School of Physiology (ETDs)

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    Isolated nocturnal hypertension and target organ damage in a population of African descent
    (University of the Witwatersrand, Johannesburg, 2024) Phukubje, Edgar Matome; Maseko, Muzi
    The use of ambulatory blood pressure monitoring (ABPM) has revolutionised the approach to hypertension diagnosis and management. The ability to monitor blood pressure over a 24-hour period has enabled researchers to monitor blood pressure profile away from the doctor’s clinic, which has led to the diagnosis of various hypertension phenotypes like masked hypertension, isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH), and others. Previous studies have shown that night-time blood pressure is more closely related to target organ damage compared to daytime blood pressure. Since more studies indicate that people of African ancestry have elevated night-time blood pressure compared to other population groups, nocturnal blood pressure monitoring in this population group is crucial. However, there are few studies that have investigated the prevalence of INH, and their results are inconclusive. Hence the impact of INH on cardiovascular target organ damage is not well understood in this population group. It has been reported that dietary salt intake (DSI) has more severe cardiovascular outcomes in African populations compared to non-African populations groups because they are said to be salt sensitive. However, there are no studies that have investigated the relationship between 24-hour urinary salt excretion and 24-hour dipping patterns in populations of African ancestry. In addition, the impact of INH on target organ damage has never been compared to that of IDH. Hence, current intervention strategies primarily rely on daytime blood pressure to diagnose and treat hypertension. The relationship between age and blood pressure is well understood, but current studies have mainly focused on daytime blood pressure. The impact of age on nocturnal blood pressure is not well understood in this population group, and it is also unclear whether the age-related changes in nocturnal blood pressure translate to any cardiovascular target organ changes. Therefore, the aim of this study was to determine the relationship between INH and cardiovascular target organ damage in a South African population of African ancestry. A total 1600 participants above 18 years were recruited. These form part of the ongoing South African Hypertension and Diet Study in the Human Nutrition Research Laboratory. Office blood pressure was measured conventionally and through SpaceLabs ambulatory oscillometric monitors for 24-hours. Target organ function was determined through echocardiographic measurements and applanation tonometry using the sphygmocor device. 24-hour urine samples were collected to determine electrolyte excretion rates. Blood was collected when the participants visited the clinic. Only data with complete 24-hour ABPM matched with complete urinary collections were included for data analysis and the final sample was 796 participants. v Findings from the current study showed that 11% of the participants had INH, 13% had 24- hour sustained hypertension and 4% had IDH. The three groups had different dipping patterns. The sustained hypertensive group were non-dippers, IDH group were dippers, and the INH group had two dipping patterns: non-dipping (IND) and reverse dipping (IRD). Urinary electrolyte concentrations were significantly higher in IDH, and lower in INH. The INH group and 24-hour sustained hypertensives were the oldest cohort, while the NT and IDH were youngest. Pulse wave velocity (PWV) was significantly higher in the IND and IRD. The NT and IDH group had the lowest PWV. PWV in the INH was similar but not significantly different to the 24-hour sustained HT group. These findings indicate that the two INH subtypes (IND and IRD) damage large arteries to a similar effect as 24-hour sustained hypertension, while IDH does not cause any damage. The ABPM results were used to show changes in blood pressure with age. Different age group ranges were used, in increments of 10 years. Increased nocturnal blood pressure was associated with being older. Additionally, age-related changes in nocturnal blood pressure were associated with pre-clinical diastolic dysfunction. The current findings further show that blood pressure related cardiovascular target organ damage occurs during night-time in this population group. Urine analysis showed increased excretion in IDH and sodium retention in INH. Aldosterone levels were significantly higher in the INH, compared to 24-hour sustained HT group. Low aldosterone and salt retention increased nocturnal BP in the INH group. This means the current rise in the prevalence of cardiovascular disease in people of African descent despite increased efforts to diagnose and treat hypertension, is driven by INH, which remains undiagnosed because of the over reliance on conventional blood pressure measurement
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    Is 24-hour augmentation index a better indicator of arterial stiffness compared to clinic augmentation index?
