Department of Pharmacology and Toxicology

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    Effect of Ethanolic Extract of Punica granatum Peel (L.) (Rummon) on Some Biochemical and Histopathological Parameters in Albino
    (University of Khartoum, 2020) Arwa Mahjoub El Harith Mohammed
    Abstract: People for millennia have used plants as medicine. Most of Sudanese in rural areas rely on traditional medicine for treatment of many diseases; however, there is a lack of proven scientific studies on the toxicity and adverse effect of these treatments. Therefore, this study was designed to investigate the toxicity of ethanolic extract of Punica granatum peel in albino rats by measuring liver and kidney functions parameters in addition to glucose and body weight. 24 albino rats of both sex were randomly arranged into 4 groups each of 6 rats .Group 1 served as untreated control; groups 2,3 and 4 were treated with daily oral doses of ethanolic extract of Punica granatum ( 250, 500 and 1000 mg/kg bw) respectively; all treatments continued for 4 weeks. Rats were weighed and blood samples were collected for measurement of serum biochemical parameters at days zero, 14 and 28. Parameters measured for studying toxicity of the extract included liver function parameters and kidney function parameters; AST, ALT, urea, creatinine, total protein and albumin, in addition to blood glucose level, Body weight, body weight gain and organ weight to body weight ratio. Sections of liver, kidney, heart and spleen were taken for histopathology at day 28. The design of statistical analysis was (ANOVA).The results of biochemical analysis showed that the lower doses of the ethanolic extract (250 and 500 mg/kg) revealed no significant changes in all liver and kidney function parameters throughout the experimental period .While the higher dose of ethanolic extract (1000 mg/kg) scored significant (P ≤0.05) increase in urea and ceratinine especially at day 28 of experiment .The blood glucose level recorded significant (P ≤0.05) decreases in all treated group at day 28. In addition, the weight, of liver, Kidney, heart and spleen of all groups presented no significant changes when compared with the control group at the end of experiment. The results of histopathological sections of liver, kidney, heart and spleen in rats treated with 250and 500 mg/kg of the extract showed no pathological changes while the kidney sections of rats treated with 1000mg /kg showed shrinkage glomeruli and limited areas of necrosis, and the liver and spleen showed fatty change and congestion respectively, while the heart muscle demonstrated no pathological changes. It is concluded that the exthanolic extract of the peels of prperation revealed no toxic effect with oral administration at 250 and 500 mg/kg bwt in albino rats, while the higher dose (1000 mg/kg bwt) produced nephrotoxicity. Also it is concluded that, the ethanolic extract of Punica granatum peel at 250,500 and 1000 mg/kg, possess hypoglycemic properties. The study recommended that, the ethanolic extract of Punica granatum peel should not be used for therapeutic purposes at dose of (1000) mg/kg as it leads to nephropathy. المستخـلص : يستعمل الأنسان النباتات الطبية منذ قديم الزمان . يعتمد معظم السودانيين فى المناطق الريفية على الطب الشعبى فى علاج كثير من الامراض ونسبة لعدم توفر الدراسات العلمية لُسُمية كثير من هذه النباتات ،اُجريت هذه الدراسة لتقويم سُمية المستخلص الإيثانولى لقشر الرمان على الفئران البيضاء.بواسطة قياس وظائف الكلى والكبد وأيضاٌ قياس سكر الدم ووزن الجسم . أجريت التجربة على24 فارا ً ابيضا ًمن الجنسين تم تقسيمها عشوائيا ً الى 4 مجموعات كل مجموعة تحتوى على 6 فئران . استمرت التجربة 4 أسابيع. المجموعة الأولى خُصصت كمجموعة الشاهد وأعُطيت المجموعة الثانية والثالثة والرابعة المستخلص الأيثانولى لقشر الرمان بجرعات يومية عن طريق التجريع بمعدل 250 و500 و1000 ملجم /كجم على التوالى تم قياس الوزن للفئران وجمعتُ عينات الدم لأجراء المعايير البيوكيميائية وذلك قبل التجريع , وفى اليوم 14, 28 يوم من التجربة .شملت قياسات تقييم السمية قياسات الكبد والكُلُى، وتشملAST, ALT ,Urea ,Creatinine,Total protein , Albumin, تم أيضآ قياس الجلكوز ووزن الجسم والزيادة فى الوزن ونسبة وزن الأعضاء الى وزن الجسم تم اخذ عينات من الكبد ,الكُلى , القلب ,الطحال لإجراء فحص الانسجة المرضية وذلك عند نهاية التجربة ،طريقة التحليل الإحصائى المتبعه فى تحليل النتائج كانت طريقة المتغير الواحد(ANOVA).