Thioacetamide (TAA) is a potent hepatotoxin that causes centrilobulal necrosis and nephrotoxic damage following acute administration. Prolonged exposure to TAA can result in bile duct proliferation and liver cirrhosis histologically similar to that caused due to viral hepatitis infection. Coriander in food increases the antioxidant content, acting as a natural antioxidant and inhibiting undesirable oxidation processes. The present study investigated the antioxidant activity of Coriandrum sativum on TAA-induced hepatotoxicity in the male rats. Phenolic content and antioxidant activity were evaluated in the coriander leaves and seeds. Forty-eight adult male rats were divided into four groups. Group I (control), group II (TAA injected rats), group III (TAA injected rats fed coriander leaves) and group IV (TAA injected rats fed coriander seeds). The results revealed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were significantly increased in the groups II, III and IV as compared to the normal control. Oxidative stress in the group II was manifested by a significant rise in nitric oxide (NO), thiobarbituric acid reactive substance (TBARS) levels and myloperoxidase (MPO) activities in the liver tissues as compared with the control group. Rats fed with coriander leaves and seeds showed a decrease in the serum ALT, AST and ALP activities and in the liver NO and TBARS levels as compared to the group II. Histopathological study revealed that coriander feeding attenuated TAA-induced hepatotoxicity in the rats. In conclusion, coriander leaves attenuate hepatotoxicity induced by TAA more than that of seeds due to the higher content of phenolic compounds and antioxidants in the leaves of coriander. Liver of rats intoxicated with TAA exhibited advanced CIRRHOSIS: in the form of macronodular and micronodular structure surrounded by fibrous tissue. Treatment with coriander leaves and seeds helps in improving the adverse effect of TAA-induced hepatotoxicity; also the histological study confirms this finding.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1β, interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.

BackgroundTitanium dioxide nanoparticles (TiO2 NPs) are widely used in the biological sciences. The increasing use of TiO2 NPs increases the risk of humans and the environment being exposed to NPs. We previously showed that toll-like receptors (TLRs) play an important role in the interactions between NPs and cells. Our previous results indicated that TLR4 increased the DNA damage response induced by TiO2 NPs, due to enhanced NP uptake into the cytoplasm, whereas TLR3 expression decreased the DNA damage response induced by TiO2 NPs because of NP retention in the endosome. In this study, we explored the molecular mechanism of the DNA damage response induced by TiO2 NPs using TLR3 or TLR4 transfected cells. We examined the effect of TLR3 or TLR4 over-expression on oxidative stress and the effect of DNA damage induced by TiO2 NPs on gene expression levels.ResultsOur results showed evidence for elevated oxidative stress, including the generation of reactive oxygen species (ROS), with increased hydrogen peroxide levels, decreased glutathione peroxidase, and reduced glutathione and activated caspase-3 levels in cells exposed for 48 h to 10 μg/ml TiO2 NPs. These effects were enhanced by TLR4 and reduced by TLR3 over-expression. Seventeen genes related to DNA double-strand breaks and apoptosis were induced, particularly IP6K3 and ATM.ConclusionOur results indicated that TiO2 NPs induced ROS, and the above molecules are implicated in the genotoxicity induced by TiO2 NPs.

In a recent study, the treatment of different human cancer cell lines in vitro with ethylene diamine tetra-acetic acid (EDTA) showed a promising anticancer activity which could be a novel promising approach for cancer treatment. The aim of this study is to address the ability of EDTA to enhance the antitumor efficacy of the low dose of cisplatin (Cis) treatment in Ehrlich ascetic carcinoma (EAC) bearing mice. Sixty female albino mice were divided into six groups. The 1 st group of mice was served as a negative control. 2 nd -6 th groups were inoculated intraperitoneal (i.p) with 2×10 6 EAC cells/mouse. After one day of inoculation, the 2 nd , 3 rd and 4 th groups were injected daily for 6 days (early treatment) with phosphate buffer saline, low dose of Cis and Cis/EDTA, respectively. After six days, the 5 th and 6 th groups were injected with the low dose of Cis and Cis/EDTA for 6 consecutive days (late treatment), respectively. At day 14, all groups of mice were sacrificed, sera were collected for biochemical assessment, HIGHLIGHTS• EDTA enhanced the antitumor efficacy of the low dose of Cisplatin.• Low dose of Cisplatin did not inhibit tumor growth • Co-treatment with EDTA delayed and decreased tumor growth.• EDTA decreased the toxicity of Cisplatin. 2 El-Naggar, S.A.; et al.