    (University of the Witwatersrand, Johannesburg, 2024) Mukhovha, Wantonda Papinah; Maseko, Muzi
    Arterial Stiffness is a major independent risk factor that is strongly associated with an increased risk of developing cardiovascular diseases (CVDs), making it an important marker in the assessment of CVD risk. Therefore, in an effort to reduce the rising incidence of cardiovascular diseases in South Africa, it is crucial to determine the best indicator for arterial stiffness. Currently two indices are used to measure arterial stiffness, pulse wave velocity (PWV) and augmentation index (AI). Since arterial stiffness measurement techniques were developed much later than blood pressure (BP) measurement techniques, important lessons can be learned from BP measurement. Studies have indicated that 24-hour BP measurement is a much better tool of measurement compared to a once off conventional BP measurement. This creates a possibility that 24-hour arterial stiffness assessment is a better tool for measuring arterial stiffness compared to a once off clinic arterial stiffness measurement. Therefore, in this study we compared 24-hour AI to in-clinic AI and also assessed gender differences. Previous studies conducted on 24-hour AI were focused on establishing normal 24-hour AI reference values. To date, no studies have been conducted to compare 24-hour AI to in-clinic AI. Moreover, gender differences in the 24-hour arterial stiffness profile have never been studied. We recruited 125 individuals of black African descent and took anthropometric measurements. We measured both conventional BP and 24-hour BP. Pulse wave analysis was performed to obtain both in-clinic and 24-hour AI. In the total population, 24-hour augmentation index (AI24) was significantly higher than in-clinic augmentation index (AIC) (p<0.0001). When participants were stratified according to gender, AI24 was significantly higher than AIC in both men (p<0.0001) and women (p<0.0001). Night-time augmentation index (AIN) in the total population was significantly higher than daytime augmentation index (AID) (p=0.0143). When participants were stratified according to gender, our results show that AIN was only significantly higher in women (p=0.0291) and not in men. Our results show that AIC may grossly be underestimating the prevalence of arterial stiffness and its adverse effects on cardiovascular target organs. Secondly, our results also show that there are gender differences in arterial stiffness fluctuations over the 24-hour period. In men, daytime arterial stiffness does not differ from night-time arterial stiffness. However, in women arteries become stiffer during the night-time compared to the daytime. These findings indicate that special attention must be given to night-time arterial stiffness because it may be more closely related to target organ damage than daytime arterial stiffness.
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    The association between poor sleep quality and cardiometabolic risk in HIV+ individuals and the general population living in a rural area of South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Reddy, Tracy; Scheuermaier, Karine; Karstaedt, Alan
    Studies show that both poor sleep quality and HIV infection independently increase cardiometabolic risk (CMR). Additionally, poor sleep quality is common with HIV infection. Our study investigated whether HIV infection interacts with poor sleep quality to affect CMR in people living with HIV (PLWH) in a rural area of South Africa. We recruited 200 HIV+ participants and 200 controls from Qwa Qwa in Free State in South Africa and assessed their CMR, sleep quality, daytime sleepiness, risk of obstructive sleep apnoea and degree of depressive symptoms. Sleep quality (p = 0.15), daytime sleepiness (p = 0.31) and the cardiometabolic risk score (MetScore) (p = 0.93) were similar between HIV+ and control participants. Fewer HIV+ participants had a high risk of sleep apnoea (p = 0.019) but more HIV+ participants had symptoms of clinical depression (p = 0.0007). Poorer sleep quality in the HIV+ participants was associated with pain (p = 0.0006), more severe depressive symptoms (p<0.0001) and longer HIV duration (p = 0.011). However, HIV infection was not associated with a higher MetScore (p = 0.18) once age, sex and sleep and depression markers were adjusted for. Additionally, HIV infection increased the risk of hypertension (p = 0.016). HIV status did not interact with sleep quality (p = 0.32) to affect CMR. Our findings indicate that healthcare facilities should consider monitoring CMR factors in HIV+ individuals.