أظهرت نتائج الفحوصات البيوكيميائية أن الجرعات المنخفضة من المستخلص الايثانولى ( 500,250 ملجم /كجم ) لم تحدث أى تغييرات سّمية معنوية فى كل قياسات وظائف الكبد ووظائف الكُلى طول فترة التجربة , أما الجرعة الأعلى (1000 ملجم /كجم ) من المستخلص الإيثانولى سُجلت زيادة معنوية (P≤0.05)بالنسبة لقياسات للكيراتنين واليوريا خاصة فى اليوم 28 من التجربة. سجلت قياسات الجلكوز نقصانا ً معنويا ً (P≤0.05) فى كل المجموعات فى اليوم 28 . وزن الكبد , الكُلى , القلب والطحال فى كل المجموعات لم تظهرأى تغيير معنوى عندما تم مقارنتها مع مجموعة الشاهد عند نهاية التجربة. لم تظهر نتائج الفحص النسيجى المرضى فى أنسجة الكبد ، الكلى ، الطحال والقلب أى تغييرات مرضية فى الجرعات 250, 500ملجم /كجم بينما أظهرت أنسجة الكلى فى الجرعة 1000ملجم /كجم إنكماشا ً فى أنيبيبات الكلى وموت فى بعض من الخلايا الكلوية ،كما أظهرت أنسجة الكبد والطحال تغيرا ً دهنيا ً وإحتقانا ً على التوالى كما لم تظهر أنسجة القلب أى تغييرات مرضية. خلصت الدراسة إلى أنه لايوجد أثر سام للمستخلص الإيثانولى لقشر الرمان عند التجريع الفموى بالجرعات 500,250 ملجم /كجم بينما احدثت الجرعة الأعلى 1000 ملجم /كجم سُمية كُلوية . ايضآ خلصت الدراسة الى ان المستخلص الإيثانولى بالجرعات 500,250,1000 ملجم /كجم من قشر الرمان تحتوى على عناصر خافضة لمستوى الجلكوز فى الدم. تُوصى الدراسة بعدم إستعمال المستخلص الإيثانولى لقشر الرمان بالجرعة 1000 ملجم /كجم لإى أغراض علاجية إذ انه يؤدى الى سُمية كلوية .
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    Effect of Ethanolic Extract of Hyphaene thebaica (Doum) Fruit Pulp on Nephrotoxicity Induced by Mercuric Chloride in Rats
    (University of Khartoum, ) Abdalla, Elham Alsayed Merghani ; Samia Mohammed Ali El Badwi ; Department of Pharmacology and Toxicology
    This study was designed to investigate the nephroprotective effects of ethanolic extract of the Hyphaene theabica L Mart (Doum) fruit pulp against mercuric chloride induced nephrotoxicity in rats. Phytochemical screening was done for the ethanolic extract of H.theabica. Twenty four Wistar albino rats were randomly arranged into 4 groups, each of 6 rats, group 1 served as control, group 2 (treated control) was treated with a single oral dose of mercuric chloride 1mg/kg B.W/day, groups 3 and 4 were treated with mercuric chloride as in group 2, in addition they were treated simultaneously and orally with a single doses of the ethanolic extract of H.theabica at 250, 500 mg/kg B.W/day, respectively. All doses were continued for 28 days. Rats were weighed and blood samples were collected on days 0, 14 and 28 for measurement of kidney function parameters (urea and creatinine) and biochemical parameters (albumin and total protein). At the end of the experimental period rats kidneys were weighed and specimens were taken for histopathology. The results of phytochemical screening revealed presence of flavonoid, alkaloid, tannin and coumarin. The results of nephrotoxicity in mercuric chloride group (Group 2) showed significant increase (p < 0.05) in concentration of serum urea and creatinine and decrease in the total protein and albumin compared to the control group. The result of nephroprotective groups (groups 3 and 4), revealed significant(p < 0.05) improvement of the previous parameters indicated by, decrease in the serum urea and creatinine and significant(p < 0.05) increase in total protein and albumin compared to the treated control (group2).The histopathological results of the kidney sections of mercuric chloride group demonstrated glomerular and tubular necrosis with desquamation of the tubular epithelial cells of the renal cortex while the groups treated with H.thebaica revealed significant amelioration of kidney damage evidenced by mild congestion and mild fatty changes of the renal tubules. The heamatological picture showed significant (p < 0.05) decrease in hemoglobin concentration and MCHC in group 2, the same parameters were significantly (p < 0.05) increased in H.thebaica treated groups while no significant changes were detected in RBCs, PCV and MCV. Body weight gain and kidney weights were significantly decreased in the intoxicated group while they were significantly improved (p < 0.05) in the treated groups. In conclusion, the ethanolic extract of H.thebaica fruits pulp at doses 250, 500 mg/kg B.W on nephrotoxicity induced by mercuric chloride in rats, exhibited significant nephroprotective effects. The recommendation of this study, focused on isolation and identification of the active components in H.thebaica that were responsible for nephroprotective activity.
