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Patulin (PAT) is a mycotoxin produced by Penicillium and other fungi that contaminate fruit. PAT targets the kidney and is associated with nephrotoxicity. Micro-RNAs (miRNA) may offer new insights into PAT-induced nephrotoxicity. Cytochrome P

Unique characteristics displayed by phytoconstituent conjugated nanoparticles and their crucial interactions with proteins serve to develop nanoparticle-bio-interface platform. Gold nanoparticles of 16 nm in size were generated using aqueous extracts of pine bark and further conjugated to human serum albumin. The gold nanoparticles-protein complex was characterized by surface plasmon resonance, UV–vis and emission spectroscopy techniques. Further, it was characterized for surface morphology and elemental composition, crystallographic quality, nanoparticles size, shape, stability, structural determination and the identification of capping agent. Moreover, the interaction of gold nanoparticles with human serum albumin was investigated using conventional spectroscopy techniques. Fluorescence quenching and absorption studies demonstrated an effective binding of human serum albumin with oleamide capped gold nanoparticles. The molecular docking study showed a binding affinity of -6.1 kcal/mol whereas the molecular dynamics simulation indicated that the binding of oleamide to human serum albumin. A biological evaluation of pine bark extract-gold nanoparticles showed cytotoxicity with increased cell mortality in lung cancer cells and minimal toxicity on non-cancerous human embryonic kidney cells, respectively.

Aim: Hepatocellular carcinoma is one of the leading global epidemics. A medicinal tree, Moringa oleifera (MO), has been part of traditional treatments including cancer therapies. We investi...

HIV has been implicated in adverse birth outcomes, due to increased oxidative stress and inflammation. In addition, HIV has been reported to increase nitric oxide levels. Therefore the combined exposures to HIV and traffic-related air pollution, within South Durban, South Africa (SA), may lead to adverse birth outcomes. However, the exact mechanism is still unknown; this study aimed to identify a potential mechanism. First, the influence of HIV on oxidative and nitrosative stress markers in pregnant women was assessed. Secondly, the effect of these stress makers and exposure to oxides of nitrogen (NOx) on neonatal birthweight (BW) was evaluated. Finally, the effect HIV and traffic-related pollution exposure has on the oxidative and endoplasmic profile and epigenetic regulation of Nrf2-Keap1 pathway by miR-144 and miR-28 in pregnant women was determined. Women, in their third trimester with singleton pregnancies, who were HIV+ and HIV−, were recruited from Durban, SA. Biomarker levels of serum nitrites/nitrates (NO) and malondialdehyde (MDA) were analysed and mRNA expression levels of oxidative and endoplasmic stress response genes were assessed. Land regression modelling was performed to determine NOx exposure levels. HIV exposure during pregnancy was associated with increased NO levels. NO was shown to reduce neonatal BW. NO and MDA was found to reciprocally increase each other, with HIV differentially influencing MDA's effect on BW. HIV down-regulated miR-144 which was negatively associated with Nrf2, suggesting a potential mechanism for HIV associated chronic oxidative stress. This study proposes that NO plays a key role in neonatal BW reduction in response to HIV and traffic-related air pollution. Keywords: HIV, Oxidative stress, NO, Adverse birth outcomes, Traffic-pollution, Nrf2-Keap1 pathway

Raw ingredients of pet food are often contaminated with mycotoxins. This is a serious health problem to pets and causes emotional and economical stress to the pet owners. The aim of this study was to determine the immunotoxicity of the most common mycotoxins (aflatoxin, fumonisin, ochratoxin A and zearalenone) by examining 20 samples of extruded dry dog food found on the South African market [10 samples from standard grocery store lines (SB), 10 from premium veterinarian lines (PB)]. Pelleted dog food was subjected to extraction protocols optimized for the above mentioned mycotoxins. Dog lymphocytes were treated with the extracts (24 h incubation and final concentration 40 μg/ml) to determine cell viability, mitochondrial function, oxidative stress, and markers of cell death using spectrophotometry, luminometry and flow cytometry. Malondialdehyde, a marker of oxidative stress showed no significant difference between SB and PB, however, GSH was significantly depleted in SB extract treatments. Markers of apoptosis (phosphatidylserine externalization) and necrosis (propidium iodide incorporation) were elevated in both food lines when compared to untreated control cells, interestingly SB extracts were significantly higher than PB. We also observed decreased ATP levels and increased mitochondrial depolarization in cells treated with both lines of feed with SB showing the greatest differences when compared to the control. This study provides evidence that irrespective of price, quality or marketing channels, pet foods present a high risk of mycotoxin contamination. Though in this study PB fared better than SB in regards to cell toxicity, there is a multitude of other factors that need to be studied which may have an influence on other negative outcomes.

