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1.
Nutr Cancer ; 74(1): 288-298, 2022.
Article in English | MEDLINE | ID: mdl-33511885

ABSTRACT

The present study was undertaken to evaluate the chemopreventive activity of myrtenal, a natural monoterpene, against bladder carcinoma in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and promoted with γ-ionizing radiation (γ-IRR) as well as to assess the involvement of inflammation, apoptosis and oxidative damage in tumor development. Histopathological examination of rat bladder revealed the presence of noninvasive papillary transitional cell carcinoma (Grade 2) in sections from BBN group indicating the credibility of the applied carcinogenesis model. Myrtenal treatment caused improvement in urinary bladder mucosa with cells more likely in Grade 1. Administration of myrtenal to BBN-treated rats exhibited downregulation in the expressions of COX-2, NF-kB and STAT-3 associated with suppression of inflammatory cytokines levels of TNF-α and IL-6 as well as biomarkers of oxidative damage (MDA & NO). In addition, myrtenal treatment caused a significant increase in caspase-3 activity and Bax/Bcl-2 ratio. Data obtained suggested that the anti-inflammatory effect and the induction of apoptosis contributed largely to the beneficial antitumor effects of myrtenal in rats with BBN/γ-IRR-induced bladder carcinoma. Present findings, in addition to benefits described in other pathologies, indicated myrtenal as a potential adjuvant natural compound for the prevention of tumor progression of bladder cancer.


Subject(s)
Nitrosamines , Urinary Bladder Neoplasms , Animals , Bicyclic Monoterpenes , Butylhydroxybutylnitrosamine/metabolism , Butylhydroxybutylnitrosamine/toxicity , Carcinogenesis , Carcinogens/pharmacology , Nitrosamines/pharmacology , Rats , Urinary Bladder/metabolism , Urinary Bladder/pathology , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/prevention & control
2.
Asian Pac J Cancer Prev ; 20(11): 3369-3376, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31759361

ABSTRACT

Gold nanoparticles are the most promising candidate in cancer treatment due to their physiochemical properties
and increased use in photothermal therapy (PTT). In the present study, spherical gold nanoparticles (AuNPs) were
synthesized using citrate reduction method. The particles were then characterized using UV-VIS spectroscopy and
transmission electron microscope. A hepatocellular carcinoma cell line (HepG2) was incubated with sorafenib and/or
non-irradiated or laser-irradiated AuNPs for 48 hrs. The cytotoxic effect of different treatment modalities was determined
using MTT assay. Furthermore, apoptosis was determined by flow cytometry using annexin V/propidium iodide, as
well as estimating the level of caspases. Results showed that AuNPs and sorafenib reduced HepG2 cell viability, and
the cytotoxicity was associated with increased release of LDH in the culture medium. The recorded cytotoxicity was
attributed to enhanced apoptosis as revealed by increased cellular caspases (3, 8 and 9), that was further confirmed by
flow cytometry. The most notable cytotoxic effect was recorded when combining sorafenib with laser-irradiated AuNPs.
In conclusion, a synergistic cytotoxic effect was observed between sorafenib and laser-irradiated AuNPs against the
growth of HepG2, suggesting the potential substitution of large toxic doses of sorafenib by lower doses in combination
with photothermal therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Proliferation/drug effects , Gold/administration & dosage , Liver Neoplasms/drug therapy , Metal Nanoparticles/administration & dosage , Sorafenib/pharmacology , Apoptosis/drug effects , Carcinoma, Hepatocellular/metabolism , Caspases/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Drug Synergism , Hep G2 Cells , Humans , Liver Neoplasms/metabolism
3.
J Diet Suppl ; 15(6): 923-938, 2018 Nov 02.
Article in English | MEDLINE | ID: mdl-29336631

ABSTRACT

Radiation protection research receives intense focus due to its significant impact on human health. The present study was undertaken to investigate the protective effect of pretreatment with tomato seed oil (TSO) against gamma radiation-induced damage in rats. Male Wistar rats were divided into four groups: (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO-pretreated and gamma-irradiated. Acute exposure of animals to a single gamma radiation dose (6 Gy) induced oxidative stress in major body organs, altered serum lipid homeostasis, significantly increased serum testosterone and sorbitol dehydrogenase levels, and elicited a systemic inflammation as manifested by the induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected rats against ionizing radiation-induced oxidative stress, restored lipid homeostasis, and suppressed systemic inflammation. Histological findings of target tissues verified biochemical data. The radioprotective ability of TSO was attributed to its content of phytosterols, policosanol, and antioxidants, including lycopene, ß-carotene, lutein, and tocopherols. TSO is considered a promising radioprotective agent that can be effectively used to protect the body from the damaging effects of harmful radiation.


