Synthesis and in vitro antitumor activity of novel acylspermidine derivative N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide (AAHD) against HepG2 cells.

Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.

Size controlled ultrafine CeO2 nanoparticles produced by the microwave assisted route and their antimicrobial activity.

Cerium oxide (CeO2) nanoparticles (NPs) have a wide range of biological and biomedical applications. This work describes a new methodology for producing ultrafine, highly uniform NPs with controlled sizes using the chemical microwave assisted route. The size of CeO2-NPs decreased from 10 to 5 nm by increasing the molar ratio of cerium nitrate Ce(NO3)3.(6H2O) to that of hexamethylenetetramine (C6H12N) from 1:20 to 20:20. Detailed information about their structural characterization was obtained from the XRD, UV-visible, photoluminescence, Raman spectroscopy, SEM, TEM and AFM. These CeO2-NPs were tested as antimicrobial agent against Gram-negative (Escherichia.coli), Gram-positive (Bacillus.subtilis) bacteria and yeast (Saccharomyces cerevisiae). The obtained results showed significant inhibition of these strain even at low concentration of CeO2-NPs. The CeO2-NPs with the molar ratio 5:20 had the most effective inhibition against E.coli (~70%) at a concentration of 20 µL. The CeO2-NPs with the ratio 12:20 were found to be the most effective against B.subtilis (inhibition ~68%). On the other hand, CeO2-NPs synthesized with the 20:20 molar ratio caused the highest inhibition for S. cerevisiae (~60%). It is observed that at higher NPs concentration (i.e., >20 µL) the inhibition of these strains decreased. The antimicrobial activity may be attributed to the penetrating power of CeO2-NPs size beside the generated oxygen species radicals that caused inhibition of bacterial growth.

Role of hesperetin in LDL-receptor expression in hepatoma HepG2 cells.

BACKGROUND: High plasma concentration of low-density lipoprotein cholesterol (LDL-c) plays a significant role in the incidence of atherosclerosis and coronary heart diseases. The aim of this study was to investigate the mechanism by which the citrus flavonoid, hesperetin, regulates the LDL receptor (LDLr) gene in the human liver using the human hepatoma cell line, HepG2. METHODS: Luciferase reporter gene assays were performed (in the absence of lipoprotein) to measure the activity of the LDLr promoter and the promoters of the sterol regulatory element binding protein (SREBP) transcription factors that control the LDLr promoter. RESULTS: Only SREBP-1 promoter activity was significantly increased 4 h after exposure to 200 µM hesperetin. However, after 24 h incubation with 200 µM hesperetin, the activities of all the promoter-constructs, SREBP-1a, -1c, -2 and LDLr, were significantly increased. The effects of 200 µM hesperetin on elevating LDLr mRNA levels were possibly due to regulation of LDLr gene transcription by SREBP-la and SREBP-2. CONCLUSIONS: We conclude that 200 µM hesperetin was likely to have stimulated LDLr gene expression in human hepatoma HepG2 cells via increased phosphorylation of PI3K andERK1/2, which increased SREBP-1a and SREBP-2 mRNA levels and enhanced the maturation of the encoded proteins. This may lead to lower plasma LDL cholesterol; therefore, diets supplemented with hesperidin might provide cardio-protective effects and reduce mortality and morbidity from coronary heart diseases.

Antioxidant status and hormonal profile reflected by experimental feeding of probiotics.

