Analysis and risk assessment of pharmaceutical residues in fish from three water bodies in Ghana.

Illegal mining has overshadowed pharmaceutical pollution even though exposure to pharmaceutical waste is high. Consumption of fish potentially polluted with pharmaceuticals from the rivers continues with little concern or potential threat it poses. In the present study, the residues of one antibiotic (Chloramphenicol), five hormones (progesterone, 17-beta Estradiol, Estrone, 17a-Ethynylestradiol, and one), three environmental contaminants (4-para-nonylphenol, 4-tert-octylphenol, and Bisphenol A), one barbiturate (Primidone) and one analgesic (Diclofenac sodium salt), were investigated from fish samples from the rivers Pra, Narkwa, and the Volta. The results show a high concentration of drugs in River Pra in comparison to those in Rivers Narkwa and Volta. The hazard quotients (HQs) for the environmental contaminants were all above 1, except Bisphenol A. Furthermore, the HQs from this study suggest that consumers of fish from any of the three rivers stand a hazard risk of Chloramphenicol (19), 17a-Ethynylestradiol (4), Estrone (1.366), Diclofenac sodium salt (3.29), Progesterone (4.598), 4-tert-octylphenol (87.2), and 4-para-nonylphenol (7.252), but negligible risk against E2 (0.687), Primidone (0.014), Testosterone (0.16), and Bisphenol A (0.642). Of the fish species studied, the highest concentration of all pharmaceuticals put together is found in Clarias gariepinus, Labeo senegalensis, and Chrysichthys nigrodigitatus in that order.

Glyco disulfide capped gold nanoparticle synthesis: cytotoxicity studies and effects on lung cancer A549 cells.

Background: Glyco disulfide gold nanoparticles (GDAuNPs) were prepared by three methods: direct, photochemical irradiation and ligand substitution. Glyco disulfide acted as reducing and capping agents of gold ions, to produce AuNPs GD1-GD16. Results: Shorter chains of glyco disulfides (n = 1 and 2) offered monodispersed and stable GDAuNPs in physiological pH, while longer chains (n = 3) furnished unstable nanoparticles. ζ-potential study of direct method GDAuNPs revealed surface charge dependency on the alkyl unit length. Transmission electron microscope imaging indicated that sizes/shapes of the ligand exchange AuNPs remained post-exchange step. The mechanism of GDAuNP formation was forecast as the Ostwald ripening effect at low pH of ligand (5.1-8.9) and reinforcement of static stabilization at high pH (12.4-13.0). Conclusion: GDAuNPs recorded moderately anticancer activity against the A549 cancer cell line, with IC50 between 14.95 and 64.95 µg/ml.

Allanblackia floribunda Seed Extract Attenuates the Ethanol-Induced Gastric Ulcer in Rats via the Inhibition of TNF-α and INF-γ Levels and Modulation in the Expression of Ki67 Protein.

Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance (p < 0.001) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses.

Structural elucidation and in vivo anti-arthritic activity of ß-amyrin and polpunonic acid isolated from the root bark of Ziziphus abyssinica HochstEx. A Rich (Rhamnaceae).

Two natural products, compounds 1 and 2 were isolated from the root bark of Ziziphus abyssinica for the first time and were structurally elucidated as ß-amyrin and polpunonic acid, respectively. Both compounds were further subjected to an in vivo study in rats to evaluate their anti-arthritic potency. Compared to the arthritic control group, rats treated with different doses of 1 or 2 (3, 10, and 30 mg/kg) exhibited significantly higher total change in body weight as well as lower arthritic scores and total change in paw edema and erythema. Histopathological examinations of the hind paws of the rats further demonstrated the beneficial effects of both compounds as they significantly reversed cartilage erosion, subchondral cyst, and Weichselbaum's lacunae formation. Evidence of bone remodeling was also observed in all groups of rats treated with 1 or 2. Hematological and serum biochemical parameters were not significantly affected by treatment of 1 or 2. Taken together, the results from the present study suggest potential therapeutic benefit of ß-amyrin and polpunonic acid in rheumatoid arthritis and related inflammatory disorders.

Development and characterization of functionalized glyco thiolate capped gold nanoparticles for biological applications.

