DEPARTMENT OF PHYSIOLOGY

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

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

INVESTIGATION OF THE MECHANISM OF EFFECT OF ETHANOLIC EXTRACT OF BEETROOT ON THE LUNGS’ iNOS (INDUCIBLE NITRIC OXIDE SYNTHASE) AND NITRIC OXIDE LEVELS OF ADULT MALE WISTAR RATS EXPOSED TO HEAT AND BIOMASS SMOKE

Year of Publication
Publication Type
Abstract
Beetroot makes an excellent dietary supplement as it is not only rich in minerals, vitamins and nutrients but it also has unique Phytochemical compounds (carotenoids, phenolic acids, ascorbic acid) which have many medicinal uses. Heat is an environmental and occupational hazard. The effects of heat on human health are further exacerbated by environmental, socioeconomic, demographic, physiological and behavioural factors. Biomass fuel is any living or recently living plant or animal-based material that is burned by humans as fuels, such as dried animal dung, charcoal and grass. Nitric oxide (NO) is a gaseous molecule that has a central role in signalling pathways involved in numerous physiological processes such as vasodilation, neurotransmission, inflammation, apoptosis and tumour growth. Hence, the study was designed to investigate the mechanism of effect of ethanolic extract of Beetroot on the lungs’ iNOS and nitric oxide levels of adult male Wistar rats exposed to heat and biomass smoke. Forty-nine (49) adults male Wistar rats were randomly assigned into seven (7) groups of seven (7) rats per cage. Group A served as the control; group B were exposed to smoke only; group C were exposed to heat only; group D were exposed to smoke and heat; group E were exposed to smoke with Beetroot; group F were exposed to heat with Beetroot; group G were exposed to smoke, heat with Beetroot. At the end of the twenty–eight (28) days experimental period, the rats were sacrificed under chloroform anaesthesia. Lung tissues were collected in plain bottles with formol saline and taken to the laboratory for nitric oxide and inducible nitric oxide synthase assay.
Supervisor(s)
co-supervisor

AGE DETERMINED CHANGES IN GLOMERULAR FILTRATION RATE AMONG BLACK ETHNIC NORMOTENSIVE AND HYPERTENSIVE NIGERIANS: ACROSS SECTIONAL STUDY

Year of Publication
Publication Type
Abstract
Glomerular filtration rate (GFR) is the volume of non-protein plasma filtered by the glomeruli per unit of time (average of 125 ml/min/1.73 m2 of body surface area in adults). Age-related physiological changes influence GFR and results in age determined annual rate of Decline (ADARD) of about 1ml/minute/year. The GFR decline varies among populations due to genetic and environmental factors but the extent and pattern of this decline among ethnic black Nigerians had not been characterized. This study evaluated age-determined changes in GFR among adult black Nigerians and compared values in normotensive and hypertensive individuals by using measured creatinine clearance (mCrCl) and GFR estimating equations as Cockroft-Gault equation (CG), modification of diet in renal disease (MDRD) and National Kidney Foundation chronic kidney disease epidemiology collaboration(NKF CKD-EP!). Two hundred and seventy (270) apparently healthy volunteers (18-70 years), were recruited and arranged 30 per grouped (15 males and 15 females) for 9 age groups (18-24, 25-29, 30-34, 35-39, 40-44, 45-49, 50-60, 61-65, 66-70 years). Their age, gender, Pulse rates (PR), blood pressure and mean arterial pressure(MAP)were documented. Ten (10) milliliters (ml) of spot urine was obtained for assays of sodium ion and potassium ion by Ion selective electrode. Spectrophotometric methods were used for creatinine (Cr) and albumin (for calculation of mean urine albumin creatinine ratio, mUACR). Ante-cubital venipuncture was done for 10 ml of venous blood (2 ml anti-coagulated and 8ml coagulated for serum extraction). About 4 ml of serum was used for assays of serum Cr and CystatinC (ELISA). Subjects provided 12 hours timed urine for mCrCl in ml/min. The Mean ± Sem of the data were calculated on excel worksheet and further statistics as analysis of variance (ANOVA), Student’s t-Test, regression analysis and graphs were done with SPSS-29. The mean GFR in ml/min/1.73 m2 were; mCrCl (124.86 ± 5.09), CG (85.22 ± 1.69), NKF CKD-EP! Cr (82.95 ± 1.27), NKF CKD-EP! Cystatin C (72.90 ± 3.88), NKFCKD-EP! Cr-cystc (79.62 ± 2.64) and MDRD(93.44 ± 1.01). The ADARD in GFR (inml/min/yr) were significant (P<0.01) for; mCrCl 3.64, CG equation (0.7501), NKF CKD-EP!cr 2021 (0.4398) and MDRD (0.503). Twenty-one percent (21.1%) of the subjects were hypertensive (MAP>100) and 90.5% had mean Urine Albumin Creatinine ratio (mUACR) of 81.12 ± 3.58 (>30 mg/g). The annual rate of increase in UACR was 1.4457 mg/g (P<0.001). The GFR was significantly lower in hypertensive (P<0.05) while UACR was significantly higher in hypertensive (P<0.01). The ADARD in GFR was significant and associated with significant increase in UACR indicating a strong relationship between these CKD. Hypertension and increased mUACR reduced GFR significantly and increased ADARD in GFR. Early on-set of CKD manifested in this population as increase in mUACR before decrease in GFR occurred. Assessment of GFR must include UACR.
Supervisor(s)
co-supervisor

