Regulation of Adrenergic and Imidazole Preferring Receptors in the Rabbit

The studies reported in this thesis were designed to investigate the effects of chronic adrenoceptor drug treatment on central and peripheral alpha2-adrenoceptor number in the rabbit. In addition, functional studies were carried out using the central depressor response to clonidine injection and vascular pressor response to bolus doses of alpha-methylnoradrenaline injection to examine central and peripheral responses, respectively. The effects of chronic adrenergic drug treatment on alpha- and beta-adrenoceptor number were examined in rabbit forebrain and hindbrain membranes and were compared with the effects in the periphery (kidney membranes) where appropriate. Also changes in receptor number were then compared with functional changes. In preliminary experiments, it was observed that [3H]yohimbine and [3H] idazoxan which have been described as alpha2-adrenoceptor ligands bind to the tissues used in these studies with different characteristics. This observation led to detailed examination and characterization of these binding sites (chapter three). The displacement of these ligands from their binding sites by a range of adrenergic drugs was examined. It was found that [3H]yohimbine bound to alpha2-receptors while [3H]idazoxan in addition to binding at alph2-receptors bound principally to a non-adrenergic site. In chapter four, the effects of chronic treatment with the alpha2-adrenoceptor antagonists yohimbine and idazoxan on alpha2-adrenergic receptors were examined and compared with effects on the non-adrenergic site labelled by [3H] idazoxan. Functional changes occurring as a result of these treatments were also examined. Chronic yohimbine and idazoxan treatments significantly attenuated both vascular pressor responses to alpha-methylnoradrenaline bolus doses and the central depressor response to intracisternal clonidine. Yohimbine treatment significantly elevated [3H]yohimbine binding to both forebrain and hindbrain but reduced [3H]idazoxan binding to kidney membranes with no change in the brain. Idazoxan treatment significantly increased [3H] yohimbine binding to the forebrain and decreased [3H]idazoxan binding to the kidney. In chapter five, the effects of chronic amitriptyline treatment either alone or in combination with idazoxan or yohimbine on alpha2-adrenergic and non-adrenergic binding sites along with effects on beta-adrenoceptor number were studied. Increasing catecholamine concentrations in the brain indirectly by chronic amitriptyline administration, significantly reduced [3H]yohimbine binding to the hindbrain but not the forebram. [3H] Idazoxan binding sites were not significantly affected by this treatment. Neither treatment with amitriptyline alone nor when combined with alpha2-adrenoceptor antagonists had any significant effects on the number of [3H]dihydroalprenolol ([3H]DHA) binding sites. Chapter six examined the effects of direct infusion of catecholamines into the rabbit brain via intracerebroventricular infusion. Neither adrenaline nor noradrenaline had any significant effect on [3H]DHA or [3H]yohimbine binding sites although chronic adrenaline but not noradrenaline infusion significantly attenuated the depressor response to clonidine injection. Adrenaline infusion significantly reduced [3H]idazoxan binding to the right cerebrum. Chapter seven studied effects of chronic guanabenz infusion on both number and function of alpha2-adrenoceptors. Chronic infusion with the alpha2-adrenoceptor agonist guanabenz significantly reduced [3H] yohimbine binding to both forebrain and hindbrain although no changes in kidney membranes were observed, while the number of [3H]idazoxan binding site in the kidney but not the forebrain or hindbrain was significantly reduced. Both the depressor and pressor responses to clonidine and alpha-methylnoradrenaline respectively were significantly attenuated by this treatment. Chapter eight was aimed at bringing all the results in this thesis together, making comparisons, drawing conclusions and making proposals for future studies. In this thesis it was observed that agonists can cause down regulation and antagonists up-regulation of the [3H] yohimbine binding site. Finally, no changes in beta-adrenoceptor number were observed in the rabbit brain during either catecholamine or amitriptyline treatments. This contrasts with observations in rat brain and reports of changes in beta-adrenoceptor number during catecholamine infusion into the periphery of rabbits. Small subtype changes may have occurred which were not detected, or alternatively, beta-adrenoceptors in rabbit brain are relatively resistant to down-regulation

