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    Pilani Nkomozepi

    Diabetes, alcohol abuse, and combination antiretroviral therapy (cART) use have been reported to cause multi-organ complications via induction of oxidative stress and inflammation. Moreover, these are the most common factors implicated in... more
    Diabetes, alcohol abuse, and combination antiretroviral therapy (cART) use have been reported to cause multi-organ complications via induction of oxidative stress and inflammation. Moreover, these are the most common factors implicated in male reproductive dysfunctions. This study evaluated testicular oxidative stress, inflammation, apoptosis, and germ cell proliferation in diabetic rats receiving alcohol or cART and their combination. Thirty adult male Sprague Dawley rats were divided into five groups, each consisting of six rats; control, diabetic only (DM), diabetic treated with alcohol (DM + A), diabetic treated with cART (DM + cART), and diabetic treated with both alcohol and cART (DM + A + cART). After 90 days of treatment, the rats were terminated, and the testes were extracted and processed for immunohistochemistry analysis for oxidative stress, inflammatory cytokines, apoptosis, and cell proliferation marker. In comparison to the control, oxidative stress markers, inducible...
    Kola nut is commonly consumed by pregnant women to suppress symptoms of morning sickness. This study investigated the effects of kola nut on the biochemical indices of the hippocampus and its dependent memory. Kola nut extract was fed to... more
    Kola nut is commonly consumed by pregnant women to suppress symptoms of morning sickness. This study investigated the effects of kola nut on the biochemical indices of the hippocampus and its dependent memory. Kola nut extract was fed to pregnant dams from the first day of their pregnancy until parturition. The following behavioral function tests were conducted: surface righting (SR); cliff avoidance (post-natal day [PND] 4, 5, 6 & 7); open field; novel object recognition and location; and radial-arm maze (PND 21 and 56). The levels of brain-derived neurotrophic factor (BDNF), acetylcholine (ACh), and malondialdehyde (MDA) of the matched hippocampal tissues were also checked in the pups. The kola nut-treated pups showed significantly reduced behavioral indices compared to the pups in the control group: lower postural balance, higher risk avoidance memory, and lower frequency in pivoting and rearing compared to that in the control group. However, the frequency of urine and fecal bolu...
    The prevalence of diabetic patients who abuse alcohol while on combination antiretroviral drug therapy (cART) therapy is rising in society. Little is known about the impact of this scenario on the testes and male reproductive viability,... more
    The prevalence of diabetic patients who abuse alcohol while on combination antiretroviral drug therapy (cART) therapy is rising in society. Little is known about the impact of this scenario on the testes and male reproductive viability, and therefore, these factors were evaluated. Thirty 10-week-old male Sprague Dawley rats were distributed into five groups of six rats each: control, diabetic only (DM), diabetic treated with alcohol (DM+A), diabetic treated with Atripla, fixed-dose cART (DM+cART), and diabetic treated with both alcohol and cART (DM+A+cART). After 90 days of treatment, rats were terminated, and blood and testes were harvested for immunoassay, histological, and immunohistochemistry analyses. Testicular perturbations of varying severity were recorded in all treated groups for most of the parameters. The DM+A treated group showed the most severe perturbations, followed sequentially by the treated groups DM+A+cART, DM, and DM+cART. Alterations in the testes and seminifer...
    Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is highly prevalent in Type 2 diabetes mellitus (T2DM). NASH progresses into cirrhosis and hepatocellular carcinoma and is known to worsen the... more
    Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is highly prevalent in Type 2 diabetes mellitus (T2DM). NASH progresses into cirrhosis and hepatocellular carcinoma and is known to worsen the prognosis and mortality in T2DM. Our understanding of the mechanisms underlying NASH development in T2DM is hindered by the absence of a good animal model that can physiologically develop T2DM and NASH. This study investigated the potential of the Zucker Diabetic Sprague Dawley (ZDSD) rat as a suitable model for studying T2DM-related NASH. Eight, twenty-week old ZDSD rats which became diabetic at week sixteen, were compared with six age-matched, non-diabetic Sprague Dawley (SD) rats. We measured body mass gain, fasting glucose, fasting triglycerides and glucose handling pre and post diabetic onset. We also measured circulating levels of the liver function enzymes; alanine transaminase and alkaline phosphatase, and other surrogate markers of kidney ...
