Browsing by Author "Bbosa, Godfrey S."

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Aflatoxins metabolism, effects on epigenetic mechanisms and their role in carcinogenesis
    (Health, 2013) Bbosa, Godfrey S.; Kitya, David; odda, John; Ogwal-Okeng, Jasper
    Chronic consumption of aflatoxin-contaminated foods is a global problem in both developing and developed countries especially where there is poor regulation of their levels in foods. In the body, aflatoxins (AFBs) mainly AFB1 are bio- transformed to various metabolites especially the active AFB1-exo-8,9-epoxide (AFBO). The AFB, AFBO and other metabolites interact with various biomolecules in the body including nu- cleic acids such as DNA and RNA and the vari- ous metabolic pathways such as protein syn- thesis, glycolytic pathway and electron trans- port chain involved in ATP production in body cells. The AFB interacts with DNA to form AFB- DNA adducts causing DNA breakages. The AFB and its metabolites induce the up regulation of nuclear receptors such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), and aryl hydrocarbon receptor (AhR) through gene expression that regulates the metabolizing enzymes such as CYP450 involved in Phase I and Phase II metabolism of xenobiotics. AFB ac- tivates these nuclear receptors to produce the metabolizing enzymes. The AFB1 is metabolized in the body by cytochrome P450 (CYP450) enzyme isoforms such as CYP1A2, CYP1A2, CYP3A4/ CYP3A5, and CYP3A7 in fetus, glutathione S- transferase, aflatoxin B1-aldehyde reductase leading to reactive metabolites, some of which can be used as aflatoxin exposure biomarkers. These enzymes are involved in the Phase I and Phase II metabolic reactions of aflatoxins. The CYP1A2 is the principal metabolizer of aflatoxin at low concentrations while the reverse is true for CYP3A4. The accumulation of AFB and its metabolites in the body especially the AFB1-exo-8,9-epoxide depletes the glutathione (GSH) due to the formation of high amounts of epoxides and other reactive oxygen species (ROS). The AFB, AFB1-exo-8,9-epoxide and other metabo- lites also affect the epigenetic mechanisms in- cluding the DNA methylation, histone modifica-tions, maturation of miRNAs as well as the daily formation of single nucleotide polymorphism (SNP) where AFB exposure may facilitate the process and induces G:C to T:A transversions at the third base in codon 249 of TP53 causing p53 mutations reported in hepatocellular carcinoma (HCC). The changes in epigenetic mechanisms lead to either epigenetic inactivation or epige- netic derepression and all these affect the gene expression, cellular differentiation and growth. AFB also through epigenetic mechanisms pro- motes tumorigenesis, angiogenesis, invasion and metastasis in hepatocellular carcinoma. However, the formation of the small amounts of AFB1 from AFB2 is suspected to cause the carcinogenicity of AFB2 in humans and animals. Chronic afla- toxins exposure leads to formation of reactive AFBO metabolites in the body that could acti- vate and de-activates the various epigenetic me- chanisms leading to development of various cancers.
  • Thumbnail Image
    Item
    Anti-Plasmodium falciparum activity of Aloe dawei and Justicia betonica
    (African Journal of Pharmacy and Pharmacology, 2013) Bbosa, Godfrey S.; Kyegombe, David B.; Lubega, Aloysius; Musisi, Nathan; Ogwal-Okeng, Jasper; Odyek, Olwa
    Malaria is a fatal disease caused by different Plasmodium species of parasites and has remained the major killer of humans worldwide especially the children under five years of age and pregnant women. In this study, the anti-Plasmodia activities of the crude leaf ether extracts of Aloe dawei (AD) and Justicia betonica (JB) on Plasmodium falciparum were investigated, with chloroquine diphosphate as a positive control. The results showed that ether extracts of JB had EC50 of 13.36 (95% CI: 8.032 to 22.23) μg/ml and AD had 7.965 (95% CI: 3.557 to 17.84) μg/ml. The chloroquine diphosphate had EC50 of 24.86 (95% CI: 9.239 to 66.89) μg/ml. The qualitative phytochemical analysis of the ether extract showed that JB contains steroids and triterpenoids, alkaloids and saponins while AD contained steroids and triterpenoids, anthraquinolones, alkaloids and saponins. The results provides evidence that JB and AD contain compounds with anti-P. falciparum activity and hence their use by the traditional herbalist and local communities in treatment of malaria.