In silico analysis of beta-lactoglobulin gene in some selected mammalian species

This study investigated in silico, the genetic diversity of Beta- Lactoglobulin (β-Lg) and their evolutionary and differentiation within and among selected mammalian species; and also examined the attendant effects of polymorphism on the functionality of the gene. A total of 21 β-Lg gene sequences with corresponding amino acids belonging to 6 species [cattle (4), buffalo (4), sheep (3), goat (3), pig (3) and horse (4)] were retrieved from GenBank (www.ncbi.nlm.nih.gov). All sequences were trimmed to equal length (500bp) corresponding to the same region. Sequences' alignment, translation and comparison were done with ClustalW using IUB substitution matrix, gap open penalty of 15 and gap extension penalty of 6.66. The alignment revealed high polymorphism of sequences among extant species. The Dxy inferred using p- distance revealed that sheep and goat had the lowest distance of 0.05 with a maximum distance of 0.65 between goat and horse. The hypothesis of strict neutrality (dN = dS ) was rejected for all extant species as allelic sequence evolution was driven by both purifying and positive selection. Only those of pig and buffalo were driven by positive selection. In-silico functional analysis of non-synonymous mutations using PANTHER revealed that, all the 12 amino acid substitutions (10 in cattle and 2 in sheep) did not impair protein function. The Neighbour-Joining phylogeny revealed trans-species evolution, but a species-wise phylogeny was obtained for UPGMA with consensus sequences. Thus, all probed SNPs from this study have no deleterious effect and can be tolerated by breeders when selecting stocks for milk improvement

Original Contribution RELATIONSHIP BETWEEN SOME BODY MEASUREMENTS AND LIVE WEIGHT IN ADULT MUSCOVY DUCKS USING PATH ANALYSIS

ABSTRACT Weight and body dimensions (body length (BL), chest circumference (CC), thigh length (TL), shank length (SL) and neck length (NL) were studied using 215 fifteen weeks male and female Nigerian indigenous Muscovy ducks by path analysis. The result showed that the correlation coefficient between live weight and body dimensions on the other hand were 0.89, .94, .87, .88 and .75 (male) and .29, .59, .41, .37, -.10 (female) for BL, CC, TL, SL and NL respectively. The direct effect of chest circumference was higher in both male and female (0.616, .571) with the neck length having the least and negative direct effects on weight for both sexes. Indirect effect of body length through chest circumference was also the highest .chest circumference is the most influential variable and can be included in the model in estimating live weight of both male and female Muscovy duck at 15 weeks of age

Cardioprotective effects and antioxidant status of Andrographis paniculata in isoproterenol-induced myocardial infarction in rats

Background: Myocardial infarction has been regarded as one of the fastest killer diseases of modern-day man. Aim: The protective effect of Andrographis paniculata on isoproterenol (ISO)-induced myocardial infarction in rats was investigated. Setting: The study was carried out in a laboratory setting. Methods: Animals were randomly divided into six groups of seven animals per group, and the treatment was as follows: normal control received normal saline for 9 days, isoproterenol group; three extract-treated groups in pre-treatment phase and an extract-treated group in post-treatment phase. The doses were given at 100, 200 and 400 mg/kg body weight for pre-treatment phase respectively while 200 mg/kg dose was given to the post-treatment phase group. Blood and heart tissues were collected for biochemical assays, haematological and histological analyses. Results: Myocardial infarction was recorded in ISO group but was corrected by the extracts in both pre-treatment and post-treatment phases. The ISO group experienced a significant decrease in antioxidant parameters, whereas the extract at all doses caused a significant increase in the activities of in these parameters. The extract caused a significant decrease in malondialdehyde content and hydrogen peroxide generation, whereas reverse was the case for the ISO group. Although no significant histopathological changes were recorded for the extract, the ISO group showed marked histopathological changes. ISO caused higher expressions of cardiac C-reactive protein (CRP) and CTnI and decreased the expressions of IL-10β; but this was the opposite for the extract. Conclusion: The ethanol leaf extract of A. paniculata significantly exhibits cardioprotective effects

An overview of anti-diabetic plants used in Gabon: Pharmacology and Toxicology

© 2017 Elsevier B.V. All rights reserved.Ethnopharmacological relevance: The management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed. Materials and methods: Ethnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including ‘Diabetes’ ‘Gabon’ ‘Toxicity’ ‘Constituents’ ‘hyperglycaemia’ were used. Results: A total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver. Conclusion: An in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon.Peer reviewedFinal Accepted Versio

The therapeutic potential of the novel angiotensin-converting enzyme 2 in the treatment of coronavirus disease-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). This virus has become a global pandemic with unprecedented mortality and morbidity along with attendant financial and economic crises. Furthermore, COVID-19 can easily be transmitted regardless of religion, race, sex, or status. Globally, high hospitalization rates of COVID-19 patients have been reported, and billions of dollars have been spent to contain the pandemic. Angiotensin-converting enzyme (ACE) 2 is a receptor of SARS-CoV-2, which has a significant role in the entry of the virus into the host cell. ACE2 is highly expressed in the type II alveolar cells of the lungs, upper esophagus, stratified epithelial cells, and other tissues in the body. The diminished expressions of ACE2 have been associated with hypertension, arteriosclerosis, heart failure, chronic kidney disease, and immune system dysregulation. Overall, the potential drug candidates that could serve as ACE2 activators or enhance the expression of ACE2 in a disease state, such as COVID-19, hold considerable promise in mitigating the COVID-19 pandemic. This study reviews the therapeutic potential and pharmacological benefits of the novel ACE2 in the management of COVID-19 using search engines, such as Google, Scopus, PubMed, and PubMed Central.http://www.veterinaryworld.orgdm2022Paraclinical Science