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    In vitro Assessment of Acaricidal Activity of Hot water Extract of Citrullus colocynthis (Alhandal) Fruit, Azadirchta indica (Neem) leaves and Allium sativum (Garlic) Cloves against Hyalomma anatolicum larvae
    (University of Khartoum, ) Mohamed, Asma Gibril Eljack ; Khadiga Mohamed Osman Abdallah ; Pharmacology and Toxicology
    This study was conducted to assess the acaricidal activity of the hot water extract of Citrullus colocynthis fruit, Azadirachta indica leaves and Allium sativium cloves against Hyalomma anatolicum larvae. The three plants were collected from khartoum and were authenticated by botanist in the Medicinal and Aromatic Plants Research Institute. (MAPRI), Khartoum. The materials of plants were dried in shaded ventilated area at room temperature for one week before grinding to powder for extracted. Phytochemical analysis for active ingredients from hot water extract of three plants was carried out on the Department of Chemistry in (MAPRI). Engorged female ticks were collected from naturally infested cattle in Elgreif west dairy farms and were identified as H.anatolicum in the Department of Entomology and Ticks, Central veterinary Research Laboratory (CVRL) .Ticks were kept in desiccators over saturated sodium chloride solution to provide 75-80% relative humidity (RH) .The desiccator was maintained in an incubator at 27±1οC to provide optimum conditions for oviposition. Different concentrations (40%, 20%, 10% and 5%) of plants extracts were prepared and the control solution was set up with distilled water. Three to Five hundred ,12-14 days old unfed larvae of H.anatolicum were used to evaluate the acaricidal activity of the candidate plants extract using Larval Immersion Test (LIT), for 48hr after which alive and dead larvae were counted and calculate the larvae mortality rate corresponding to each concentration used. If there was mortality in the control group more than 5% larval percentage rates achieved were corrected. Data were expressed as mean ± SEM and were compared using X one-way ANOVA. The results of phytochemical analysis of the three plants showed the presence of flavonoids, alkaloids, cumarins, tritrepens saponins, and anthraquinone glycosides, tannins (absent in C. colocynthis) and steroids (absent in Allium sativum). The hot water extracts of Citrullus colocynthis fruit , Allium sativum cloves, and Azadirchta indica leaves showed toxicity against H.anatolicum larvae , there was significant (p<0.05) high mortality rate of larvae in high concentration (40%) was 80.9%, 67.8% and 16.8% respectively. It was concluded that the hot water extracts Citrullus colocynthis fruit Allium sativum cloves, and Azadirchta indica leaves of proved to have larvicidal efficacy with the mortality rates increased with increasing concentration of extracts, with C.colocynthis having the best acaricidal activity among others. I was recommended conduct further studies during other life cycle stages of Hyalomma anatolicum and use other types of plant extracts. The study also recommended develops these plants to be in use as acaricidal agents replacing chemical drugs to minimize their adverse effects on host and environment.
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    Phenotypic and Molecular Identification of Albendazole Resistant Haemonchus contortus in Goats in South Darfur State, Sudan
    (University of Khartoum, ) Adam, Khalid Mohammednour Mohammedsalih ; Amna Eisa Khallafalla ; Pharmacology and Toxicology
    The present study aimed to evaluate albendazole resistance status of Haemonchus contortus in experimentally and naturally infected goats in different study areas of South Darfur State, Sudan, based on two hypotheses. The first indicated the change of albendazole efficacy is due to treatment failure as the result of under-dosing, while the second hypothesis indicated the actual development of resistance. Resistance to albendazole was evaluated using two different doses, 5 or 10 mg/kg body weight, and in different seasons during August 2014 – January 2017, based on phenotypic and molecular techniques. The obtained results were statistically analysed using NCSS and eggCounts package in R software. Four experimental infection trials were conducted during winter and summer using different H. contortus isolates that were derived from Nyala, Kass, Um Dafuq and Tulus. In each trial, 16 male goats, 3 – 6 months old, were infected individually with a single dose of 150 infective H. contortus larvae (L3)/kg body weight, then half were treated with 5 mg/kg. Also, resistance to albendazole was evaluated in goats naturally infected with gastrointestinal nematodes at Nyala and Beleil in autumn and winter. In these trials, 88 goats treated with 5 mg/kg, and 35 received 10 mg/kg dose. Assessing the resistance status at phenotypic level was depended on the faecal egg count reduction test (FECRT), the egg hatch test (EHT) and coproculture examination using samples collected on day 0, 8 and 14. Albendazole resistance is considered when the FECRT result is less than 