    Atrazine (ATZ) is an herbicide commonly detected in groundwater. Several studies have focused on its immunological and endocrine effects on adult Xenopus laevis species. However, we investigated the impact of atrazine on the renal and... more
    Atrazine (ATZ) is an herbicide commonly detected in groundwater. Several studies have focused on its immunological and endocrine effects on adult Xenopus laevis species. However, we investigated the impact of atrazine on the renal and hepatic biochemistry and histomorphology in adult male frogs. Forty adult male frogs were allocated to four treatment groups (control, one ATZ (0.01 µg/L), two ATZ (200 µg/L) and three ATZ (500 µg/L), 10 animals per group, for 90 days. Alanine aminotransferase (ALT) and creatinine levels increased significantly (p < 0.05) in the 200 and 500 μg/L groups but malondialdehyde only in the 500 μg/L group (p < 0.05). Histopathological observations of derangement, hypertrophy, vascular congestion and dilation, infiltration of inflammatory cells incursion, apoptosis and hepatocytes cell death were observed with atrazine exposure, mostly in the 500 μg/L group. Additionally, histochemical labelling of caspase-3 in the sinusoidal endothelium was observed in ...
    High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced... more
    High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced NAFLD later in adulthood. We investigated the protective potential of chrysin against fructose-induced NAFLD. Four-day-old male and female suckling Sprague Dawley rats (N = 112) were randomly grouped and orally gavaged daily with distilled water (negative Control-Cn + W), chrysin(Chr-100 mg/kg), fructose-solution (Fr-20% w/v), and Chr + Fr between postnatal day (PND) 4 and 21 and then weaned onto normal rat chow and plain drinking water to PND 55. From PND 56 to 130, half of the rats continued on plain water, and the rest had Fr as drinking fluid. Terminally, the liver tissue was collected, and the lipid content was determined and histologically assessed for NAFLD. Dietary Fr induced an increased hepatic lipid content (p = 0.0001 vs. Cn + W) both s...
    Congenital anomalies such as ventricular septal defects and truncus communis have been reported with the prenatal use of antiretroviral therapy. The mechanism of antiretroviral therapy teratogenicity is unclear and is therefore the focus... more
    Congenital anomalies such as ventricular septal defects and truncus communis have been reported with the prenatal use of antiretroviral therapy. The mechanism of antiretroviral therapy teratogenicity is unclear and is therefore the focus of this study. Some human immunodeficiency virus patients on antiretrovirals are placed on antiepileptic drugs which are also teratogenic. The interactive effects arising from this therapeutic combination may affect their teratogenic propensity through their effects on neural crest cell migration.
    BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against... more
    BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We 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 children fed obesogenic diets. METHODS: Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocat-ed 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...
    Despite several reports on the endocrine-disrupting ability of atrazine in amphibian models, few studies have investigated atrazine toxicity in the heart and cerebellum. This study investigated the effect of atrazine on the unique Ca2+... more
    Despite several reports on the endocrine-disrupting ability of atrazine in amphibian models, few studies have investigated atrazine toxicity in the heart and cerebellum. This study investigated the effect of atrazine on the unique Ca2+ channel-dependent receptor (Inositol 1,4,5-trisphosphate; IP3R) in the heart and the cerebellum of adult male Xenopus laevis and documented the associated histomorphology changes implicated in cardiac and cerebellar function. Sixty adult male African clawed frogs (Xenopus laevis) were exposed to atrazine (0 µg/L (control), 0.01 µg/L, 200 µg/L, and 500 µg/L) for 90 days. Thereafter, heart and cerebellar sections were processed with routine histological stains (heart) or Cresyl violet (brain), and IP3R histochemical localization was carried out on both organs. The histomorphology measurements revealed a significant decrease in the mean percentage area fraction of atrial (0.01 µg/L and 200 µg/L) and ventricular myocytes (200 µg/L) with an increased area ...
    Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred... more
    Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21–P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructos...