Highly active antiretroviral therapy has evolved over the years, leading to a boost in the quality of life in people living with HIV and AIDS. However, growing evidence has shown that highly active antiretroviral therapy has deleterious effects on the testes and the overall reproductive capacity. Therefore, this study is to determine the adjuvant potential of Naringenin on highly active antiretroviral therapy-induced perturbations in fertility of male Sprague-Dawley rats. Thirty adult male Sprague-Dawley rats were divided into six groups viz - Control; H: 30 mg/kg of highly active antiretroviral therapy (EFV, 600 mg + FTC, 200 mg + TDF, 300 mg); N40: Naringenin, 40 mg/kg; N80: Naringenin, 80 mg/kg; HN40: highly active antiretroviral therapy + Naringenin, 40 mg/kg; HN80: highly active antiretroviral therapy + Naringenin, 80 mg/kg. The rats were euthanized after 4 weeks. Results showed that there was a significant decrease in sperm count (p

Master of Medical Science in Medical Biochemistry and Chemical Pathology. University of KwaZulu-Natal, Durban 2016.

Esophageal cancer (EC) is commonly diagnosed in South Africa (SA), with high incidences occurring in SA's black population. Moringa oleifera (MO), a multipurpose tree, is used traditionally for its nutritional and medicinal properties. It has been used for the treatment of a variety of ailments, including cancer. We investigated the antiproliferative effect of MO crude aqueous leaf extract (MOE) on a cancerous esophageal cell line (SNO). SNO cells were exposed to a range of MOE dilutions to evaluate cytotoxicity (MTT assay). Oxidative stress was determined using the TBARS assay. The comet assay was used to assess DNA damage. We then determined cell death mechanisms by measuring phosphatidylserine (PS) externalization (flow cytometry), caspase-3/7 and caspase-9 activities, and adenosine triphosphate (ATP) levels (luminometry). Protein expression of Smac/DIABLO and PARP-1 was determined by western blotting. SNO cells were treated with a range of MOE dilutions to obtain an IC50 value of 389.2 μg/mL MOE (24 h), which was used in all subsequent assays. MOE significantly increased lipid peroxidation (P .05) and DNA fragmentation (P .0001) in SNO cells. The induction of apoptosis was confirmed by the increase in PS externalization (P .0001), caspase-9 (P .05) and caspase-3/7 (P = .22) activities, and decreased ATP levels (P .0001). MOE significantly increased both the expression of Smac/DIABLO protein and cleavage of PARP-1, resulting in an increase in the 24-kDa fragment (P .001). MOE possesses antiproliferative effects on SNO EC cells by increasing lipid peroxidation, DNA fragmentation, and induction of apoptosis.

Cancer is classified as one of the leading causes of global mortality. It has affected millions of people, often with poor prognosis. Having severe side-effects with conventional chemotherapy, alternate drugs and therapies are actively being investigated. There is a need for innovative drug discovery and design as existing cancer therapies are costly and not readily available. Ayurveda and traditional medicine have utilised natural resources such as plants and trees as part of their regime to treat various illness and diseases with positive outcomes. One such tree is Moringa oleifera (MO). Almost all parts have shown to be effective against several ailments including cancer which was attributed to the bioactive constituents. Targeted therapies had led to the development of nanoparticles which are extremely effective in various biomedical applications due to their small size. Green synthesis of gold nanoparticles have great potential as naturally occurring plants and trees such as MO can be used in the synthesis process. The resultant gold phytonanoparticles are useful in cancer therapies with improved survival rates and quality of life. The review highlights the importance of MO in natural medicine, synthesis of phytonanoparticles and the fundamental role as a potential antiproliferative agent against cancer.