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    Comparison of Aortic Haemodynamics in Community Participants and Patients with Systolic Heart Failure and the Impact of Blood Pressure Control
    (University of the Witwatersrand, Johannesburg, 2024) Lebelo, Ntapo Marcus
    In patients with systolic heart failure (HF), both decreases and increases in pulse pressure (PP) are associated with poor prognosis. If aortic PP in systolic HF is decreased due to systolic dysfunction, then improvements in stroke volume (SV) or forward wave pressure (Pf) would be beneficial. Alternatively, if hypertension is the primary cause of systolic HF, aortic PP may be increased as a consequence of high aortic characteristic impedance (Zc) and backward wave pressure (Pb), which would be detrimental. Accordingly, blood pressure (BP) lowering would be advantageous. However, the changes in central hemodynamics that accompany systolic HF are currently unclear. Hence, I aimed to assess central hemodynamics in systolic HF patients compared to community participants. I therefore compared aortic haemodynamics (central pressures [SphygmoCor], aortic tract outflow [echocardiography]), and the impact of controlled BP (SBP/DBP<140/90 mm Hg or SBP/DBP<130/80 mm Hg) between stable systolic HF patients (n=42) and age and sex-matched community participants (n=298). Systolic HF patients had lower central PP and Pb (p<0.005) and higher HR (p<0.005) than community participants. However, no other differences were noted. When assessing the impact of BP control (SBP/DBP<140/90 mm Hg), HF patients with uncontrolled BP had higher Zc (p<0.005), Pf (p<0.05), and systemic vascular resistance (SVR) (p<0.05) than both HF patients and community participants with controlled BP. Moreover, despite similar peripheral and central PP to community participants with uncontrolled BP, Zc (p<0.005) and SVR (p<0.05) were higher in HF patients with uncontrolled BP. However, when assessing more intense BP control (SBP/DBP<130/80 mm Hg), the differences in Zc, QxZc, and SVR between the systolic HF patients with uncontrolled BP and the community participants with uncontrolled BP were eliminated. In conclusion, a lower aortic PP, which was not due to decreased SV, was observed in stable systolic HF patients. However, in the presence of uncontrolled BP (SBP/DBP≥140/90 mm Hg), but not SBP/DBP≥130/80 mm Hg, Zc, QxZc and SVR were increased in patients with systolic HF. Hence, BP control and its level of control are imperative in patients with systolic HF to protect the heart from the detrimental effects of increased afterloads.
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    Investigating the mechanism of action of Aristea ecklonii’s suspected antipyretic properties
    (University of the Witwatersrand, Johannesburg, 2024) Muller, Miles Christopher
    Aristea ecklonii (A. ecklonii) (Baker) is an indigenous, evergreen perennial medicinal plant used amongst South Africans to treat fever. This study aimed to investigate the antipyretic properties of aqueous A. ecklonii root extracts. Male Sprague-Dawley rats (250 – 300 g) received a subcutaneous (s.c.) injection of zymosan (300 mg/kg) or saline before receiving an intraperitoneal injection (i.p.) of paracetamol (50 mg/kg), aqueous A. ecklonii root extract (55 mg/kg) or saline. The i.p. injection was administered 15 h after the s.c. injection. Abdominal temperature was measured using temperature sensitive radio-transmitters. Blood, cerebrospinal fluid (CSF) and hypothalamic tissue was collected 90 min after the i.p. injection for the measurement of cytokines, prostaglandin E2 (PGE2) and enzymes involved in PGE2 synthesis. Zymosan increased abdominal temperature which peaked at 39.42 ± 0.14 °C. Compared to rats that received saline, rats receiving zymosan had increased concentrations of blood plasma IL- 1β and IL-6, increased PGE2 in the CSF and increased hypothalamic expression of COX-2 and mPGES1 (P < 0.05). Paracetamol and aqueous A. ecklonii root extract reduced the zymosan- induced fevers. Rats that received saline, followed by an i.p. injection of aqueous A. ecklonii root extract, had a decrease in abdominal temperature and an increase in blood plasma IL-1β, IL-6, TNF-α and IL-10 concentrations compared to rats that received saline (P < 0.05). Thus, the antipyretic properties of the A. ecklonii root extract seems to be related to its ability to induce systemic inflammation and not reduce the synthesis of hypothalamic PGE2 and thus should be used with caution in ill individuals.