Excessive production of free radicals can result in tissue damage, which mainly involves generation of hydroxyl radical and other oxidants. Such free radical-induced cell damage appears to play a major role in the pathogenesis of many diseases. Probiotics have been used therapeutically to modulate immunity, improve digestive processes, lower cholesterol, treat rheumatoid arthritis, and prevent cancer. The proposed research was designed to evaluate the changes in oxidative and antioxidative profile in addition to metabolic-related hormones of living animal model, which may generally affect the health status. Two groups of rabbits (10 animals each) were allocated in hygienic cages of controlled animal house. Control group received standard diet, and the other group received the same diet containing one probiotic for 30 days. Lactate dehydrogenase (LDH) activity in leukocytes, blood glucose, reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were estimated in different tissues. Malondialdehyde (MDA) and total proteins were also determined in different tissues. Certain hormones related to metabolism and growth were also evaluated. Leukocytic LDH activity was significantly increased along with nonsignificant increase of blood glucose in probiotics-fed animals. Results showed significant decreases in the levels of triiodothyronine and thyroid-stimulating hormone but showed significant elevations in thyroxine, insulin, growth hormone, and testosterone levels in animals fed with probiotics. Total proteins content was highly significantly elevated in liver, kidneys, and muscles of probiotic-administered animals. Microsomal GSH level was significantly decreased only in skeletal muscles of probiotic-treated animals. MDA was significantly lowered in animal tissues fed with probiotics. GSH-Px activity was elevated in hepatic and muscular microsomes of probiotic-supplemented animals while it was nonsignificantly increased in renal microsomes. Microsomal SOD activity was elevated in liver, kidneys, and skeletal muscles of probiotics-administrated animals. It is concluded that supplementation of probiotic may enhance antioxidant efficacy and scavenge free radicals and thus may be used as a preventive measure for protection against free radicals-induced disorders.

Biochemical modulation of cell energy by 2-deoxyglucose and malonate in 7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats.

The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5'-triphosphate) and oxidative stress in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II-V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.

Phytochemical analysis of Convolvulus hystrix Vahl and its biological effects in rats.

"Convolvulus hystrix Vahl" is a plant that has been known to Ancient Egyptians and to Arabs and its root was used traditionally as a purgative. Our attention was directed to the root bark as we observed that the largest part of the plant is deeply impeded underground. The work plan involved testing experimental animals for the influence of aqueous root bark extract on carbohydrate, fat and protein metabolisms as reflected on the growth and relevant laboratory metabolic assessment parameters. Proximate analysis showed high percentages of moisture (85%) and total lipids (7.2%) and surprising amounts of elements such as barium, strontium, rhodium and tellurium (1.7 mg, 3.1 mg, 8 mg and 9.1 mg/g ash, respectively). Random serum glucose value showed a significant decrease in the treated female group (p < 0.05). Serum total proteins of treated female group were found to be increased significantly (p < 0.001), while it was found to be decreased in the relevant treated male group (p < 0.01), together with a significant decrease in blood urea nitrogen (p < 0.05), with a significant increase in the serum creatinine (p < 0.05). Concerning serum fat metabolic parameters, a significant decrease in the serum triglycerides and high-density lipoproteins (p < 0.01 and p < 0.01, respectively) were found. We concluded that the presence of huge amount of polyphenolics such as tannins is responsible for the overall results documented as growth retarding and antinutritional factors. The results were motivating and pointed out to the possible opening of vast areas of research in the field of natural products. We recommend a series of biochemical and pharmacological studies concerning different parts of the plant as well.

Hypermethylation of P15, P16, and E-cadherin genes in ovarian cancer.

Both p16 and p15 proteins are inhibitors of cyclin-dependent kinases that prevent the cell going through the G1/S phase transaction. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent interactions between adjacent epithelial cells. Two groups of patients were selected: the first group suffered from epithelial serous ovarian tumors and the second group suffered from benign ovarian lesions; ovarian tissue samples from all the subjects (benign and malignant) were subjected to methylation-specific polymerase chain reaction for methylated and unmethylated alleles of the genes (E-cadherin, p15, and p16). Results obtained showed that aberrant methylation of p15 and p16 genes were detected in 64.29 and 50% of ovarian cancer patients, while E-cadherin hypermethylation was detected in 78.57% of ovarian cancer patients. Methylation of E-cadherin was significantly correlated with different stage of disease (p < 0.05). It was found that the risk of E-cadherin hypermethylation was 1.347-fold, while risk of p15 hypermethylation was 1.543-fold and p16 was 1.2-fold among patients with ovarian cancer than that among patients with benign ovarian lesions. In conclusion, Dysfunction of the cell cycle and/or the cell-cell adhesion molecule plays a role in the pathogenesis of ovarian cancer and that the analysis of the methylation of p15 and E-cadherin genes can provide clinically important evidence on which to base the treatment.