Gold nanoparticles (AuNP's) facilitate cancer cell recognition and can be manufactured by green synthesis using nutrient rich medicinal plants such as Moringa oleifera (MO). Targeting dysregulated oncogenes and tumor suppressor genes is crucial for cancer therapeutics. We investigated the antiproliferative effects of AuNP synthesized from MO aqueous leaf extracts (MLAuNP ) in A549 lung and SNO oesophageal cancer cells. A one-pot green synthesis technique was used to synthesise MLAuNP . A549, SNO cancer cells and normal peripheral blood mononuclear cells (PBMCs) were exposed to MLAuNP and CAuNP to evaluate cytotoxicity (MTT assay); apoptosis was measured by phosphatidylserine (PS) externalization, mitochondrial depolarization (ΔΨm) (flow cytometry), caspase-3/7, -9 activity, and ATP levels (luminometry). The mRNA expression of c-myc, p53, Skp2, Fbw7α, and caspase-9 splice variants was determined using qPCR, while relative protein expression of c-myc, p53, SRp30a, Bax, Bcl-2, Smac/DIABLO, Hsp70, and PARP-1 were determined by Western blotting. MLAuNP and CAuNP were not cytotoxic to PBMCs, whilst its pro-apoptotic properties were confirmed in A549 and SNO cells. MLAuNP significantly increased caspase activity in SNO cells while MLAuNP significantly increased PS externalization, ΔΨm, caspase-9, caspase-3/7 activities, and decreased ATP levels in A549 cells. Also, p53 mRNA and protein levels, SRp30a (P = 0.428), Bax, Smac/DIABLO and PARP-1 24 kDa fragment levels were significantly increased. Conversely, MLAuNP significantly decreased Bcl-2, Hsp70, Skp2, Fbw7α, c-myc mRNA, and protein levels and activated alternate splicing with caspase-9a splice variant being significantly increased. MLAuNP possesses antiproliferative properties and induced apoptosis in A549 cells by activating alternate splicing of caspase-9. J. Cell. Biochem. 117: 2302-2314, 2016. © 2016 Wiley Periodicals, Inc.

Fusaric acid (FA), a common fungal contaminant of maize, is known to mediate toxicity in plants and animals; however, its mechanism of action is unclear. p53 is a tumor suppressor protein that is activated in response to cellular stress. The function of p53 is regulated by post-translational modifications-ubiquitination, phosphorylation, and acetylation. This study investigated a possible mechanism of FA induced toxicity in the human hepatocellular carcinoma (HepG

South Africa’s (SA’s) mortality rates are increasing due to increased cancer diagnosis. In addition, bacterial infections are on the rise with increasing antibacterial resistance. Current chemotherapies and antibacterial agents are expensive with many side-effects; therefore alternative therapies are actively being investigated. A medicinal tree, Moringa oleifera (MO), is found throughout SA and used in traditional treatment of a variety of ailments including cancer and microbial infections. All parts of the tree are used for medicinal purposes including leaves, flowers, bark, seeds and seedpods (drumstick). The use of MO extracts has been beneficial for people across many communities as a food source in addition to its medicinal properties. Nanoparticles have a wide range of biomedical applications and are showing potential as anticancer and antibacterial agents. Their relative smaller size (1–100 nm) facilitates their mode of action against diseases. Nanoparticles are synthesised chemically or via plant extracts which are environmentally friendly and less toxic. MO can be used for nanoparticle synthesis such as gold nanoparticles (AuNPs) using a one-pot green synthesis technique. Therapeutic applications of AuNPs have been assessed both in vitro and in vivo with positive outcomes. The review aims to discuss the therapeutic potential of AuNPs as anticancer and antibacterial agents.