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    Sexual dimorphism and renin-angiotensin-aldosterone system (RAAS) in hypertension and left ventricular hypertrophy in Spontaneously Hypertensive Rat (SHR)
    (University of the Witwatersrand, Johannesburg, 2024) Selebano, Kopano
    Background: The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and is linked to hypertensive left ventricular hypertrophy. Sex differences in the involvement of the RAAS in the development of hypertension and left ventricular hypertrophy are unclear, specifically in spontaneously hypertensive rats (SHRs). This study aimed to investigate the sexual difference in the RAAS effects on hypertension and ventricular remodelling in spontaneously hypertensive rats (SHRs). Methods: Thirty SHRs and Wistar Kyoto rats (WYKs) were assigned to four groups, namely; male SHR (n=8), female SHR (n=8), male WKY (n=7), and female WKY (n=7). Body weight, blood pressure and echocardiography parameters were measured before termination. Concentrations of RAAS parameters were measured using enzyme-linked immunosorbent assays (ELISA) at termination (after 7 months). The picrosirius red stain was used to determine collagen content in the left ventricle. Results: SHRs, in comparison to WKYs, had significantly higher blood pressure, greater heart and left ventricular mass, greater heart wall thickness, greater area of collagen and impaired left ventricular relaxation (reduced lateral e’), and increased filling pressures (increased E/e’) (p<0.05). SHRs also had significantly reduced end- diastolic volume, stroke volume and mid-wall fractional shortening (p<0.05). Females, in comparison to males, had reduced end-diastolic volume, stroke volume and mid- wall fractional shortening but had greater physiological growth (p<0.05). Female SHRs exhibited higher conscious and anaesthetised systolic and diastolic blood pressures, along with greater plasma concentrations of angiotensin II (ANG II) compared to other groups (p<0.05). v Conclusion: Compared to WKYs, SHRs developed concentric hypertrophy, impaired diastolic and systolic function. Compared to males, females developed greater physiological left ventricular growth with lower left ventricular relaxation and systolic function. The physiological cardiac differences may partly be influenced by factors such as body weight and blood volume. Additionally, female SHRs had elevated blood pressure, which may be due to increased plasma concentrations of ANG II.
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    Determination of Characteristic Impedance in a Retrospective Cohort of Coronary Artery Disease in South Africa
    (University of the Witwatersrand, Johannesburg, 2024) Els, Danelle; Peterson , Vernice R.; Peters, Ferande
    The relationship between coronary artery disease (CAD) and proximal aortic stiffness-induced increases in central arterial forward wave pressures (Pf) is uncertain. Using central pressure and aortic velocity and diameter measurements, we compared aortic characteristic impedance (Zc) (n=71) and central arterial pressure wave morphology (n=189) in patients with CAD to central arterial function in 210 age- and sex-matched controls from a community study. The results showed that Zc was markedly increased in patients with CAD compared to community controls (p<0.0001). In addition, after adjustment for mean arterial pressure and aortic root diameter, the early systolic pressures generated by the product of peak aortic flow (Q) and Zc (PQxZc) and Pf were markedly increased in patients with CAD as compared to controls (p<0.0001). This increase in Pf was accounted for by an enhanced PQxZc at peak PPc rather than increases in re-reflected wave pressures. Further adjustments for either brachial PP or systolic blood pressure (SBP) showed that higher Pf values were retained in the CAD patients (p<0.05, p<0.01, p<0.0001). After adjusting for conventional risk factors, peak central aortic PPc was higher in patients with CAD as compared to controls (p<0.05, p<0.005, p<0.0001). However, after adjusting for brachial SBP and confounders, central aortic PPc did not differ between the groups. Thus, increases in stiffness-associated proximal aortic Zc in patients with CAD translate into marked increases in Pf, but not peak PPc beyond brachial BP. These findings suggest that pulsatile load responsible for CAD is beyond brachial BP and poorly indexed by peak PPc.