EFFECTS OF FUNCTIONAL EXERCISE ON CORTISOL LEVELS IN HEALTHY ADULT MALES

Year of Publication
Publication Type
Abstract
One well established measures of functional ability and quality of life is the ability to walk. The six-minute walk test (6MWT) is a simple, low-tech, safe and well established, self-paced assessment tool to quantify functional exercise capacity in adults. The test is self-paced, with standardized instructions and encouragement being given as patients walk as far as possible for about six minutes through a flat corridor. The final distance is recorded in meters. This study was aimed to investigate the effect of functional exercise on cortisol levels in healthy adult males at the University of Benin. Forty-five (45) healthy adult males aged 18-29 years were recruited for this study. A straight hallway was used at the University of Benin, Physiology Department. The hallway was measured using a measuring tape to mark out 30m and calibrated at intervals of 3m. Two small cones were placed at both ends on the 30m mark to indicate the turnaround points.The subjects' Body Mass Index (BMI) was calculated before the test. The pre and post-test vitals were measured and recorded. The Subjects walked back and forth the cones on the 30m hallway and the number of laps walked was counted, recorded and then multiplied by 60 meters to get the total number of meters walked. A 5ml syringe was used for blood collection from the subjects, after collection, the vacutainer tube (plain bottle) was used to collect, store and transport blood samples for laboratory testing. Cortisol levels were measured pre and post-test. The analysis was done at the chemical pathology laboratory of the University of Benin Teaching Hospital, Benin City. A CORTISOL ELISA TEST KIT was used for the assessment of the cortisol level test. The statistical analysis was done using Graph Pad Prism statistical package Version 8.1. The standard error of mean (SEM) was used in graphs to display the results.The dependent and independent variable means were compared using the student t-test. P<0.05 was accepted as significant. The results showed that there was no significant change in cortisol levels before and after the six minute walk test and there was a weak negative correlation between distance covered and blood cortisol level. Furthermore, individual stress response profiles, genetic and hormonal fluctuations can all affect how much cortisol an individual produces in response to various stressors. The cortisol response to exercises intensities are influenced by various factors such as age, gender, time of day and level of physical activity
Supervisor(s)
co-supervisor

DIFFERENTIAL EFFECTS OF ANTIHYPERTENSIVE DRUGS AND NANOSILVER ON BRAIN AND KIDNEY FUNCTIONS IN CHRONIC SALT-LOADED SPRAGUE DAWLEY RATS

Author(s)
Year of Publication
Publication Type
Abstract
High blood pressure is a mounting worldwide health crisis, and a diet consistently high in salt is a major contributor. Whereas, widespread use of silver nanoparticles (AgNPs) leads to bioaccumulation, with studies confirming their tendencies to induce toxicological effects in these same organs. The aim of this study was to compare the effects of some of the antihypertensive drugs, Amlodipine, Lisinopril, Ascorbic Acid, and Losartan, alongside Nanosilver on both the kidney and the brain function in rats fed a long-term high-salt diet. Sixty-four (64) male Sprague dawley rats where divided into 8 groups (8 rats per group). Group 1(control) was given normal rats chow and water, Group 2 received high salt diet containing 8% NaCl, Group 3 received Nano-sliver and normal feed, Group 4 received high salt diets and Nanosilver, Group 5, received Nanos liver and Amlodipine (1mg/kg body weight), Group 6 received high salt diet and Lisinopril (2.3mg/kg body weight/ day). Group 7 received high salt diet and Vitamin C (50mg/kg bw/ day). Group 8 received high salt diet and Losartan (10mg/kg bw/day) for 12 weeks. All the animals were allowed access to water ad libitum and drugs administered by oral gavage. The Neurobehavioral functions and cognitions were assessed using Open field apparatus for Novel object recognition test (NOR), Y-maze for spontaneous movement and elevated plus maze for anxiety levels. Statistical analysis was done using T- test Graph Pad Prism Version 10.2.2, with significance set at (P<0.05). At the end of the study, blood samples were collected for biochemical analysis for urea, creatinine, sodium, potassium and nitrogen ion. The results of the study demonstrated that while chronic high salt intake did not promote a significant long-term weight gain, it did not produce detectable in blood serum urea, creatinine, potassium and nitrogen ion. In conclusion, the present study showed no indication of dysfunction in the blood parameters examined. This gives confidence in the blood and renal safety profile.
Supervisor(s)
co-supervisor

HE EFFECT OF OVERNIGHT FASTING ON SOME INFLAMMATORY RATIOS AND SERUM BILIRUBIN CONCENTRATION AMONGST A POPULATION OF STUDENTS IN UNIBEN

upload
Publication Type
Abstract
Overnight fasting which is a form of Intermittent fasting (IF) is a dietary approach where individuals consume regular meals during specific intervals and then undergo extended periods with minimal or no energy intake for time periods that can range from 12hours to several days, on recurring basis which has same health benefits as overnight fasting. Inflammatory ratios, which are used in medical diagnostics are calculated by analyzing the level or ratios of certain blood markers, including neutrophils, fibrinogen, platelets and others, to assess the presence and severity of inflammation in the body.
Supervisor(s)
co-supervisor

THE EFFECTS OF NANOSILVER ON VASCULAR REACTIVITY AND ENDOTHELIAL FUNCTION ON ISOLATED RABBIT CAROTID ARTERY

Year of Publication
upload
Publication Type
Abstract
Nanoparticles (Nano particles) are defined as structures with a diameter less than 100 nm and novel physical and chemical properties that differ sharply from the macro forms. The medical use of nanosilver particles is growing mainly due to their antimicrobial properties. The impact of NSPs on the regulation of vascular tone (vasoconstriction/vasodilation), blood flow distribution, heartbeat, electric mechanisms, etc.; as well as their protective or adverse role in the development and progression of cardiovascular pathologies has not been properly understood. The aim of this present work was to determine the effect of nanosilver on vascular reactivity in isolated rabbit carotid artery.
Supervisor(s)
co-supervisor