Oesophageal cancer (OC) is a global problem incrementally incident among black South African males. The high incidence of OC may be due to the consumption of corn as a staple, often contaminated with mycotoxins. Fusaric acid (FA), a neglected mycotoxin, is known to disrupt mitochondrial energy metabolism, chelates divalent metal cations and induces cell death in plants. This study investigated FA-induced cytotoxicity and apoptotic induction in the SNO OC cell line. Cells were treated with FA (IC50 = 78.81 μg/mL; 24 h; MTT assay) and assayed for oxidative stress and membrane damage (TBARS, LDH cytotoxicity and glutathione), apoptotic induction (ATP levels, caspase-8, -9, -3/7 activities) (Luminometry), single strand DNA and nuclear fragmentation (Comet and Hoechst assay). Additionally, relative expression of pro- and anti-apoptotic proteins were determined (Western Blotting). Significant antioxidant depletion was consistent with a concomitant increase in ROS-induced lipid peroxidation and extracellular LDH levels. FA induced apoptosis by significantly increasing Bax expression and caspase-8, -9 and -3/7 activities whilst decreasing ATP levels and Bcl-2 expression. Further, FA significantly increased comet tail lengths, PARP-1 expression and late stage apoptotic body formation in SNO cells. This study shows that FA is cytotoxic and induces increased apoptosis in SNO cells.

Background Petrol attendants are at risk for the development of cancers. Exposures experienced by such workers include polycyclic aromatic hydrocarbons PAH’s and the volatile organic compounds (VOCs) which are associated with DNA damage, DNA strand breaks, micronuclei and chromosomal aberrations. Aim To determine the effect of petrol exposure on DNA integrity in peripheral blood lymphocytes among petrol attendants and a non-exposed comparison population. Methods Fuel station employees (n = 101) and office-based non-exposed (n = 50) workers in Durban, South Africa were interviewed using a validated questionnaire. Genomic DNA was extracted from peripheral lymphocytes for the benzo(a)pyrene diol epoxide (BPDE)-DNA Adduct assay (ELISA), and DNA damage was determined using the comet assay. Results Among the exposed, the mean duration of employment in the fuel industry was 5.8 years (SD = 4.6) and among those pumping fuel (n = 75), the mean metric tons of petrol pumped in the past 12 months per worker was 199.2 (SD = 88.9). The mean percentage tail DNA varied significantly between exposed and non-exposed groups: 23.8% (SD = 13.3) and 8.1% (SD = 1.8) (p Conclusion Our study adds to the literature that long term, low dose exposure to vehicular fuels are likely to result in altered DNA integrity and genotoxicity among petrol attendants. These results strengthen the case that these workers must be afforded appropriate protection to prevent serious adverse outcomes.

The biosynthesis of nanostructured biopalladium nanoparticles (PdNPs) from an aqueous solution of crystalline palladium acetate is reported. For the synthesised PdNPs in solution, an agroforest biomass waste petal of Moringa oleifera derived bis-phthalate was used as natural reducing and biocapping agents. Continuous absorption in the UV region and subsequent brown colour change confirmed the formation of PdNPs. A strong surface plasmon peak for PdNPs occurred at 460nm. PdNPs were characterized by SEM with EDX, FTIR, TEM and DLS. The chemical composition of the aqueous extract was determined by GC-MS coupled with FTIR and 1NMR. The catalytic degradation effect by PdNPs on industrial organic toxic effluents p-nitrophenol (PNP) and methylene blue dye was monitored by UV Spectroscopy. On the other hand PdNPs catalysed the base mediated suzuki coupling reaction for biphenyl synthesis, in water. Moreover, PdNPs were found to be reusable catalysts. Toxicity studies of PdNPs showed that the death of brine shrimp to be

Cancer is a leading cause of death in South Africa (SA). Nanoparticles (NPs) have potential uses in cancer therapies due to their size (1–100 nm). Nanoparticles are stabilized chemically or via the use of plants. Moringa oleifera (MO), found widely in SA, possesses medicinal properties with MO leaves (MOE) and flowers (MF) with high nutritional value. MOE and MF can be utilized in the synthesis of gold nanoparticles (AuNPs). Apoptosis maintains homeostasis and disruptions to this lead to cancer pathogenesis. Oncogenes encourage tumor progression and dysregulation by tumor suppressor genes ensures that abnormal cells continue in the cell cycle. They are often resistant to chemotherapy. The review aims to present and discuss the potential of AuNPs as a chemotherapeutic agent in targeting oncogenes and tumor suppressor genes with negligible effects on normal cells. Furthermore, the synthesis (one-pot green synthesis technique) of these novel nanoparticles can be beneficial for cancer therapies.