Glyco-gold nanoparticles (AuNPs) in aqueous dispersions were prepared by two approaches, namely direct reduction and ligand substitution methods. In the direct method, potassium salts of glyco thiols, with the general formula (C6H11O6)NH(CH2) n CH2SK (where L1, n = 1; L2, n = 2; L3, n = 3, L4, n = 4; L5, n = 5), were used as reducing and capping agents to give the glyco thiolate capped gold nanoparticles (AuNPs G1-G5); meanwhile in the ligand exchange experiments, L1-L5 and their acetylated forms (L6-L8) replaced citrate ions in citrate-capped gold nanoparticles to give additional AuNPs G6-G11. UV-visible spectroscopy, surface charge (ζ-potential,) measurements and transmission electron microscopy (TEM) were used for physical and chemical characterization of all the resultant AuNPs. The ζ-potential studies of AuNPs prepared through the direct method revealed that the surface charge is dependent on the length of the alkyl unit of (C6H11O6)NH(CH2) n CH2S- ligands. TEM images of the acetylated and non-acetylated glyco thiolate capped gold nanoparticles (AuNPs G6-G11) prepared via the ligand exchange method indicate that the size and shape of the gold nanoparticles remained the same as those of the citrate-capped gold nanoparticles used to prepare them. Selected AuNPs were tested on peripheral blood mononuclear cells (PBMCs) and the A549 cancer cell line to investigate their respective toxicity and cytotoxicity profiles. All AuNPs showed indiscriminate activity against both PBMCs and A4549 cells, although the gold nanoparticles having an acetylated glyco moiety with an amino propyl thiol linker as the ligand (G10) prepared via the citrate exchange method had better selectivity (PBMCs >59 mg mL-1 and for A549 ∼7 µg mL-1).

Therapeutic potential of dithiocarbamate supported gold compounds.

Chrysotherapy or aurotherapy, the use of gold as medicine, is two thousand years old. Hitherto, numerous diverse gold stabilizing ligands for instance vitamins, pyridine, phosphines, naphthylamine and xanthanes have been developed and their 'chelating effect' in addition to their anti-proliferative properties have been extensively studied. Recent advances in the field of bioinorganic chemistry have led to the design of biologically relevant metal complexes with appropriate fine-tuned ligands such as metallic conjugates of dithiocarbamates (DTCs). DTC compounds have been recognised to possess diverse applications and have demonstrated interesting biological properties. For instance, the chemoprotective and antitumour properties of gold metal ions and DTC compounds respectively, presents an innovative and effective approach to cancer management. This review presents therefore the therapeutic potential of DTC ligand systems as a support for gold compounds. The importance of dithiocarbamate supported gold compounds as potential therapeutic agents is highlighted with emphasis on the therapeutic potential of gold(iii) and gold(i) dithiocarbamate derivatives.

Histoprotective Effect of Essential Oil from Citrus aurantifolia in Testosterone-Induced Benign Prostatic Hyperplasia Rat.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urological disorder reported among ageing men. OBJECTIVE: The study assessed histoprotective effect of lime essential oil (LEO) in a rat model of testosterone-induced benign prostatic hyperplasia (BPH) and evaluated its ability to reverse testosterone-mediated changes in the testis, kidney, and liver. MATERIALS AND METHODS: Adult Sprague Dawley (aged 12 weeks, 240-390 g) male rats were intramuscularly injected with testosterone enanthate (TE) (10 mg/kg) reconstituted in olive oil for ten days to establish benign prostatic hyperplasia (serum PSA level ≥ 1.24 ng/ml) in. After confirmation of BPH (sustained serum PSA level ≥ 1.24 ng/ml), rats in all groups (LEO: 30, 100, and 300 mg/kg, po, n = 6; finasteride: 15 mg/kg, po, n = 6) except model (BPH without treatment) and sham (no BPH and no treatment) groups were treated for 21 days. At the end of treatment, rats were anesthetised and blood was collected via cardiac puncture to determine serum PSA and total antioxidant capacity (TAC) levels. The prostate gland, testis, kidney, and liver were harvested, weighed, histologically processed and stained with H&E. RESULTS: LEO- and finasteride-treated groups recorded lesser mean prostatic weights relative to their model group. Baseline mean serum PSA level of LEO- and finasteride-treated groups reduced significantly (p < 0.05) relative to model group. Serum TAC levels were also higher in LEO- and finasteride-treated groups relative to model group. LEO-treated groups had less thickened glandular epithelium, smaller acini, fewer prostatic secretions and more fibromuscular stroma relative to model group. LEO and finasteride treatment produced improved histomorphological characteristics of testis, kidney, and liver compared to model group. CONCLUSION: By the current results, Citrus aurantifolia LEO may possess active agents that can be explored for translational medicine against BPH.

Chemical profile and in vivo toxicity evaluation of unripe Citrus aurantifolia essential oil.