Clofibrate, a peroxisome proliferator–activated receptor-alpha (PPARα) agonist, and Its molecular mechanisms of action against sodium fluoride–induced toxicity

AVAILABILITY OF DATA AND MATERIALS : Data will be made available based on request from the corresponding author.Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator–activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride.Cape Peninsula University of Technology and National Research Foundation (South Africa).https://link.springer.com/journal/12011hj2023Paraclinical Science

The methanol seed extract of Garcinia kola attenuated angiotensin II- and lipopolyssacharide-inducedvascular smooth muscle cell proliferation and nitric oxide production

All over the world, cardiovascular diseases are a risk factor for poor health and early death with predisposing factors to include age, gender, tobacco use, physical inactivity, excessive alcohol consumption, unhealthy diet, obesity, family history of cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, psychosocial factors, poverty and low educational status, and air pollution. It is envisaged that herbal products that can stem this trend would be of great benefit. Garcinia kola (GK), also known as bitter kola is one of such plants. Generally used as a social snack and offered to guests in some cultural settings, bitter kola has been indicated in the treatment of laryngitis, general inflammation, bronchitis, viral infections and diabetes. In this study, the effects of methanol seed extract of Garcinia kola on the proliferation of Vascular Smooth Muscle Cells (VSMCs) in cell culture by Angiotensin II (Ang II) and LPS-induced NO production were carried out. Confluent VSMCs were exposed to GK (25, 50 and 100 μg/ml) before or after treatment with lipopolyssacharide (100μg/ml), and Angiotensin II (10-8-10-6M). Cellular proliferation was determined by MTT assay and NO production by Griess assay. Treatment with Angiotensin II (10-8, 10-6) or LPS significantly enhanced proliferation of VSM cells while LPS significantly increased nitric oxide (NO) production. Treatment with GK (25, 50 & 100 μg/ml) attenuated VSM cell proliferation. The results indicate that GK has potential to inhibit mitogen activated vascular cell growth and possibly inhibit inflammatory responses to LPS. Thus GK may be useful in condition that is characterized by cellular proliferation and inflammatory responses

Oxidative stress indices in ASD children in Sub-Sahara Africa

Background: The pathogenesis of autism spectrum disorder (ASD) remains a medical challenge even in the developed world. Although genetics and epigenetic factors have been variously indicted as major causes of the disorder, development of oxidative stress especially in the formative years of children has equally gained prominence as an etiological basis of the disorder. Oxidative stress is characterized by the production of excessive amounts of free radicals, decreased levels of antioxidants with the attendant imbalance in oxidant/antioxidant ratio. This study was designed to determine the levels of essential metals [magnesium (Mg), zinc (Zn), and copper (Cu)] and toxic metal, lead (Pb), and generation of oxidative stress by their abnormal interaction. Method: Twenty-five children clinically diagnosed for ASD according to DSM-IV-TR and 25 neuro-typical (NT) children (controls), (aged 5.96 ± 1.40 years and 6.18 ± 2.59 years respectively) were recruited for this study. Essential and toxic metals were analyzed using induction-coupled plasma-mass spectrometry (ICP-MS); oxidative stress markers [malondialdehyde (MDA), total plasma peroxidase (TPP), and total antioxidant capacity (TAC)] were determined using appropriate biochemical methods. Oxidative stress index (OSI) was calculated. Results: The levels of TPP and TAC were significantly reduced while MDA was higher in ASD compared to NT. Although OSI was higher in ASD, the difference was not significant. Pb (lead) concentration was significantly increased while Mg, Zn, and Cu levels were reduced significantly in ASD compared to NT. A significant negative correlation between Mg and OSI (r = − 0.438; p = 0.029) was observed in NT. Conclusion: Reduction in Zn and Mg levels with a concurrent increase in Pb in children with ASD in this study may be the basis of inadequate TAC manifesting as increased MDA and reduced TPP levels. The attendant imbalance in oxidant/antioxidant ratio may result in abnormality in neuronal transduction leading to the abnormal cognitive and speech functions characteristic of ASD