    Background Terminalia sericea (T. sericea) is traditionally used to treat stomach ailments, infections, hypertension and diabetes mellitus. Previous in vitro studies have reported that T. sericea has lipolytic properties. This study... more
    Background Terminalia sericea (T. sericea) is traditionally used to treat stomach ailments, infections, hypertension and diabetes mellitus. Previous in vitro studies have reported that T. sericea has lipolytic properties. This study interrogated the effects of T. sericea on linear growth, development of fatty liver disease, viscera morphometry and health of growing rats fed a 12% fructose solution (FS). Methods Thirty 21-day old male Wistar rat pups were randomly allocated to five treatments: group I - plain gelatine cubes (PGC) + plain tap water (PW), group II - 12% FS + PGC, group III - gelatine cubes containing fenofibrate (Feno) at a dose of 100 mg/kg body + FS, group IV - gelatine cubes containing the low dose (100 mg/kg body mass per day) of the T. sericea extract (TsL) + FS, group V - gelatine cubes containing the high dose (400 mg/kg body mass per day) of the T. sericea extract (TsH) + FS. Following 12 weeks of feeding, the rats were fasted overnight, euthanized and plasma a...
    Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated... more
    Dietary manipulations during the early postnatal period are associated with the development of metabolic disorders including non-alcoholic fatty liver disease (NAFLD) or long-term protection against metabolic dysfunction. We investigated the potential hepatoprotective effects of neonatal administration of oleanolic acid (OA), a phytochemical, on the subsequent development in adulthood, of dietary fructose-induced NAFLD. Male and female suckling rats (n=112) were gavaged with; distilled water (DW), OA (60 mg/kg), high fructose solution (HF; 20% w/v) and OA+HF (OAHF) for 7 days. The rats were weaned onto normal rat chow on day 21 up to day 55. From day 56, half of the rats in each treatment group were continued on plain water or HF as drinking fluid for 8 weeks. Hepatic lipid accumulation and hepatic histomorphometry were then determined. Fructose consumption in adulthood following neonatal fructose intake (HF+F) caused a 47–49% increase in hepatic lipid content of both male and femal...
    S-allyl cysteine (SAC) has antioxidant, antidiabetic and antiobesity properties. We hypothesized that neonatal oral administration of SAC would protect rats against neonatal and adulthood high-fructose diet-induced adverse metabolic... more
    S-allyl cysteine (SAC) has antioxidant, antidiabetic and antiobesity properties. We hypothesized that neonatal oral administration of SAC would protect rats against neonatal and adulthood high-fructose diet-induced adverse metabolic outcomes in adulthood. In total, 112 (males=56; females=56), 4-day-old Wistar rat pups were randomly allocated to groups and administered the following treatment regimens daily for 15 days from postnatal day (PND) 6–20: group I – 10 ml/kg distilled water, group II – 10 ml/kg 20% fructose solution (FS), group III – 150 mg/kg SAC and group IV – SAC+FS. On PND 21, the pups were weaned and allowed to grow on a standard rat chow (SRC) until PND 56. The rats from each treatment regimen were then randomly split into two subgroups: one on a SRC and plain drinking water and another on SRC and 20% FS as drinking fluid and then subjected to these treatment regimens for 8 weeks after which they were euthanized and tissues collected for analyzes. Neonatal oral admini...
    Fructose contributes to the development of nonalcoholic fatty liver disease (NAFLD). β-Sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential... more
    Fructose contributes to the development of nonalcoholic fatty liver disease (NAFLD). β-Sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential protective effect of β-sitosterol against NAFLD in growing rats fed a high-fructose diet, modelling children fed obesogenic diets. Forty-four 21 day old male rat pups were randomly allocated to and administered the following treatments for 12 weeks: group I, standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II, SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III, SRC + FS + 100 mg/kg fenofibrate in a gelatine cube; group IV, SRC + FS + 20 mg/kg β-sitosterol gelatine cube (Bst); group V, SRC + PW + Bst. Terminally, the livers were dissected out, weighed, total liver lipid content determined, and histological analyses done. Harvested plasma was used to determine the surrogate biomarkers of liver func...