effect. Descriptive statistics was performed using SPSS (version 22), followed by one sample Kolmogorov-Simirnov test. One-Way ANOVA was applied to compare between groups and Post Hoc test (LSD). Results: At a dose of 100 mg/kg, caffeine produce significant decrease in the duration of immobility using forced swimming maze; while the lower (25 mg/kg) and the higher (200 mg/kg) doses did not produce any changes compared to the control. In plus maze, Caffeine decreases the anxiety measure at the dose used of 100 mg/kg; but did not change the anxiety measure when lower (25 mg/kg) or higher (200 mg/kg) doses used compared to the control. The spontaneous motor activity was decreased significantly after administration of the higher dose of 200 mg/kg; the lower dose (25 mg/kg) showed insignificant increase, while the dose of 100 mg/kg produce insignificant decrease in the spontaneous motor activity. Conclusion: Caffeine has dose dependent effect, in a dose 100 mg/kg it produce anxiolytic and antidepressant like action, while lower (25 mg/kg) and higher (200 mg/kg) doses did not show any changes. Caffeine also produce dose dependent decrease in the spontaneous motor activity, this indicate that caffeine produce CNS depression with higher doses. arabic 12 English 73
Sakina S. Saadawi, Khairi A. Alennabi, Sumaya Baayo, Amera Fares, Najwa Alosta, Suher M. Aburawi(3-2020)