Gold nanoparticles (AuNP's) facilitate cancer cell recognition and can be manufactured by green synthesis using nutrient rich medicinal plants such as Moringa oleifera (MO). Targeting dysregulated oncogenes and tumor suppressor genes is crucial for cancer therapeutics. We investigated the antiproliferative effects of AuNP synthesized from MO aqueous leaf extracts (MLAuNP ) in A549 lung and SNO oesophageal cancer cells. A one-pot green synthesis technique was used to synthesise MLAuNP . A549, SNO cancer cells and normal peripheral blood mononuclear cells (PBMCs) were exposed to MLAuNP and CAuNP to evaluate cytotoxicity (MTT assay); apoptosis was measured by phosphatidylserine (PS) externalization, mitochondrial depolarization (ΔΨm) (flow cytometry), caspase-3/7, -9 activity, and ATP levels (luminometry). The mRNA expression of c-myc, p53, Skp2, Fbw7α, and caspase-9 splice variants was determined using qPCR, while relative protein expression of c-myc, p53, SRp30a, Bax, Bcl-2, Smac/DIABLO, Hsp70, and PARP-1 were determined by Western blotting. MLAuNP and CAuNP were not cytotoxic to PBMCs, whilst its pro-apoptotic properties were confirmed in A549 and SNO cells. MLAuNP significantly increased caspase activity in SNO cells while MLAuNP significantly increased PS externalization, ΔΨm, caspase-9, caspase-3/7 activities, and decreased ATP levels in A549 cells. Also, p53 mRNA and protein levels, SRp30a (P = 0.428), Bax, Smac/DIABLO and PARP-1 24 kDa fragment levels were significantly increased. Conversely, MLAuNP significantly decreased Bcl-2, Hsp70, Skp2, Fbw7α, c-myc mRNA, and protein levels and activated alternate splicing with caspase-9a splice variant being significantly increased. MLAuNP possesses antiproliferative properties and induced apoptosis in A549 cells by activating alternate splicing of caspase-9. J. Cell. Biochem. 117: 2302-2314, 2016. © 2016 Wiley Periodicals, Inc.

To determine the effect of petrol exposure on DNA integrity in peripheral blood lymphocytes among petrol attendants and a non-exposed comparison population. This cross-sectional study included 101 fuel station employees and 50 office-based non-exposed workers in Durban, South Africa. Participants were interviewed using a validated questionnaire. Genomic DNA was extracted from peripheral lymphocytes for the benzo(a)pyrene diol epoxide (BPDE)-DNA adduct assay (ELISA), and DNA damage was determined using the comet assay and reported as percentage tail DNA. The exposed (n = 101) and non-exposed participants (n = 50) varied with regard to age, housing, smoking, and proximity to industry and petrol stations. Among the exposed, the mean duration of employment in the fuel industry was 5.8 years (SD = 4.6), and among those pumping fuel (n = 75), the mean metric tons of petrol pumped in the past 12 months per worker was 199.2 (SD = 88.9). The mean percentage tail DNA varied significantly between exposed and non-exposed groups: 23.8 % (SD = 13.3) and 8.1 % (SD = 1.8) (p

Background The incidence of lung cancer is expected to increase due to increases in exposure to airborne pollutants and cigarette smoke. Moringa oleifera (MO), a medicinal plant found mainly in Asia and South Africa is used in the traditional treatment of various ailments including cancer. This study investigated the antiproliferative effect of MO leaf extract (MOE) in cancerous A549 lung cells. Methods A crude aqueous leaf extract was prepared and the cells were treated with 166.7 μg/ml MOE (IC50) for 24 h and assayed for oxidative stress (TBARS and Glutathione assays), DNA fragmentation (comet assay) and caspase (3/7 and 9) activity. In addition, the expression of Nrf2, p53, Smac/DIABLO and PARP-1 was determined by Western blotting. The mRNA expression of Nrf2 and p53 was assessed using qPCR. Results A significant increase in reactive oxygen species with a concomitant decrease in intracellular glutathione levels (p p p p p p Conclusion MOE exerts antiproliferative effects in A549 lung cells by increasing oxidative stress, DNA fragmentation and inducing apoptosis.