Management of Hyperglycaemia by Ethyl Acetate Extract of Balanites aegyptiaca (Desert Date).

Reactive oxygen species play a significant role in the pathogenesis of retinopathy in diabetes patients. The current study aimed to assess the effect of ethyl acetate extract (EAE) from Balanites aegyptiaca (10, 25 or 50 mg/kg b.w.) in experimental diabetic rats. To achieve this aim, five groups of male rats were included: control, diabetic, and diabetic rats treated with 10, 25, and 50 µg/kg b.w. of EAE for eight weeks. Our results suggests a protective role of EAE against oxidative stress induced by streptozocine. EAE treatment produced a reduction in blood glucose levels, HbA1c, malondialdehyde and vascular endothelial growth factor (VEGF) in diabetic retina (p < 0.001), as well as an enhancement in antioxidant capacity against streptozocine-induced oxidative stress. Tumor necrosis factor alpha (TNF-α), interleukin (IL-1ß) and vascular endothelial growth factor (VEGF) were significantly reduced in diabetic rats treated with EAE, compared with untreated diabetic rats. Analysis of EAE by GC-MS indicated the presence of ß-sistosterol. Overall, EAE modulates oxidative stress induced by streptozocine and enhances antioxidant activity, which may provide additional endothelial protection in retina of diabetic rats. These results hold great promise in the management of diabetic complications.

Impact of probiotic-supplemented diet on the expression level of lactate dehydrogenase in the leukocytes of rabbits.

Probiotics are known as living, nonpathogenic microorganisms that colonize the intestine and provide benefit to the host. The present study aims to measure one important energy metabolism-related enzyme activity in blood of rabbits fed on probiotics of recommended concentration. In addition, it also aims for the evaluation of the expression level of lactate dehydrogenase (LDH) enzyme using reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Two groups of rabbits are used: control group receiving normal standardized diet and the other probiotic-supplemented group receiving the same diet containing probiotic, namely, Mega acidophilus (200 million cfu/kg body weight/day) for 4 weeks. The obtained results revealed that the rabbits supplemented with probiotics showed a significant decrease in the levels of serum total cholesterol (TC), triacylglycerol, high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) when compared with control group. Risk factors detected by measuring TC/HDL-c and LDL-c/HDL-c ratios showed statistically significant decrease in probiotic-supplemented rabbits when compared with control group. In addition, blood glucose and total LDH activity were elevated in probiotic-supplemented rabbits when compared with control group. RT-PCR products of LDH-M gene produced two specific amplicons. One amplicon has the expected size of 243 bp from all samples of rabbits as revealed by GelPro software. The level of LDH-M expression was found to be increased in the probiotic-supplemented group. However, unexpected amplicons are produced at 586 bp in all the samples, which may be a dimeric form of the amplified region. It was concluded that this probiotic blend is beneficiary for the metabolic reactions of lipids in the body. Moreover, LDH expression level can be considered as a biomarker for the effect of probiotic and hence monitoring the metabolic changes as reflected from its administration.

Molecular docking targeting autophagy pathway mediate abrogation of NASH by specific functional foods: update review.