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    The Impact of Urinary Uromodulin (Tamm-Horsfall Protein) on Renal Function and Haemodynamic Factors in a Community Sample with a High Prevalence of Hypertension
    (University of the Witwatersrand, Johannesburg, 2024) Charles, Aaliah; Peterson, Vernice
    Populations of African ancestry have a high prevalence of primary hypertension and its comorbidities. As they primarily exhibit a volume-dependent form of hypertension, the role of nephron components needs to be explored. Uromodulin is a potential biomarker for renal function and tubular reserve; however, its relationship with renal function, haemodynamic parameters, and hypertension in a population of African ancestry is unknown. I therefore explored the relationship between urinary uromodulin (uUMOD) concentration and renal as well as hemodynamic parameters in an African community with a high prevalence of volume-dependent hypertension. Haemodynamics (central pressures [SphygmoCor], echocardiographic aortic velocity and diameter in the outflow tract), uUMOD concentrations (ELISA assay), renal function (creatinine clearance from 24-hour urine [n = 370]) were determined in a community of African ancestry (n = 397). No relationships between uUMOD concentrations and renal function, age, BMI, BP or hypertension were noted. However, uUMOD concentrations were higher in females than males, even after adjusting for confounders (P = 0.0007). An inverse relationship was observed between stroke volume (SV) and uUMOD (P = 0.0023). This inverse relationship was independent of confounders and present in hypertensives (P= 0.007) but not normotensives (P = 0.43). Hypertensives had a higher SV than normotensives (P = 0.047). In a community sample with a high prevalence of volume-dependent primary hypertension, uUMOD was inversely related to SV, particularly in hypertensives. Although uUMOD is not a biomarker for renal function in this population, these data suggest the need to investigate mechanisms linking uUMOD to SV to assist in identifying novel pathways to better treat volume-dependent hypertension.
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    Effects of Supplemental Zingerone on Cobb 500 Broiler Chicken (Gallus gallus domesticus) Growth Performance, Health and Meat Quality
    (University of the Witwatersrand, Johannesburg, 2023-07) Mdoda, Bayanda; Chivandi, Eliton; Lembede, Busisani Wiseman
    Commercial broiler and pullet chicken producers supplement chicken diets with sub-therapeutic doses of antibiotics such as zinc bacitracin that act as growth promoters to enhance production performance, meat and egg quality. Use of these antibiotics as growth promoters, in addition to causing environmental pollution, causes the public health challenge of antibiotic resistance which compromises poultry and consumer, hence the need to search for environmentally friendly and health-friendly alternatives to antibiotics. Phytochemicals, zingerone included, display biological activities similar to those of antibiotics. This study evaluated zingerone`s potential to replace bacitracin (ZnBcn) as a growth-promoting diet supplement in broiler feed specifically determining its effects on growth performance, meat quality and bird health. One hundred and twenty unsexed 1-day-old Cobb 500 broiler chicks (10 chicks per replicate with 3 replicates per diet) were randomly assigned to four dietary treatments where zingerone replaced ZnBcn at: diet 1 – 0 mg kg-1 (control: 500 mg akg-1 of zinc bacitracin); diet 2 – 40 mg kg-1; diet 3 – 80 mg kg-1 and diet 4 – 120 mg kg-1 in the starter, grower and finisher diets. The broiler chicks were fed ad libitum for 6 weeks: starter (week 1-2), grower (week 3-4), and finisher (week 5-6). Initial and weekly body mass, daily feed intake (FI), and terminal body mass (TBM) were measured. Body mass gain (BMG), average daily gain (ADG), and feed conversion ratio (FCR) were computed. On day 42, the chickens were humanely slaughtered, blood collected and carcasses dressed. The gastrointestinal tract (GIT) and accessory GIT viscera organs were weighed and small and large intestine lengths were measured. Empty carcass masses were measured and the dressing percentages were computed. Viscera macromorphometry, long bone indices and carcass traits, the meat’s physical quality [initial and ultimate pH (pHi and pHu), colour, thawing loss (TL), cooking loss (CL), and