26 research outputs found
Body temperature and physical activity correlates of the menstrual cycle in female chacma baboons (Papio hamadryas ursinus)
MSc (Med), Faculty of Health Sciences, University of the WitwatersrandI investigated the relationship between abdominal temperature, physical activity, anogenital swellings, and faecal and urine ovarian steroid hormonal concentrations over the menstrual cycle in baboons in an attempt to devise a reliable non-hormonal physiological indicator to detect ovulation. Using a miniature thermometric data logger surgically implanted in the abdominal cavity and an activity data logger implanted subcutaneously on the trunk, I measured, continuously over six months at a 10 min interval, abdominal temperature and physical activity patterns in four female adult baboons, Papio hamadryas ursinus (12.9-19.9 kg), unrestrained in cages in an indoor animal facility (22-25°C). I monitored menstrual bleeding, and anogenital swelling changes using digital photography, and collected urine and faeces, daily, to ascertain the stage and length of the menstrual cycle. The length of the menstrual cycle, determined from daily observations of menstrual bleeding and anogenital swellings, was 36 ± 2 days (mean ± SD). Baboons exhibited a cyclic change in anogenital swellings, abdominal temperature, physical activity, urine and faecal steroid hormones over the menstrual cycle. Mean 24-h abdominal temperature during the luteal phase was significantly higher (ANOVA, p = 0.04; F (2,9) = 4.7) than during the ovulatory phase, but not different to the follicular phase. Physical activity also followed a similar pattern, with mean 24 h physical activity almost twice as high in the luteal than in the ovulatory phase (ANOVA, p = 0.58; F (2,12) = 5.8). As expected, urine and faecal oestradiol was higher in the follicular than in the luteal phase, while progesterone was higher in the luteal than the follicular phase. Cortisol in both urine and faecal samples did not show any
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recognisable menstrual cycle related pattern. I have characterised correlates of the menstrual cycle in baboons and shown, for the first time, a rhythm of physical activity over the baboon menstrual cycle. I have also shown, from the measurements of abdominal temperature, physical activity, ovarian steroid hormonal concentrations and anogenital swellings, that ovulation in captive unrestrained baboons, and probably also free-living baboons, can be estimated from anogenital swellings or possibly abdominal temperature and physical activity, without the need for hormone measurements
The effect of neonatal administration of oleanolic acid on health outcomes associated with diet-induced metabolic dysfunction in rats
A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, School of Physiology, fulfilment of the requirements for the degree of Doctor of Philosophy (PhD).
Johannesburg, South Africa, 2018.The neonatal period is a critical window of developmental plasticity. Consumption of fructose-rich diets has been implicated in the increasing global prevalence of metabolic dysfunction (MD) and non-alcoholic liver disease (NAFLD). Interventions during periods of early ontogenic developmental plasticity can induce epigenetic changes which program metabolism for positive health benefits later in life. The phytochemical, oleanolic acid (OA) possesses anti-diabetic, anti-oxidant and anti-obesity effects. I investigated the potential protective effects of neonatal oral administration of OA on the subsequent development of health outcomes associated with fructose-induced MD and NAFLD in male and female rats.
The study was divided into two major experiments. In the first short-term experimental study, the potential of neonatal oral administration of OA to acutely protect against the development of fructose-induced oxidative damage, adverse general health outcomes and precocious maturation of the gastrointestinal tract (GIT) in suckling male and female rats was investigated. Male and female suckling rat pups (N=30) were randomly assigned to four groups and gavaged daily with 10 mℓ/kg body mass of: distilled water (DW) with 0.5% (v/v) dimethyl sulphoxide (vehicle control), oleanolic acid (OA; 60 mg/kg), high fructose solution (HF; 20% w/v), or OAHF for 7 days. On day 14, the pups were euthanised. Blood, liver and skeletal muscle samples were collected to determine clinical health profiles, hepatic lipid content and gene expression of anti-oxidant enzymes, superoxide dismutase (SOD2) and glutathione peroxidase (GPx1). Rats in all groups had a significant increase in body mass over the seven day treatment period (ANOVA; P0.05). Neonatal oral administration of fructose lowered the expression of genes for anti-oxidant enzymes (SOD2 and GPx1) which was prevented by OA (ANOVA; P<0.05). Findings from this study provide evidence that short-term neonatal oral administration of OA protects against fructose-induced oxidative damage with seemingly no adverse effects on health or the maturational and developmental changes of the gastrointestinal tract in suckling male and female pups.