  • Thumbnail Image
    Item
    Chronic alcohol use reduces CD4+counts in HIV/AIDS patients on d4T/3TC/NVP treatment regimen using WHO AUDIT tool and alcohol-use biomarkers
    (Research & Reviews in BioSciences, 2014) Bbosa, Godfrey S.; Kyegombe, David B.; Anokbonggo, William W.; Mugisha, Apollo; Ogwal-Okeng, Jasper
    Alcohol is one of the most abused drugs worldwide by people of different socio-economic status, age groups and including the HIV/AIDS patient on treatment. It is reward drug and a CNS depressant especially at high doses. The study investigated effect of chronic alcohol exposure by HIV/ AIDS patients on d4T/3TC/NVP regimen on CD4+counts inUganda using WHO AUDIT tool and chronic alcohol-use biomarkers. A longitudinal cohort using repeated measures design with serial measurements model was used. TheWHOAUDIT toolwas used to screen patients on stavudine (d4T) 30mg, lamivudine (3TC) 150mg and nevirapine (NVP) 200mg for chronic alcohol use.Atotal of 41 patients (20 alcohol group and 21 control group) were screened for chronic alcohol use. They were followed up for 9 months with blood sampling done at 3 month intervals. CD4+ count was determined using Facscalibur Flow Cytometer equipment. Results were then sorted by alcohol-use biomarkers (GGT, MCV and AST/ALT ratio). Data was analysed using SAS 2003 version 9.1 statistical package with repeatedmeasures fixedmodel and themeanswere compared using student t-test. Themean CD4+ count in all groups were lower than reference ranges at baseline and gradually increased at 3, 6 and 9 month of follow up. The mean CD4+ count in control group were higher in the control group as compared to the chronic alcohol use group in both WHO AUDIT tool group and chronic alcohol-use biomarkers group though there was no significant difference (p>0.05). Chronic alcohol use slightly lowers CD4+ cell count in HIV/AIDS patients on d4T/3TC/NVP treatment regimen.
  • Thumbnail Image
    Item
    Chronic ethanol use in alcoholic beverages by HIV-infected patients affects the therapeutic window of stavudine, lamivudine and nevirapine during the 9-month follow-up period: using chronic alcohol-use biomarkers
    (Journal of Basic and Clinical Physiology and Pharmacology, 2013) Bbosa, Godfrey S.; Kyegombe, David B.; Anokbonggo, William W.; Ogwal-Okeng, Jasper; Musoke, David; Odda, John; Lubega, Aloysius; Ntale, Muhammad
    Background: Chronic ethanol use is a global problem including among HIV-infected patients on stavudine/ lamivudine/nevirapine (d4T/3TC/NVP) regimen. The study determined the effect of chronic ethanol use on the therapeutic window of d4T, 3TC and NVP in HIV-infected patients using alcohol-use biomarkers to screen patients for chronic ethanol use. Methods: A case-control study using repeated measures design with serial measurements was used to quantify drugs in plasma. The WHO alcohol use disorder identification test (AUDIT) tool was initially used to screen patients for chronic alcohol use, and then they were further sorted using alcohol-use bioamarkers (γ-glutamyl transferase ≥ 55.0 IU; mean corpuscular volume, ≥ 96 fl, aspartate amino transferase/ alanine aminotransferase ratio ≥ 2.0 value). A total of 41 patients (26 in the alcohol group and 15 in the control group) were followed up for 9 months with blood sampling done at 3-month intervals. Plasma drug concentrations were quantified using a Shimadzu Class-VP™ HPLC data system version 6.1. Data was analyzed using SAS 2003 version 9.1 statistical package with repeated measures fixed model. Means were compared using Student’s t-test. Results: The mean steady-state plasma drug concentrations of d4T and 3TC in the alcohol group were lower than that in the control group during the 9-month period of follow-up. For 3TC, there was a statistical difference in the mean steady-state plasma drug concentrations between the alcohol group and the control group (p ≤ 0.05) in the 6- and 9-month period of follow-up. For NVP, in both groups they were within the reference ranges, although the drug plasma concentrations were higher in the alcohol group compared to the control group and were statistically significant (p < 0.05) in 0, 3 and 6 months of follow-up. Conclusions: Chronic ethanol use by HIV-infected patients reduced the therapeutic steady-state plasma drug concentrations of d4T and 3TC and increased the NVP drug concentrations in the HIV-infected patients.