tenderness] traits, proximate and amino acid content and fatty acid profiles were measured. Plasma malonaldehyde (MDA) concentration, glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities, surrogate markers of liver and kidney function, liver fat content and histology were determined. Across growth phases and overall, dietary zingerone had similar effects (p > 0.05) as ZnBcn on the chicken’s TBM, BMG, ADG, FI, and FCR. It also had similar effects (p > 0.05) as ZnBcn on the chicken’s empty carcass mass, dressing percentage, long bone indices and viscera macromorphometry. Dietary zingerone had similar (p > 0.05) effects as ZnBcn on the broiler chicken meat’s pHi, pHu, CL, TL and tenderness. However, at 40 mg kg-1 of feed (diet 2) it increased the meat’s redness (a*) compared to that of counterparts fed the ZnBcn-fortified control diet. Furthermore, supplemental zingerone had a similar effect to that of ZnBcn on the meat’s crude protein content but it significantly increased the meat’s ash and fat contents (p < 0.01; p < 0.0001). Meat from chickens fed diet 2 (40 mg kg-1 of feed zingerone) had the highest concentration of essential amino acids (p < 0.05) and that from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had the lowest (p > 0.001) total amino acid content. Dietary zingerone had a similar (p > 0.05) effect as ZnBcn on the chicken meat’s total saturated fatty acids, but breast meat from chickens fed diets 3 (80 mg kg-1 of feed zingerone) had significantly increased (p < 0.0001) total monounsaturated fatty acid and oleic acid content. Meat from chicken-fed diet 4 (120 mg kg-1 of feed zingerone) had the highest total polyunsaturated fatty acid and linoleic acid content and a higher PUFA:SFA ratio compared to that from counterparts fed diets 1, 2 and 3. Supplemental zingerone had similar effects (p > 0.05) as ZnBcn on the chickens’ liver masses and fat contents, plasma MDA concentration, GSH-Px, GST, SOD, CAT, alkaline phosphatase, alanine transaminase activities, albumin, total bilirubin, creatinine and urea concentrations. Chickens’ hepatic inflammation and steatosis scores were similar across diets (p > 0.05). At 120 mg kg-1 of feed zingerone, though similar to the control, supplemental zingerone decreased the chickens’ plasma globulin and total protein concentration (p < 0.01; p < 0.05) compared to counterparts supplemented at low and medium dose of zingerone. Zingerone can be used as a growth promoter in place of zinc bacitracin in broiler chicken diets without compromising growth, feed use efficiency, carcass yield, long bone and GIT viscera growth and development, the meat’s pH, CL, TL and tenderness. Furthermore, it can be used without eliciting oxidative stress in the birds and with no risk to kidneys, liver and general health of the birds. Importantly, zingerone, as a dietary supplement, can be used to enhance broiler chicken meat’s redness, positively impacting its acceptability and meat’s total monounsaturated, oleic acid, total polyunsaturated and linoleic acid fatty acid profile; thus improving its nutritional value.
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    The potential of zingerone to protect against alcohol-induced liver disease
    (University of the Witwatersrand, Johannesburg, 2023-05) Asiedu, Bernice; Chivandi, Eliton; Nyakudya, Trevor; Lembede, Busisani
    Alcohol can cross the placental blood-barrier and can also be secreted into breast milk. This can affect developing foetuses and/or nursing neonates negatively, thus impacting on metabolic health in early or later life. Zingerone (ZO) has anti-oxidant, anti-diabetic, anti-inflammatory, hypolipidaemic and hepato-protective properties. I hypothesised that neonatal oral administration of ZO could programme for protection against alcohol-induced metabolic derangements in suckling Sprague-Dawley (SD) rat pups mimicking human neonates that indirectly consume alcohol through their mother’s breast milk. The first experiment evaluated ZO’s potential to protect suckling rat pups against alcohol-induced metabolic derangements. Seventy 10-day old SD rat pups (males = 35; females = 35) were randomly assigned to four groups and administered treatments daily from postnatal (PND) 12-21: group 1-nutritive milk (NM), group 2-1 g/kg body mass ethanol (Eth), group 3-40 mg/kg body mass ZO and group 4 - NM+Eth+ZO. Terminal body mass, blood glucose concentration, lipid profile and hepatic