95% and the effective concentration 50 (EC50) of the EHT is higher than 0.1 µg/ml thiabendazole, as recommended by the World Association for the advancement of Veterinary Parasitology. Molecular techniques were used to detect the presence of mutations at codons 167 (TTC/TAC), 198 (GAA/GCA) and 200 (TTC/TAC) in β-tubulin isotype 1 gene using 34 samples of H. contortus including L3 and adult worms. The techniques used were PCR, gene sequencing, gene cloning and pyrosequencing assays. The results of the FECRT as well as the EHT obtained from experimental and natural infection trials, and in different seasons, showed for the first time that albendazole resistant H. contortus are present in goats in South Darfur. With 5 mg/kg dose, the efficacy was 62, 71, 72 and 79% to H. contortus isolates from Nyala, Um Dafuq, Kass and Tulus, respectively. The EC50 of these trials was in a range of 0.11 – 0.18 µg/ml thiabendazole. In Nyala natural infection trials, the FECRT indicated percent reductions of 74% to 5 mg/kg and of 86% to 10 mg/kg dose. In Beleil, albendazole was 95% effective. The calculated EC50 ranged from 0.17 to 0.23 µg/ml thiabendazole in Nyala, while in Beleil was 0.06 µg/ml. No significant differences (P<0.05) detected when resistance evaluated in different seasons. The species-specific PCR detected H. contortus, Trichostrongylus colubriformis and Cooperia punctata in L3 samples collected from goats treated with 5 or 10 mg/kg body weight. The results of molecular tests showed no evidence for the presence of resistance-related alleles at codons 167 and 200. However, at codon 198 the sequencing results successfully showed the presence of two new candidates, i.e. replacement of wild-type glutamate with either leucine (E198L) (82%) or valine (E198V) (12%). These candidates have never been described before in H. contortus. It can be concluded that H. contortus has developed resistance to albendazole in South Darfur State. Additionally, this work elucidates the genetic information of albendazole resistance in H. contortus in Sudan with establishment of two new candidates, E198L and E198V. The study recommends the change of manufacturer package labels of albendazole to be used at 10 mg/kg body weight in goats in Sudan. The next steps of worm control in South Darfur will involve evaluation of target selective treatment, e.g. FAMACHA system, to decide which animals require treatment and identifying where there is resistance so that a change of anthelmintic from albendazole to, e.g. levamisole can be made.
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    Effects of Ambrosia maritima (Damsissa) on Anaemia Related Parameters in Rabbits
    (university of khartoum, ) Alhassan, Marwa Hassan Alfadol ; Osama Hassan Ahmed
    : The study was carried out to investigate the anti- anaemic activity of traditional medicinal plant, Ambrosia maritima (Damsissa) ethanolic extract in phenylhydrazine hydrochloride-induced anaemia in rabbits. Twenty five adult rabbits were equally divided into 5 groups. Anaemia was induced by subcutaneous administration of phenylhydrazine hydrochloride at a dose of 30 mg/kg body weight and maintenance dose of 15 mg/kg body weight in all groups except group (A) (control group).On day 8 of administration of phenylhydrazine, the ethanolic extract of Ambrosia maritima was orally administered to groups B, C, D at the rate of 250, 500, 1000 mg/kg body weight respectively, meanwhile group E was left as phenylhydrazine control group (phenylhydrazine without Ambrosia maritima). The experiment continued for 30 days during which, blood samples were collected on day 0, 7, 14, 22, 30 for heamatological examinations and serum analysis. The haematological parameters investegated included total erythrocytes count (TEC), Packed cell volume (PCV), Mean corpuscular volume (MCV), Mean corpuscular haemoglobin (MCH), Mean corpuscular haemoglobin concentration (MCHC), total leukocytes count TLC and differential leukocyte count. Serum biochemical tests included Fe concentration, total lipid, total protein, cholesterol and blood glucose level. The results of the haematological tests revealed significant (P<0.05) increase in Hb, TEC, PCV, TLC and the ratios of lymphocytes, monocyte and basophilsand significant (P<0.05) decrease in MCV, MCH, eosinophils and neutrophil in response to Ambrosia maritima ethanolic extracts.No significant changes were observed in MCHC and blood glucose level. The results of serum metabolites revealed significant (P<0.05) increase in total lipid and Fe concentration and significant (P<0.05) decrease in cholesterol level. No significant changes were observed in Total protein values in response to Ambrosia maritima treatment.Ambrosia maritima ethanolic extract orally had no toxic effect at the different doses used in this study (250,500 and 1000 mg/kg body weight).The data demonstrated that Ambrosia maritima had anti-aneamic effect. Further Studies are needed to investigate the effect of Ambrosia maritima by other methods of extraction at higher doses and for a longer period of time using different routes of administration