  • Thumbnail Image
    Item
    Effect of the total crude extracts of Hibiscus sabdariffa on the immune system in the Wistar albino rats
    (African Journal of Pharmacy and Pharmacology, 2013) Lubega, Aloysius M.B.; Bbosa, Godfrey S.; Musisi, Nathan; Erume, Joseph; Ogwal-Okeng, Jasper
    Medicinal herbs are commonly used worldwide as immune boosters and immunomodulators in the management of various disease conditions. Many of these herbs commonly used have not been scientifically evaluated for their immune modulating activities. The study investigated the immunomodulatory activity of the total crude leaf extract of Hibiscus sabdariffa in Wistar albino rats. It was an experimental study that was conducted on four groups of animals each with 6 healthy adult rats. Group I was dosed each with 1mL of normal saline. Groups II, III and IV were dosed 1mL of 125, 250 and 500 mg/Kg bwt of total crude extract, daily for 14 days respectively. On the 15th day, whole blood was collected into a clean ethlenediaminetetracetic acid (EDTA)-vacutainer. The complete blood count (CBC), immune blood cell count, hemagglutination antibody (HA) titers, neutrophil adhesion and delayed-type hypersensitivity (DTH) response were determined. All the doses caused an increase in mean red blood cell (RBC) counts as compared to control group. Similarly, the mean percentage neutrophils, monocytes, basophils and eosinophils increased with dose while the opposite was true for percentage lymphocytes. The mean HA titers for the herb were higher than control though no statistical difference (p≥0.05) was observed. Similar effects were observed with neutrophil adhesions response as that of HA titers. For DTH, the highest footpad thickness (175.2% increment) was observed at a dose of 500 mg/Kg bwt after 12 h and was statistically significant (p≤0.05) as compared to control. H. sabdariffa contain compounds with immunomodulatory activity in Wistar albino rats.
  • Thumbnail Image
    Item
    Review of the Biological and Health Effects of Aflatoxins on Body Organs and Body Systems
    (InTech, 2013) Bbosa, Godfrey S.; Kitya, David; Lubega, A.; Ogwal-Okeng, Jasper; Anokbonggo, William W.; Kyegombe, David B.
    Aflatoxins are a group of naturally occurring carcinogens that are known to contaminate different human and animal food stuffs. Aflatoxins are poisonous by-products from soil-borne fungus Aspergillus, which is responsible for the decomposition of plant materials [1-9]. The occurrence of aflatoxins foods and food products vary with geographic location, agricultural and agronomic practices. The susceptibility of food product to fungal attack occurs during pre-harvest, transportation, storage, and processing of the foods [1, 2, 4, 6, 9, 10]. The problem of aflatoxin contamination of the food products is a common problem in tropical and subtropical regions of the world especially in the developing countries such as the sub-Saharan countries with poor practices and where the environmental conditions of warm temperatures and humidity favors the growth fungi [1, 2, 4, 6, 9, 10]. The various food products contaminated with aflatoxins include cereals like maize, sorghum, pearl millet, rice and wheat; oilseeds such as groundnut, soybean, sunflower and cotton; spices like chillies, black pepper, coriander, turmeric and zinger; tree nuts such as almonds, pistachio, walnuts and coconut; and milk and milk products [11].