Subject(s)
Gamma Rays/adverse effects , Plant Oils/administration & dosage , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents , Seeds/chemistry , Solanum lycopersicum , Animals , Antioxidants/pharmacology , Inflammation , Kidney/drug effects , Kidney/pathology , L-Iditol 2-Dehydrogenase/blood , Lipid Peroxidation/drug effects , Lipids/blood , Liver/drug effects , Liver/enzymology , Liver/pathology , Male , Oxidative Stress , Rats , Rats, Wistar , Superoxide Dismutase/metabolism , Testis/drug effects , Testis/pathology , Testosterone/blood , Vascular Cell Adhesion Molecule-1/blood
4.
Int J Biol Macromol ; 107(Pt B): 2342-2350, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29055707

ABSTRACT

Tannase is considered one of the most important industrial enzymes that find great applications in various sectors. Production of tannases through solid state fermentation (SSF) using agro-industrial wastes is an eco-friendly and cheap technology. Tannase was produced by the yeast Kluyveromyces marxianus using olive pomace as a solid support under SSF. It was purified using ammonium sulfate fractional precipitation followed by Sephadex G-200 gel filtration resulting in 64.6% enzyme yield with 1026.12U/mg specific activity and 24.21 purification fold. Pure tannase had molecular weight of 65 KDa and 66.62 KDa by SDS-PAGE and gel filtration, respectively. It showed a maximal activity at 35°C having two different pH optima, one of which is acidic (4.5) and the other one is alkaline (8.5). The enzyme was stable in the acidic range of pH (4.0-5.5) for 30min, and thermostable within the temperature range 30-70°C. Using tannic acid, the enzyme had a Km value of 0.77mM and Vmax of 263.20µmolemin-1ml-1. The effect of different metal ions on enzymatic activity was evaluated. HPLC analysis data indicated that the purified enzyme could carry out 24.65% tannic acid conversion with 5.25 folds increase in gallic acid concentration within 30min only.


Subject(s)
Carboxylic Ester Hydrolases/chemistry , Gallic Acid/chemistry , Kluyveromyces/enzymology , Ammonium Sulfate/chemistry , Carboxylic Ester Hydrolases/genetics , Carboxylic Ester Hydrolases/isolation & purification , Chromatography, High Pressure Liquid , Fermentation , Gallic Acid/metabolism , Olea/chemistry
5.
Biomed Pharmacother ; 93: 837-851, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28715867

ABSTRACT

Alzheimer's disease (AD) is a grave and prevailing neurodegenerative disease, characterized by slow and progressive neurodegeneration in different brain regions. Aluminum (Al) is a potent and widely distributed neurotoxic metal, implicated in the neuropathogenesis of AD. This study aimed to evaluate the possible neurorestorative potential of Vitis vinifera Leaves Polyphenolic (VLP) extract in alleviating aluminum chloride (AlCl3)-induced neurotoxicity in male rats. AlCl3 neurotoxicity induced a significant decrease in brain/serum acetylcholine (ACh) contents and serum dopamine (DA) levels, along with a significant increment of brain/serum acetylcholinesterase (AChE) activities. In addition, Al treatment resulted in significantly decreased serum levels of both total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF), and significantly increased serum levels of both interleukin-6 (IL-6) and total homocysteine (tHcy), as compared to control. Behavioral alterations, assessed by the T-maze test, showed impaired cognitive function. Furthermore, AD-brains revealed an increase in DNA fragmentation as evidenced by comet assay. AlCl3 induction also caused histopathological alterations in AD-brain. Treatment of AD-rats with VLP extract (100mg/kg body weight/day) improved neurobehavioral changes, as evidenced by the improvement in brain function, as well as, modulation of most biochemical markers, and confirmed by T-maze test, the histopathological study of the brain and comet assay. The current work indicates that the VLP extract has neuroprotective, antioxidative, anti-inflammatory, and anti-amnesic activities against AlCl3-induced cerebral damages and neurocognitive dysfunction.


Subject(s)
Alzheimer Disease/drug therapy , Biomarkers/metabolism , Plant Extracts/pharmacology , Polyphenols/pharmacology , Vitis/chemistry , Acetylcholinesterase/metabolism , Aluminum Chloride , Aluminum Compounds/pharmacology , Alzheimer Disease/metabolism , Animals , Antioxidants/metabolism , Brain/drug effects , Brain/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Chlorides/pharmacology , Cognition/drug effects , Homocysteine/metabolism , Interleukin-6/metabolism , Male , Neuroprotective Agents/pharmacology , Plant Leaves/chemistry , Rats , Rats, Wistar
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