Autophagy is a very well-conserved self-digestive mechanism that transports unwanted or disposable cytoplasmic debris to lysosomes for destruction, including misfolded proteins and damaged organelles. Advanced liver illnesses can develop from the prevalent clinical condition known as non-alcoholic steatohepatitis (NASH). There is no effective treatment, is still unclear. Therefore, in order to create novel therapeutics, it is necessary to comprehend the pathogenic pathways causing disease onset and progression. Natural components from medicinal plants are currently the subject of a larger number of studies since they provide fresh promise for NASH. This review provided an overview of the aetiology of NASH, in addition the role of natural products as alternative or complementary therapeutic agent for management of NASH via autophagy induction. It was concluded that, alternative and complementary supplement of natural functional food as Arabica coffee that rich with chlorogenic acid targeting autophagy mechanism mediate amelioration effect of NASH.

Molecular docking analysis of some medicinal extracts for pro-apoptotic, antiinflammatory and antioxidative activities using HCC cell lines.

We investigated the biological activities of 14 medicinal plants from Saudi Arabia as anti-inflammatory, antioxidant and anti-proliferative properties using hepatocellular carcinoma (HCC) cell lines. Hexane extracts exhibited the maximum inhibitory activities against albumin denaturation compared with those of other solvents. Baccharoides schimperi hexane extract showed the highest anti-inflammatory while Ocimum basilicum methanol extract showed significantly high hydroxyl radical scavenging activity (p < 0.001). B. schimperi methanol extract showed highest cytotoxicity and anti-proliferation activity (IC50; 25 µg/ml) in hepatocellular carcinoma cell line. Annexin V and caspase-9 activities were induced significantly (p < 0.001) by B. schimperi and the response increased in a dose dependent compared with untreated cells (p < 0.001). The docking scores showed a low docking energy binding of 2-Cyclohexylpiperidine of B. schimperi with COX-2, (-16.62 kcal/mol), high affinity for apoptotic and anti-inflammatory potency It can be concluded that, B. schimperi active ingredients as 2-Cyclohexylpiperidine and phytol contributed to its biological activity.

Protective effect of vitamin E and epicatechin against nicotine-induced oxidative stress in rats.

Nicotine is a major pharmacologically active and addictive component of tobacco smoke, which is regarded to be a primary risk factor in the development of cardiovascular and pulmonary diseases. Epicatechin is one of the most potent antioxidants present in the human diet. Particularly high levels of this compound are found in tea, apples and chocolate. It has been reported that tea extracts and/or its constituents have antibacterial, antiviral, antioxidative, antitumor and antimutagenic activities. Vitamin E is a major lipid-soluble antioxidant vitamin and free radical scavenger, presents as an integral component of cellular membranes and has important biological functions. The primary mechanism by which vitamin E is proposed to prevent cancer is through their antioxidant properties. The goal of this study is to evaluate the effect of epicatechin alone or combined with vitamin E in inhibiting the oxidative stress induced by nicotine in rats. Results obtained indicated that there was a significant elevation in the levels of malondialdhyde (MDA) in nicotine injected rats. The combined treatment (epicatechin + Vit E) group showed a potential reduction of these parameters more than individual treatment. The activities of superoxide dismutase, catalase and glutathione peroxidase were found significantly higher in combined treated than untreated rats. In nicotine group, a negative significant correlation between reduced glutathione and MDA (r = -0.92) was observed. In conclusion, these results suggested that the supplementation of diet with epicatechin and vitamin E provided antioxidant defense with strong chemopreventive activity against nicotine-induced carcinogenesis.

Detection of polycyclic aromatic hydrocarbons in different types of processed foods.

Polycyclic aromatic hydrocarbons (PCAHs), particularly those with a high molecular weight, have been classified as probable carcinogens to humans. The aim of the present study is to determine the levels of PCAHs in samples of meat, fish, chicken, fried potato, and toasted bread, which will be thermally processed using conventional and microwave ovens. Different samples will be collected and analyzed for five PCAHs including pyrene, benzo(a)anthracene, benzo(e)pyrene, benzoflouroanthene, and benzo(a)pyrene. The analytical method involves saponification with methanolic potassium hydroxide, extraction with cyclohexane, and determination by high-performance liquid chromatography. The obtained results showed that there is a variation in the detected PCAHs in different foodstuffs. Fried potato processed by conventional oven or microwave oven showed none of the selected studied PCAHs. It was found that, chicken showed higher content levels of total PCAHs than the meat and fish. Data are the highest mean concentrations of fluoranthene and benzo(a)pyrene but within low limit. The obtained results were compared with international permissible levels to avoid pollution, which may cause hazardous effects on individual and society.