antioxidant status were determined. Zingerone and ethanol had no effect on pups’ growth performance, blood glucose, total cholesterol, HDL- and LDL-cholesterol and hepatic thiobarbituric acid (TBARs), superoxide dismutase and catalase concentrations (p > 0.05). Ethanol decreased plasma triglyceride concentration in female rat pups (p = 0.04) but increased hepatic cytochrome P450E21 (CYP2E1) and decreased total glutathione (tGSH) concentration in male rat pups (p < 0.05). Zingerone increased tGSH in male rat pups (p = 0.003). A combination of ZO and ethanol increased (p = 0.047) hepatic CP2E1 concentration in male rat pups compared to control but had no effect (p = 0.717) on tGSH concentration. Neonatal orally administered ethanol induced hepatic oxidative stress which ZO, administered during the suckling period, failed to protect against. In experiment II, 123 SD rat pups (males = 60; females = 63) were administered the same neonatal interventions as in experiment I but from PDN22 they were grown to adolescence (PND45) with ad libitum access to normal rat chow and tap water. From PND 46-100, rats from each of the four neonatal groups were divided into two subgroups: subgroup I had tap water and subgroup II had ethanol solution as drinking fluids, for eight weeks. Body mass, feed, fluid and caloric intake were measured. Blood glucose concentration, plasma alanine transaminase and aspartate transaminase (ALT and AST) activities, adiponectin (ADP), leptin (LEP) and insulin (INS), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cytochrome P4502E1 (CYP2E1) concentrations were measured. HOMA-IR was computed. Visceral fat mass, hepatic fat content and histomorphometry were assessed. Hepatic TBARs and mRNA expressions of peroxisome proliferator activator receptor-alpha (PPAR-α), sterol regulatory element binding protein 1c (SREBP1c), nuclear factor kappa beta (NF-Kβ) and TNF-α were measured. Ethanol consumption in adulthood decreased feed and fluid intake but increased calorie intake and plasma CYP2E1 concentration (p < 0.05 vs control). It decreased blood glucose concentration of male rats (p = 0.026). A late single- and a double-alcohol hit had no effect on body and visceral fat mass of the rats (p > 0.05). Neonatal orally administered zingerone and ethanol and consumption of ethanol in adulthood had no effect on body mass, plasma lipid profile, adiponectin, leptin and insulin concentrations, HOMA-IR, AST and ALT activities, IL-6, TNF-α and hepatic TBARS and mRNA expression of NF-KB and TNF-α (p >0.05). A late single hit with ethanol increased hepatic fat content of male rats only (p = 0.014). A double and or late single ethanol hit increased liver fat content in female rats (p < 0.05). Both a late single and double ethanol hit downregulated PPAR-α but upregulated SREBP1c expression in male and female rats (p < 0.05) and it caused the development of large droplet macrosteatosis. A combination of neonatal orally administered ZO and a late single ethanol hit decreased visceral fat mass of female rats (p = 0.045 vs control) but it did not affect the blood glucose concentration of male rats (p > 0.05). Neonatal orally administered ZO with either a late single- or a double-ethanol hit caused hepatic macrosteatosis, but it had no effect on mRNA expression of PPAR-α of the rats (p > 0.05). However, neonatal orally administered ZO in combination with a late single ethanol hit did not affect SREBP1c expression of the rats but a combination of neonatal orally administered ZO with a double ethanol hit increased SREBP1c expression of female rats (p = 0.005). The responses of the rats to interventions showed sexual dimorphism: ethanol consumption in adulthood decreased blood glucose concentration of male rats only and an early single ethanol hit caused microsteatosis only in female rats. Zingerone protected male rats against ethanol-induced hepatic fat accumulation. It attenuated the ethanol-induced upregulation of hepatic SREPB1c expression in males but not in females. Ethanol (late single and/or double hit) downregulated the hepatic PPAR-α expression in the rats which was mitigated by ZO. Neonatal orally administered ZO attenuated the late single- and double-hit ethanol-induced macrosteatosis in the rats. Thus, neonatal orally administered ZO can potentially be used as a prophylactic agent against ethanol-induced hepatic lipid accumulation in males and steatosis in both males and females.