SPRAGUE DAWLEY RATS

INFLUENCE OF ANTIHYPERTENSIVE DRUGS AND ANTIOXIDANTS ON PLATELETS AND ENDOTHELIAL FUNCTIONS OF SALT-INDUCED HYPERTENSION IN SPRAGUE DAWLEY RATS

Year of Publication
Publication Type
Abstract
High salt consumption is known to be detrimental to cardiovascular health and can lead to various problems. However, the effects of antihypertensive drugs and antioxidants on salt-induced vascular
dysfunction remain insufficiently explored. This study aimed to examine the influence of antihypertensive drugs and antioxidants on impact of salt-loading in platelet and endothelial function. Forty-eight male Sprague-Dawley rats were assigned to control group and different test groups receiving a high salt diet with different antihypertensive drugs and antioxidants interventions. The control group received a normal rat chow (0.3% NaCl) and water, the high salt (HS) group received rat chow containing (8% NaCl), others were fed on high salt diet (8% NaCl) with interventions including Lisinopril 2.3mg/kg/d, Losartan 0.1mg/kg/d, Verapamil 0.1mg/kg/d,m Vitamin C 100mg/kg/d, Magnesium 4.8mM and Kolaviron 200mg/kg/d. Drug administrations were by oral gavage. Blood pressure (mmHg) and heart rate (bpm) were monitored using the cufftail artery method. At the end of 8 weeks treatment period, animals were sacrificed using
chloroform anaesthesia, carefully, the abdominal cavity was cut open by mid-line incision using a clean dissecting set. Left ventricle, aorta and mesenteric artery were harvested and blood samples were collected for platelet count, platelet indices and gene protein expression analyses. The result showed a significant increase in the mean arterial pressure, systolic and diastolic pressure in saltloaded rats compared with control, the high salt + Lisinopril, Losartan, Verapamil, Vitamin C,
Magnesium and Kolaviron groups showed significant reduction in blood pressure compared with high salt group. There was a significant increase in platelet activating factor (PAF) gene expression
in high salt group compared with control. High salt co-treated with Lisinopril, Losartan, Verapamil, Vitamin C, Magnesium and Kolaviron groups showed significant decrease in PAF gene expression compared to high salt group. There were no significant changes in platelet count across groups compared with control. There was a significant decrease in mean platelet volume in HS + Lisinopril and HS + Verapamil groups compared with control but there were no significant changes in all the other groups compared with control. There were no significant changes in plateletcrit in all the groups compared with control. There were no significant changes in platelet distribution
width in all the groups compared with control. There was significant decrease in platelet large cell ratio in HS + Lisinopril, HS + Verapamil and HS + Kolaviron groups compared with control but
there were no significant changes in all the other groups compared with control respectively. In conclusion, this study provides evidence that suggests that high salt diet may alter platelets function through oxidative, and protein enzyme receptor pathways which may be explored for improvement in therapeutic interventions.
Supervisor(s)
co-supervisor

EFFECTS OF SALBUTAMOL, MOTELUKAST AND HYDROCORTISONE ON LUNG HISTOLOGY AND ANTIOXIDANTS IN ASTHMA INDUCED SPRAGUE DAWLEY RATS