Impact of aqueous doash extract on urinary mutagenicity in rats exposed to heterocyclic amines.

Doash (Origanum majorana) is an herbaceous plant found commonly in Saudi Arabia. It is used as a food flavor and a folk remedy to treat a number of diseases. The 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are the most abundant of the heterocyclic amine carcinogens present in cooked food. In the present study, the potential of doash tea to influence carcinogen metabolism was investigated indirectly using heterocyclic amines as model mutagens, IQ and PhIP. Results obtained showed that doash tea had no influence on body weight in both the studies. Rats were treated with different doses of IQ (1, 3, 5 and 10 mg/kg) or PhIP (1, 5, 10 and 20 mg/kg). The selected dosage was 5 mg/kg for both heterocyclic amines. Results obtained revealed that rats treated with doash tea and given a single dose of the heterocyclic amines, whether for 1 day (short-term) or for 1 month (long term), showed a statistically significant decrease in their excretion of indirect mutagens (IQ or PhIP). Following treatment of the rats with a single oral dose of IQ or PhIP, the highest mutagenic activity determined in the presence of an activation system was excreted in the urine after 24 h, with much lower levels of mutagencity being excreted during subsequent elimination from the body. No mutagenicity was observed in the absence of an activation system that is direct-acting mutagenicity using (IQ and PhIP). Statistical analysis revealed that, in comparison with the control group, the aqueous doash extract significantly reduced the mutagenic response after 24 h. It was concluded that doash extract significantly decreased the excretion of mutagens in comparison with the control group (water only).

Oxygen scavenging, anti-inflammatory, and antiglycation activity of pomegranate flavonoids (Punica granum) against streptozotocin toxicity induced diabetic nephropathy in rats.

Bioactive natural products are essential components for drug development. Protein glycation in diabetic subjects leads to diabetic complications as nephropathy and neuropathy. We investigated the impact of pomegranate hexane extract (PHE) as antioxidant, anti-inflammatory, and antiglycation in diabetic rats. Gas chromatography/mass spectrum (GC/MS) analysis of PHE revealed presence of resorcinol, catechol, tau-cadinol, metacetamol, scopoletin, phytol, and phenol, 3-pentadecyl as the most active ingredients that related to biological activity. Results obtained showed that, PHE increased serum aldose reductase and total antioxidant activity compared with untreated diabetic rats (p < 0.001). In addition, PHE exert antioxidant by enhancing, catalase and SOD (p < 0.001) and decreased MDA (p < 0.001), anti-inflammatory by inhibition production of 1 ß (IL-1ß), tumor necrosis factor (TNF-α) (p < 0.001), and AGEs (p < 0.001) against nephropathy in diabetic rats compared with untreated group. It was concluded that, pomegranate is promising in development a functional biomolecule in treatment and protection against diabetic complications as nephropathy. More study required to investigate the molecular action of these molecules.

Inhibition of dipeptidyl peptidase-4 (DPP4), antioxidant, antiglycation and anti-inflammatory effect of Ferulic acid against streptozotocin toxicity mediate nephropathy in diabetic rats.