In the second long-term experimental study, which was further subdivided into two studies, I investigated the potential protective effects of neonatal oral administration of OA on the
subsequent development of high fructose diet-induced a) metabolic dysfunction and b) NAFLD in male and female rats. Male and female suckling rats (N=112) were randomly assigned into four groups and gavaged daily with 10 m mℓ/kg body mass of: distilled water (DW) with 0.5% (v/v) dimethyl sulphoxide (vehicle control), oleanolic acid (OA; 60 mg/kg), high-fructose solution (HF; 20% w/v) and OAHF for 7 days. On day 21, the rats were weaned onto normal rat chow and plain drinking water up to day 55. From day 56, half of the rats in each treatment group were continued on plain water whilst the remainder were given a high fructose solution (20 % w/v) as drinking fluid ad libitum for eight weeks. On day 110 the rats were subjected to an oral glucose tolerance test (OGTT) and then euthanised on day 112. Fasting glucose, triglyceride levels and terminal body mass were measured before termination. Blood samples were collected to determine the effects of treatments on fasting levels of cholesterol, insulin, glucose, triglycerides, insulin resistance (HOMA-IR), glucose tolerance (area under the curve for OGTT), a surrogate biomarker of liver function, alanine amino transaminase (ALT) and non-tissue specific alkaline phosphatase (ALP). Body adiposity was determined by measuring visceral and epidydimal fat pad masses. Liver samples were used to measure hepatic lipid accumulation and hepatic histomorphometry. The livers were formalin fixed, paraffin embedded and sectioned at 3μm. The sections were stained with haematoxylin and eosin for assessment of inflammation and Masson’s trichrome for visualisation of connective tissue and steatosis.
Male and female rats in all groups of the second experiment had a significant increase in body mass over the study period (ANOVA; P0.05).
The sub-study on NAFLD revealed that fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47-49% increase in hepatic lipid content of both
male and female rats (P˂0.05). However, fructose administered in adulthood only (DW+F), caused a significant increase in liver lipid content in females only (P0.05). NAFLD area fraction for fibrosis was 3 times higher in male and female rats that received a double hit neonatally and in adulthood (HF+F) and a late hit of fructose (DW+F) compared to the rats in the negative control group (P<0.05).
I have shown that administration of a high fructose diet had adverse effects on several health outcomes associated with MD and induced NAFLD. However, it was notable that the timing of the fructose intake in the life stage of rats had an impact on the development of MD and NAFLD phenotype. I also observed sex-specific differences in the metabolic response to dietary fructose, with females appearing to be more vulnerable to the development of MD and NAFLD. It is thus important to note that studies should not just focus on a single sex but should be comparative between the sexes. I have also demonstrated, for the first time, that neonatal oral administration of oleanolic acid protects against the subsequent development of fructose-induced health outcomes associated with metabolic dysfunction and NAFLD by reducing hepatic lipid storage, terminal liver masses and hepatic histomorphological changes associated with NAFLD. I conclude that neonatal interventional treatment with oleanolic acid during the critical window of developmental plasticity protected against the development of fructose diet-induced adverse health outcomes associated with MD and NAFLD in male and female Sprague Dawley rats. Therefore, OA is a phytochemical that exhibits potential in the prevention of neonatal programming of MD and NAFLD later in life. OA should be considered as a natural strategic prophylactic intervention during periods of developmental plasticity with a lot of potential in the fight against the scourge of metabolic disorders that have a significant negative impact on the health systems globally.LG201
A study on neonatal intake of oleanolic acid and metformin in rats (rattus norvegicus) with metabolic dysfunction : implications on lipid metabolism and glucose transport
Abstract: Metabolic syndrome, a cluster of different disorders which include diabetes, obesity and cardiovascular diseases, is a global epidemic that is growing at an alarming rate. The origins of disease can be traced back to early developmental stages of life. This has increased mortalities and continues to reduce life expectancies of individuals across the globe. The aim of this study was to investigate the sub-acute and long term effects of neonatal oral administration of oleanolic acid and metformin on lipids (free fatty acids, FFAs) and genes associated with lipid metabolism and glucose transport using a neonatal rat experimental model. In the first study, seven days old pups were randomly grouped into control—distilled water (DW); oleanolic acid (60 mg/kg), metformin (500 mg/kg), high fructose diet (20% w/v, HF), oleanolic acid (OA) + high fructose diet (OA + HF), and Metformin + high fructose diet (MET + HF) groups. The pups were treated for 7 days, and then terminated on postnatal day (PD) 14. In the second study, rat pups were initially treated similarly to study 1 and weaned onto normal rat chow and plain drinking water on PD 21 till they reached adulthood (PD112). Tissue and blood samples were collected for further analyses..