Year of Publication
Publication Type
Abstract
The aim of this study is to understand the significance of montelukast, hydrocortisone and salbutamol on the lung histology and antioxidant levels in asthma induced Sprague Dawley rats. Chronic asthma is a respiratory disease characterized by oxidative stress and inflammation of the airways. Montelukast, hydrocotisone and salbutamol are drugs that are often used to treat asthma. Their impact on endogenous antioxidant levels in asthmatic conditions are yet to be clearly defined. Medication for asthma might include corticosteroids (like hydrocotisone), leukotrine receptor antagonists (like Montelukast) and Beta 2-adrenergic receptors (like salbutamol). Free radicals may be neutralized by antioxidants, which also lessen oxidative stress in the body. As a selective antagonist of the leukotriene D4 (LTD4) receptor, montelukast acts by preventing the body's production of leukotrienes, which are substances that promote inflammation and constriction of the airways when they come into contact with allergen. Other classes of drugs also prove useful in bronchodilation. Five (5) primary groups of Sprague Dawley rats were grouped (control, negative control and test groups). Group 1 control was not induced with asthma, Group 2, negative control was induced with asthma but not treated. These two groups make up the control group. Group 3 was induced with asthma and
treated with salbutamol, Group 4 was induced with asthma and treated with montelukast, while Group 5 was induced with asthma and treated with Hydrocortisone. These three groups make up the test group, five rats in each group. The rats were sensitized to 1mg ovalbumin and 20mg Aluminium hydroxide dissolved in 0.9 saline, and then they were challenged with ovalbumin 1 % w/v adsorbed in 0.9 saline, twice weekly for four weeks (28 days), using a Medal family nebulizer. This caused the rats to develop asthma. After the Conclusion of treatment, the rats were sacrificed and their lungs were extracted for histological assay, while 1ml of blood is extracted for measurement of antioxidants using the spectrophotometric method, following reagent manufacturers guidelines. Measurements were made of the amounts of endogenous antioxidants, such as glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH). The findings demonstrated that there was statistically significant increase in superoxide dimutase and malondialdehyde levels in the negative control in comparison to the control group, while there was a statistically significant decrease in catalase and glutathione levels in the negative control group in comparison to the control group. Super-Oxide Dismutase was considerably increased after treatment with all classes of drugs. There was no statistically significant variance in catalase level noticed among the test group. Glutathione peroxidase was only significantly in the group treated with salbutamol, it showed no significant variance in other drug administration. There was significant increase in malondialdehyde in all groups except salbutamol. All test groups had considerably lower glutathione levels than the control group. As a result, the research concludes that some antioxidant levels (except glutathione) can be significantly
increased with the given drugs, reducing oxidative stress in lung tissues.
Supervisor(s)
co-supervisor

INFLUENCE OF ANTIHYPERTENSIVE DRUGS AND ANTIOXIDANTS ON PLATELETS AND ENDOTHELIAL FUNCTIONS OF SALT-INDUCED HYPERTENSION IN SPRAGUE DAWLEY RATS

Year of Publication
Publication Type
Abstract
High salt consumption is known to be detrimental to cardiovascular health and can lead to various problems. However, the effects of antihypertensive drugs and antioxidants on salt-induced vascular dysfunction remain insufficiently explored. This study aimed to examine the influence of antihypertensive drugs and antioxidants on impact of salt-loading in platelet and endothelial function. Forty-eight male Sprague-Dawley rats were assigned to control group and different test groups receiving a high salt diet with different antihypertensive drugs and antioxidants
interventions. The control group received a normal rat chow (0.3% NaCl) and water, the high salt (HS) group received rat chow containing (8% NaCl), others were fed on high salt diet (8% NaCl) with interventions including Lisinopril 2.3mg/kg/d, Losartan 0.1mg/kg/d, Verapamil 0.1mg/kg/d, Vitamin C 100mg/kg/d, Magnesium 4.8mM and Kolaviron 200mg/kg/d. Drug administrations were by oral gavage. Blood pressure (mmHg) and heart rate (bpm) were monitored using the cufftail artery method. At the end of 8 weeks treatment period, animals were sacrificed using chloroform anaesthesia, carefully, the abdominal cavity was cut open by mid-line incision using a clean dissecting set. Left ventricle, aorta and mesenteric artery were harvested and blood samples were collected for platelet count, platelet indices and gene protein expression analyses. The result showed a significant increase in the mean arterial pressure, systolic and diastolic pressure in saltloaded rats compared with control, the high salt + Lisinopril, Losartan, Verapamil, Vitamin C, Magnesium and Kolaviron groups showed significant reduction in blood pressure compared with high salt group. There was a significant increase in platelet activating factor (PAF) gene expression in high salt group compared with control. High salt co-treated with Lisinopril, Losartan, Verapamil,
Vitamin C, Magnesium and Kolaviron groups showed significant decrease in PAF gene expression compared to high salt group. There were no significant changes in platelet count across groups compared with control. There was a significant decrease in mean platelet volume in HS +
Lisinopril and HS + Verapamil groups compared with control but there were no significant changes in all the other groups compared with control. There were no significant changes in plateletcrit in all the groups compared with control. There were no significant changes in platelet distribution width in all the groups compared with control. There was significant decrease in platelet large cell
ratio in HS + Lisinopril, HS + Verapamil and HS + Kolaviron groups compared with control but there were no significant changes in all the other groups compared with control respectively. In conclusion, this study provides evidence that suggests that high salt diet may alter platelets
function through oxidative, and protein enzyme receptor pathways which may be explored for improvement in therapeutic interventions.
Supervisor(s)
co-supervisor