The protein glycation due to high blood glucose mediate release of inflammatory intermediate contributes in the development of diabetic nephropathy. Ferulic acid (FA) is a phenolic compound distributed in different foods as whole grains. Inhibitors of DPP4 improve GLP-1-mediated insulin secretion and inhibit liver gluconeogenesis. This study investigated the impact of FA as anti-inflammatory, antioxidant and antiglycation against streptozotocin-induced diabetic nephropathy in rats. This study was carried out on total ninety male rats allocated into six (each 15 rats); group I (control). All other animals (groups II-VI) were receiving 65 mg/kg STZ for induction of diabetes. Rats in group II (untreated diabetic). Rats in groups III-V were treated with FA (10, 20, 30 mg/kg bw) respectively, i.p. for 8 weeks. Group VI received 10 units insulin daily, sc. Fasting blood samples were subjected for assay of glycated hemoglobin (HA1c), serum MDA, aldose reductase, total antioxidant, DPP4 while kidney tissue subjected for assay of malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), IL-1ß and AGEs. Data obtained showed that, FA showed antioxidant activity by reducing MDA and enhancement antioxidant activity compared with untreated rats (p < 0.001) with dose dependence. In addition, FA reduced the activities of aldose reductase, DPP4 (p < 0.001), decreased IL-6, TNF-α and AGEs versus untreated rats (p < 0.001). Histological investigation revealed an improvement in the nephron structure in diabetic rat treated with FA versus untreated group. It was concluded that, FA possesses a potent antioxidant and anti-inflammatory and DPP4 inhibitor. For that, it was considered as a protective agent against the risk of diabetic nephropathy and can be used as alternative or complementary supplement.

Detection the severity of organophosphate intoxication using sensitive serum biomarkers S100B and amyloid ß (Aß) in Egyptian subjects.

Organophosphate (OP) is a compound considered the main leading cause of morbidity and mortality from poisoning worldwide. Serum pseudocholinesterase was evaluated as a diagnostic indicator; it cannot be used to monitor therapy or severity of the intoxication. The rationale of the current study was to evaluate sensitivity, specificity, and cut-off values of serum S100B and amyloid ß for neurological affection severity. This study was carried out on sixty OP-impaired patients; in addition, 20 normal controls were included. Serum liver and kidney function tests, malondialdehyde, pseudocholinesterase, and the levels of S100B and amyloid ß (Aß) were determined. Data showed that Pearson's analysis indicated that the serum level of S100B was positively correlated with Aß. On the contrary, the activity of pseudocholinesterase was negatively correlated with both of S100B and Aß. Serum ALT, AST, creatinine, urea, acetylcholine, and MDA levels were elevated while pseudocholinesterase activity was reduced in moderate and severe OP intoxication versus control. A drastic elevation (p<0.001) in the levels of S100B and Aß was performed in the patient group suffering from OP intoxication versus the normal group. The diagnostic statistical validation of targeted parameters in distinguishing between moderate OP intoxication and control clarifies that S100B displayed the best AUC (0.997) followed by Aß (AUC=0.992), while the diagnostic veracity of S100B and Aß in setting apart severe OP-intoxicated and normal subjects stated the symmetric efficacy of potential markers. It was concluded that the significant changes in the levels of S100B and Aß were directly proportional to the degree of severity of OP intoxication.

Rhus tripartite methanolic extract alleviates propylparaben-induced reproductive toxicity via anti-inflammatory, antioxidant, 5-α reductase in male rats.