Early postnatal administration of oleanolic acid attenuates the development of non- alcoholic fatty liver disease in fructose fed adult female rats
Abstract: Please refer to full text to view abstrac
Ficus thonningii stem bark extracts prevent high fructose diet induced increased plasma triglyceride concentration, hepatic steatosis and inflammation in growing Sprague-Dawley rats
BACKGROUND : Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activitiese investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against high-fructose diet-induced Metabolic Derangements (MD) in a model mimicking childreenic diets.
METHODS : Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocated to and administered, for 8 weeks, five treatment regimens: 1-standard rat chow (SC)+water (PW), 2-SC+20% (w/v) fructose solution (FS), 3-SC+FS+fenofibrate at 100 mg/kg bwt/ day, 4-SC+FS+low dose MEFT (LD; 50 mg/kg bwt/day) and 5-SC+FS+high dose MEFT (HD; 500 mg/kg bwt/ day). Body weight, glucose load tolerance, fasting blood glucose and triglyceride, plasma insulin concentration, sensitivity to insulin, liver mass and fat content, steatosis and inflammation were determined.
RESULTS : Fructose had no effect on the rats’ growth, glucose and insulin concentration, glucose tolerance and insulin sensitivity (P>0.05) but increased triglycerides in females; induced hepatic microsteatosis and inflammation in both sexes but macrosteatosis in females (P<0.05). In females, MEFT prevented fructose- induced plasma triglyceride increase. Low dose MEFT increased liver lipid content in females (P<0.05). The MEFT protected the rats against hepatic steatosis and inflammation but fenofibrate protected against hepatic microsteatosis.
CONCLUSION : MEFT can d as prxis against dietary fructose-induced elements of MD but caution musaken as low dose MEFT increases hepatic lipid acc in females predisposing to fatty liver disease.The National Research Foundation, South Africa and Wits University Faculty of Health Sciences Research Committee.https://www.sysrevpharm.org/about.htmlhj2022Physiolog
Long-Term Impact of Neonatal Intake of Oleanolic Acid on the Expression of AMP-Activated Protein Kinase, Adiponectin and Inflammatory Cytokines in Rats Fed with a High Fructose Diet
Abstract: AMP-activated protein kinase (AMPK) is known to regulate both glucose and lipid metabolism, which play vital roles in the development of metabolic syndrome. One way of regulating AMPK is through hormonal activation using adiponectin. Patients diagnosed with type-2 diabetes (T2D) and obesity exhibit low adiponectin concentration levels in their blood. Moreover, studies have also shown that inflammatory processes play a significant role in the etiology of these metabolic diseases. In this study, the long-term effects of neonatal intake of oleanolic acid (OA) on the AMPK gene, genes associated with glucose transport and lipid metabolism, adiponectin levels, and inflammatory biomarkers in rats fed with a high fructose diet were investigated. Seven day old pups were randomly divided into five groups and treated as follows; 0.5% dimethylsulphoxide v/v in distilled water vehicle control (CON), oleanolic acid (OA, 60 mg/kg), high fructose diet (HF, 20% w/v), high fructose diet combined with oleanolic acid (HF+OA), and high fructose diet combined with metformin (HF+MET, 500 mg/kg)..