Background: Several studies have found an association between Diabetes mellitus (DM) and an increased risk for hepatocellular carcinoma (HCC). Evidence suggests that Metformin (Met) may have a therapeutic and protective effect against both DM and HCC. Therefore, the aim of this study was to evaluate the antioxidant effect of Met against DM and HCC-induced oxidative stress in rat model. Methods: Forty-two male albino rats were randomly divided into six groups. Group 1 (Gp1) was the control group, Gp2 received an intraperitoneal (i.p.) injection with streptozotocin (STZ), Gp3 was injected i.p. with diethyl nitrosamine (DEN), Gp4 received an oral administration of Met, Gp5 and Gp6 received the same injections as Gp2 and Gp3, respectively, then received an additional injection of Met. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and malondialdehyde (MDA), were examined. Furthermore, biochemical parameters including liver function tests were assessed. Histopathological and immunohistochemical alterations of the liver were also examined. Results: Our results demonstrate that Gp2 and Gp3 had significant signs of liver dysfunction and had elevated levels of MDA and reduced levels of SOD, CAT, and GSH. Additionally, Gp2 and Gp3 showed significant alterations in the liver architecture shown by high PCNA and caspase-3 expression. In the Gp5 and Gp6, treatment with Met showed an improvement in liver function, oxidative stress biomarkers, and reduced histopathological changes in hepatocytes. Conclusions: This study offers insight into the potential for Metformin as a novel therapeutic against the oxidative stress induced by DM or HCC.

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High-molecular-weight poly(3-hydroxybutyrate) (PHB) has a low reactivity toward its terminal functional groups. Thus, the chemical reactivity of PHB was enhanced by the chemical degradation that occurred via β-elimination through the functionalization of PHB with ethylene glycol to give a low-molecular-weight PHB-diol. The reaction of PHB-diol with acryloyl chloride gave PHB-diacrylate, which was grafted by thiol compounds, such as ethane dithiol, 2-mercaptoethanol, ethane thiol, dithiothreitol, butane thiol, and thioglycolic acid, via a Michael-type addition reaction. The chemical and thermal properties of the functionalized PHB-thiol products were characterized with Fourier transform infrared spectroscopy, 1 H-NMR, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis techniques. X-ray diffraction showed that the PHB-thiol polymers had slight differences in crystallinity compared with neat PHB. The biological activities of the neat polymer and new PHB-thiol polymers, including the antibacterial and anticancer activities, were tested, and some of these products showed antibacterial and anticancer activities. These anticancer activities were attributed to the ability of these PHB-thiol polymers to induce apoptosis (as revealed by the higher expression of Bax and caspase 9 and the lower expression of Bcl2) and cell-cycle arrest in the G0/G1 phase, which is associated with the higher expression of p53 and p21 and the lower expression of the p53 inhibitor, MDM2. Thus, the anticancer effect of these PHB-thiol polymers may have been due to their ability to inhibit MDM2-p53 interactions.

Ethylenediamine tetraacetic acid (EDTA) is used in various medical applications. The aim of this study is to investigate the antitumor efficacy of EDTA alone or with cisplatin (Cis). Fifty male albino mice were used to assess the median lethal dose (LD 50) of EDTA via intraperitoneal (i.p) injection. To determine the antitumor activity, fifty female albino mice were divided into five groups as the following; Group 1 (Gp1) was negative control; (Gp2-5) inoculated i.p with 2×10 6 Ehrlich Ascites Carcinoma (EAC) cells/mouse. After one day, Gp3, Gp4 and Gp5 injected with Cis (2 mg/kg), EDTA (25 mg/kg) and Cis (2 mg/kg)/EDTA (25 mg/kg) for six days, respectively. At day 14, all groups were sacrificed to assess the tumor profile, liver enzymes (alanine transaminases and aspartate transaminases), kidney function (urea and creatinine) and electrolytes (Na + , K + and Ca 2+). The results showed that the i.p LD 50 of EDTA was 250 mg/kg. Treatment with EDTA alone did not show any antitumor activity and did not interfere with the antitumor efficacy of Cis. Biochemical findings revealed that EDTA had mild toxicity on liver and kidneys functions. In summary, EDTA had no antitumor effect and did not alter the Cis efficacy.