Evidence showed that herbal medicine could be beneficial for protection against diseases that may be exist in consequence of exposure to environmental toxicants. Propylparaben (PrP) is used as preservative in food, pharmaceuticals, and cosmetics. It is classified as one of endocrine disruptive chemicals (EDCs). This study evaluated the protective effect of Rhus tripartita methanolic extract (RTME) against reproductive toxicity induced by PrP in male rats. A total of 60 Wister albino rats were divided into four groups (15 rats for each group). Group I (control): rats received the vehicle (DMSO), group II: normal rats received RTME (10 mg/kg/day), group III: rats received PrP (10 mg/kg/day), and group IV: rats received PrP (10 mg/kg/day) and RTME (10 mg/kg/day) for 4 weeks. At the end of experiment, levels of testosterone, dihydrotestosterone (DHT), and 5α-reductase were analyzed in sera. Data obtained showed a significant reduction in the levels of testosterone, dihydrotestosterone (DHT), and 5α- reductase in rats given PrP versus control (p < 0.001) and RTME treatment improved these parameters but not returned to normal. Data obtained showed a significant elevation in levels of IL-6 and TNF-α in the testis of rats given PrP versus control (p < 0.001), these inflammatory mediators were significant reduced in rats treated with RTME compared with untreated rats (p < 0.001). There was a positive correlation between level of DHT and antioxidant enzymes activities (r = 0.56). A significant elevation in the levels of MDA with reduction in the activities of GST, GSPx, SOD, and catalase (p < 0.001) in rat testicular tissues of PrP group versus control (p < 0.001) was found. Treatment with RTME significantly reduced the levels of MDA and enhanced activities of GST, GSPx, SOD, and catalase (p < 0.001) compared to untreated group (p < 0.001). In conclusion, the active ingredient components of RTME abrogate the toxicity of PrP by exhibiting antioxidative and anti-inflammatory effects, enhancing 5-α reductase with improved hormonal status against PrP- induced testicular damage. Toxicity of propylparaben, and effect of Rhus tripartita methanolic extract.

Evaluation of the in vitro antimutagenic effect of Doash tea aqueous extracts.

Human carcinogens are formed mainly due to the lifestyle and diet that is followed. It is well known that dietary factors play a crucial role in the aetiology of human cancer. The new attractions of drug discovery using natural products remain an important issue in the current herbal medicine research. The present study aimed to evaluate the antimutagenic activity of the water extracts of Doash leaves against several known mutagens, both direct- and indirect-acting, belonging to different chemical classes. These classes are heterocyclic amines (HAs), polycyclic aromatic hydrocarbons and nitrosamines. The antimutagenic activity will be determined in Salmonella/microsomal system (Ames) using strains of Salmonella Typhimurium. Four Salmonella bacterial strains (TA98, TA97, TA100 and TA1530) were used in the present study. Results obtained showed that Doash extract possesses powerful antimutagenic properties, which impair the deleterious effects of various chemicals used in this study. One possible mechanism involved in this protection is the inhibition of the metabolic activation of chemical carcinogens to their reactive metabolites. We also suggest that the health benefits of Doash could be derived from the additive and synergistic combinations of the various phytochemicals present in Doash leaves. Other studies should also be conducted to determine the active components of Doash leaves, including macronutrients, micronutrients and other phytochemicals. Clinical studies should be performed before any claims that Doash consumption offers chemoprotection against cancer can be made.

Assessment of the antimutagenic effect of Doash tea extract fractions.

Origanum majorana L (Doash) is one of the traditional remedy that is used as a tea and to treat ailments, in the Kingdom of Saudi Arabia. The present study has attempted to evaluate the inhibitory action of Doash fractions on the bioactivation of selected food mutagens and direct-acting mutagens. Four Sallmonella bacterial strains (TA98, TA97, TA100 and TA1530) were used in the present study. These strains contain different mutations in the histidine operon, allowing the bacteria to detect different types of mutation. The two strains (TA98 and TA97) are capable of detecting frameshift mutations, while TA100 and TA1530 are able to detect base-pair substitutions. The liver homogenate and other subcellular fractions were prepared. Identification of Doash fractions was conducted using the high-performance liquid chromatography/mass spectrometry system. The results of the present study demonstrated that the Doash tea fraction components have the ability to reduce the in vitro mutagencity of several promutagens, which were employed in this study. Fraction No. 5 (with the highest content of solid) was the most potent inhibitor of the mutagenicity of all promutagens employed in this study. The antimutagenic effect of Doash tea extract, and its various fractions, was pronounced, indicating that the metabolism of cytochrome P450 1A2 isozyme is likely to be inhibited.