Early‐life exposure to alcohol and the risk of alcohol‐induced liver disease in adulthood
Alcohol consumption remains prevalent among pregnant and nursing mothers despite the well‐documented adverse effects this may have on the offspring. Moderate‐to‐high levels of alcohol consumption in pregnancy result in fetal alcohol syndrome (FAS) disorders, with brain defects being chief among the abnormalities. Recent findings indicate that while light‐to‐moderate levels may not cause FAS, it may contribute to epigenetic changes that make the offspring prone to adverse health outcomes including metabolic disorders and an increased propensity in the adolescent‐onset of drinking alcohol. On the one hand, prenatal alcohol exposure (PAE) causes epigenetic changes that affect lipid and glucose transcript regulating genes resulting in metabolic abnormalities. On the other hand, it can program offspring for increased alcohol intake, enhance its palatability, and increase acceptance of alcohol's flavor through associative learning, making alcohol a plausible second hit for the development of alcohol‐induced liver disease. Adolescent drinking results in alcohol dependence and abuse in adulthood. Adolescent drinking results in alcohol dependence and abuse in adulthood. Alterations on the opioid system, particularly, the mu‐opioid system, has been implicated in the mechanism that induces increased alcohol consumption and acceptance. This review proposes a mechanism that links PAE to the development of alcoholism and eventually to alcoholic liver disease (ALD), which results from prolonged alcohol consumption. While PAE may not lead to ALD development in childhood, there are chances that it may lead to ALD in adulthood.Thuthuka granthttp://wileyonlinelibrary.com/journal/bdr2hj2021Physiolog
Orally administered zingerone does not mitigate alcohol-induced hepatic oxidative stress in growing Sprague Dawley rat pups
DATA AVAILABILITY STATEMENT : Researchers may request data from the authors. Additional data is provided.Neonatal alcohol exposure (NAE) can induce oxidative stress. We determined whether zingerone (ZO), a phytochemical with anti-oxidant activity, can mitigate the negative impact of neonatal alcohol-induced oxidative stress. Seventy ten-day-old Sprague-Dawley rat pups (35 male, 35 female) were randomly assigned and administered the following treatment regimens daily from postnatal day (PND) 12–21: group 1 – nutritive milk (NM), group 2 – NM +1 g/kg ethanol (Eth), group 3 – NM + 40 mg/kg ZO, group 4 – NM + Eth + ZO. Growth performance, blood glucose and plasma triglycerides (TGs), total cholesterol, HDL-cholesterol, leptin and insulin concentration were determined. Cytochrome p450E21(CYP2E1) and thiobarbituric acid (TBARS); markers of hepatic oxidative stress and catalase, superoxide dismutase (SOD) and total glutathione (GSH), anti-oxidant markers of the pups were determined. Oral administration of ethanol (NM + Eth), zingerone (NM + ZO) and combined ethanol and zingerone (NM + Eth + ZO) did not affect the growth performance and insulin and leptin concentration of the rats (p > 0.05). Ethanol significantly reduced plasma TGs concentration of female rats (p = 0.04 vs control). However, ethanol and/or its combination with zingerone decreased hepatic GSH (p = 0.02 vs control) and increased CYP2E1 (p = 0.0002 vs control) activity in male rat pups. Zingerone had no effect (p > 0.05 vs control) on the rats' CYP2E1, GSH, SOD and catalase activities. Neonatal alcohol administration elicited hepatic oxidative stress in male rat pups only, showing sexual dimorphism. Zingerone (NM + ZO) prevented an increase in CYP2E1 activity and a decrease in GSH concentration but did not prevent the alcohol-induced hepatic oxidative stress in the male rat pups.The National Research Foundation (NRF) Thuthuka Fund and the Faculty of Health Sciences Research Committee Grant.https://www.tandfonline.com/journals/idct20hj2023Physiolog
Proximate content and lipid profile of seeds from rapanea melanophloeos (the Cape beech) tree
Abstract: Rapanea melanophloeos (Cape beech) is a fruit-bearing tree indigenous to Southern Africa which produces edible fruit. Previous studies have focussed on investigating the nutritional potential of the tree’s fruit pulp. The nutritional potential of R. melanophloeos seeds is unknown. Seed samples obtained from ripe fruit of the Cape beech trees had their proximate analysis and lipid profiling done. The dry matter and ash contributed 91.29 ± 0.00 %, 1.50 ± 0.01 % of the mass of the seed. Whilst the other proximate analytes namely crude fibre, crude protein and ether extract made up 5.71 ± 0.43 % , 10.50 ± 0.49 % and 4.75 ± 0.09 % the mass of the seeds respectively. The fatty acid profile of the seed oil revealed Linoleic acid (50.43 ± 0.38 %) to be the most dominant. R. melanophloeos seeds are not a viable source of nutrients
An overview of the potential use of ethno-medicinal plants targeting the Renin–Angiotensin system in the treatment of hypertension
The development of risk factors associated with cardiovascular disorders present a major
public health challenge in both developed countries and countries with emerging economies.
Hypertension and associated complications including stroke and myocardial infarction have
reached pandemic levels. Current management strategies of hypertension predominantly include
the utilization of pharmaceutical drugs which are often associated with undesirable side e ects.
Moreover, the drugs are often too expensive for populations from resource-limited Southern African
rural, and some urban, communities. As a result, most patients rely on ethno-medicinal plants for the
treatment of a variety of diseases including cardiovascular and metabolic disorders. The e ectiveness
of these plants in managing several cardiovascular diseases has been attributed to the presence
of bioactive phytochemical constituents. In this review, the treatment options that target the
renin–angiotensin system (RAS) in the management of hypertension were summarized, with special
emphasis on ethno-medicinal plants and their influence on the ACE1 RAS pathway. The dearth of
knowledge regarding the e ect of ethno-medicinal plants on the ACE2 pathway was also highlighted.http://www.mdpi.com/journal/moleculesam2021Physiolog