Citrus aurantifolia (Christm.) Swingle (syn. C. MEDICA var. ACIDA Brandis) (family: Rutaceae) essential oil is one of the cheapest oils found in local markets. Although, it is generally accepted as non-toxic to vital organs and cells, majority of people are cynical about it usage. Herein, the present study reports the chemical composition and in vivo oral toxicity study of unripe C. aurantifolia essential oil found in Ghana. The toxicity of C. aurantifolia essential oil extract was investigated via oral administration using two methods: The acute toxicity single dose study (SDS) and the repeated dose method. The oil exhibited no acute toxicity but in the sub-chronic studies, the effects was dose and time-dependent. Chemical profile investigation of the oil showed 9 constituent of phytochemicals (Germacrene isomers (61.2%), Pineen (14%), Linalool dimmer (2.9%), Bornane (11%), Citral (2.9%), Anethole (1.5%), Anisole (1.1%), Safrole (0.3%) and Demitol (0.6%)). Histopathological studies revealed conditions such as necrosis, edema and inflammatory reaction in the liver, spleen and kidneys. Marginal upsurge of biochemical parameters above normal and elevated levels of lymphocytes (35.20-46.40 g/dL) demonstrated mild toxicity among the 100 mg/kg and 500 mg/kg dose groups at the sub-chronic stage. Low levels of hemoglobin (13.60 to 12.70 g/dL), MCV (34.20-24.0 fL), MCH (40.20-36.40 g/dL) along with high levels of liver enzymes confirmed the mild toxicity of the oil at sub-chronic stage. These results demonstrate that, despite consideration of lime essential oil as safe, it can have mild hematotoxic, nephrotoxic and hepatotoxic effects.

Immunotherapy for acute myeloid leukemia (AML): a potent alternative therapy.

The standard therapy of AML for many years has been chemotherapy with or without stem transplantation. However, there has not been any tangible improvement in this treatment beyond induction through chemotherapy and consolidation with allogeneic stem cell transplantation or chemotherapy. Residual AML cells which later cause relapse mostly persist even after rigorous standard therapy. It is imperative therefore to find an alternative therapy that can take care of the residual AML cells. With a better understanding of how the immune system works to destroy tumor cells and inhibit their growth, another therapeutic option immunotherapy has emerged to address the difficulties associated with the standard therapy. Identification of leukemia-associated antigens (LAA) and the fact that T and NK cells can be activated to exert cytotoxicity on AML cells have further introduced diverse immunotherapeutic development strategies. This review discusses the merits of current immunotherapeutic strategies such as the use of antibodies, adoptive T cells and alloreactive NK cell, and vaccination as against the standard therapy of AML.

Bispecific Antibodies (bsAbs): Promising Immunotherapeutic Agents for Cancer Therapy.

Antibodies have become the preferred therapeutic treatment option for cancers. Antibody therapy is associated with low toxic profile and specific in its activity, unlike chemotherapy and radiotherapy. Types of tumor are known to express multiple receptors that cross-talk to activate perpetual growth, proliferation and metastasis, and inhibit apoptosis in such tumors. Bispecific antibodies (BsAbs) are therefore the preferred agent for the treatment of such cancers due to its unique characteristics. This review discusses up to date therapeutic potentials of BsAbs.

Synthetic Approach to Glycopolymer Base Nanoparticle Gold(I) Conjugate: A New Generation of Therapeutic Agents.

Advances in nanotechnology have led to the fabrication of nano-constructs of organic or inorganic origins with well-defined structures, surface properties, and can be made to respond to physical or chemical stimuli. These nano-constructs can provide a shift in the way diagnostic and therapeutic drugs are delivered to achieve target specificity and increased retention of therapeutic doses for considerable improvement in the overall treatment of the tumors. In this case we describe here a synthetic approach to glycopolymer base nanoparticle gold(I) conjugate for cancer therapy.

Synthesis and evaluation of glycopolymeric decorated gold nanoparticles functionalized with gold-triphenyl phosphine as anti-cancer agents.

In this study, statistical glyco-dithiocarbamate (DTC) copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently used to prepare glyconanoparticles and conjugated glyconanoparticles with the anticancer drug, gold(I) triphenylphosphine. These glyconanoparticles and the corresponding conjugates were then tested for their in vitro cytotoxicity in both normal and cancer cell lines using Neutral Red assay. The glyconanoparticles and their Au(I)PPh3 conjugates were all active against MCF7 and HepG2 cells, but galactose-functionalized glyconanoparticles {P(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP} were found to be the most cytotoxic to HepG2 cells (IC50 ∼ 4.13 ± 0.73 µg/mL). The p(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP was found to be a 4-fold more potent antitumor agent in HepG2 cells, and the overexpressed asialoglycoprotein (ASGPR) receptors revealed to play an important role in the cytotoxicity, presumably by the enhanced uptake. In addition, the glyconanoparticles Au(I) conjugates are found to be significantly more toxic as compared to the standard chemotherapeutic reagents such as cisplatin and cytarabine.