Ali H. El-Far

Thymoquinone Anticancer Discovery: Possible Mechanisms.

Medicinal plants are known for their many advantages, including the ability to treat diseases such as cancer. Nigella sativa and its active constituent thymoquinone (TQ) have long been used in traditional medicine for treating various conditions related to the respiratory and gastrointestinal systems as well as breast, colorectal, gastric, hepatic, pancreatic cancers and leukemia. TQ has been documented to possess chemo-preventive and chemotherapeutic antitumor effects. Studies reported that TQ inhibits the growth of cancer cells in animal models and culture tumors. This review summarizes the in vitro and in vivo possible mechanisms of TQ anticancer effect.

Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression

Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.

Hepatoprotective efficacy of Spirulina platensis against lead-induced oxidative stress and genotoxicity in catfish; Clarias gariepinus

Lead (Pb) is a toxic environmental pollutant that induces a broad range of biochemical and physiological hazards in living organisms. We investigated the possible hepatoprotective effects of Spirulina platensis (SP) in counteracting the Pb-induced oxidative damage. Ninety-six adult African catfish were allocated into four equal groups. The 1st group (control) fed basal diet while the 2nd group (Pb-treated) fed on basal diet and exposed to 1mg Pb(NO3)2/L. The 3rd and 4th groups fed SP-supplemented basal diets at levels of 0.25% and 0.5%, respectively and exposed to Pb. Serum samples were used to analyze hepatic function biomarkers, electrolytes, and oxidant and antioxidant status. Lipid peroxidation and DNA fragmentation were determined in the liver tissues. Pb exposure induced hepatic dysfunction, electrolytes (Na+, K+, Ca+2, and Cl-) imbalance, as well a significant decrease in GSH content, and LDH, AChE, SOD, CAT and GST enzymes activity. SP supplementation reverted these biochemical and genetic alterations close to control levels. This amelioration was higher with 0.5% SP and at the 4th week of exposure, showing concentration- and time-dependency. Thus, the current study suggests that SP could protect the catfish liver against lead-induced injury by scavenging ROS, sustaining the antioxidant status and diminishing DNA oxidative damage. The dietary inclusion of SP can be used as a promising protective agent to counteract oxidative stress-mediated diseases and toxicities.

Hepatoprotective efficacy of Nigella sativa seeds dietary supplementation against lead acetate-induced oxidative damage in rabbit – Purification and characterization of glutathione peroxidase

Lead (Pb) is a toxic ubiquitous environmental pollutant that induces hepatotoxicity in both animals and humans. The ability of Nigella saliva seeds (NSS) in ameliorating lead acetate (PbAc)-induced hepatic oxidative damage was investigated using a rabbit model. Forty New Zealand rabbits were given feed and water ad libitum. They were allocated randomly into four groups: control; PbAc (5g/L drinking water); NSS (20g/kg diet) and NSS+PbAc groups. After two months, liver samples were collected and analyzed for malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPx) contents. Purification and characterization of GPx were also evaluated. PbAc exposure significantly (p<0.05) increased MDA (lipid peroxidation biomarker) and reduced the GSH levels and the GST and GPx activities. Concurrently supplemented NSS significantly (p<0.05) decreased MDA levels and restored the GSH, GST, and GPx contents successfully. Electrophoretically, the homogeneous GPx preparation from the liver had a specific activity of 30.44 U/mg protein and a yield of 1.31%. The Km values for cumene hydroperoxide were 4.76μM in control, PbAc and NSS+PbAc groups, and 4.09μM in NSS group. The GPx reaction had a temperature optimum 40°C, pH optimum 8 and molecular weight 21 kDa. The obtained data indicated the potent efficacy of NSS against PbAc-induced oxidative stress; that was mediated through induction and activation of antioxidants, particularly GPx and scavenging free radicals. Moreover, the purified hepatic GPx is characterized as a selenoprotein (Se-GPx).

Possible Anticancer Mechanisms of Some Costus speciosus Active Ingredients Concerning Drug Discovery.

Costus speciosus is native to South East Asia, especially found in India, Srilanka, Indonesia and Malaysia. C. speciosus have numerous therapeutic potentials against a wide variety of complains. The therapeutic properties of C. speciosus are attributed to the presence of various ingredients such as alkaloids, flavonoids, glycosides, phenols, saponins, sterols and sesquiterpenes. This review presented the past, present, and the future status of C. speciosus active ingredients to propose a future use as a potential anticancer agent. All possible up-regulation of cellular apoptotic molecules as p53, p21, p27, caspases, reactive oxygen species (ROS) generation and others attribute to the anticancer activity of C. speciosus along the down-regulation of anti-apoptotic agents such as Akt, Bcl2, NFκB, STAT3, JAK, MMPs, actin, surviving and vimentin. Eventually, we recommend further investigation of different C. speciosus extracts, using some active ingredients and evaluate the anticancer effect of these chemicals against different cancers.

Exogenous dietary lysozyme improves the growth performance and gut microbiota in broiler chickens targeting the antioxidant and non-specific immunity mRNA expression

Supplementation of exogenous enzymes in chickens has been widely practiced, yet mechanisms responsible are not fully delineated. To investigate the effects of the dietary lysozyme on the growth performance and immunity of broiler chickens, a total of 120 one-day-old Ross 308 chicks were randomly allocated into four groups, each having three replicates (30 birds/group). The chicks were fed the starter (1–21 d) and grower (22–35 d) diets supplemented with 0 (control), 70 (LYZ70), 90 (LYZ90) and 120 (LYZ120) g of lysozyme 10%® per ton of basal diet for five weeks. The results revealed significant improvement in the growth performance and gut environment. There were significant decreases (P < 0.05 or 0.01) in the harmful fecal Coliform and Clostridia and an increase (P ˂ 0.05) in the beneficial Lactobacillus in the lysozyme-supplemented groups, especially in LYZ90. Moreover, the mRNA expressions of Cu, Zn-superoxide dismutase (SOD1), glutathione peroxidase (GSH-Px), interferon-gamma (IFN-γ), interleukin-10 (IL-10), and interleukin-18 (IL-18) were upregulated in response to lysozyme supplementation. In comparison to control, LYZ90 fed birds had a significant increase (P < 0.01) in the GSH-Px gene expression that enhances the antioxidant status of the gut. Expression of the biomarkers involved in the gut non-specific immunity indicated significant increases in the mRNA expression of INF-γ (P < 0.001), IL-10 (P < 0.001), and IL-18 (P < 0.05) in LYZ90 group. Also, serum globulin levels were significantly elevated (P ˂ 0.05) in lysozyme-supplemented groups. Histologically, the intestinal villi length and crypts depth were also enhanced (P ˂ 0.05) by dietary lysozyme supplementation. In conclusion, supplementation of broiler chickens with exogenous lysozyme, especially at 90 g of lysozyme per ton of basal diet dose rate, improved the growth performance, gut antioxidant status, and nonspecific immunity of broiler chickens.

The Role of Receptors for Advanced Glycation End Product in PancreaticCarcinogenesis

Pancreatic cancer is the fourth-leading cause of cancer deaths worldwide that considered as the malignant tumor with the poorest prognosis and the lowest survival rate. This extremely violent disease is rarely diagnosed at an early level and difficult to treat due to its resistance to radiation therapy and chemotherapy. Here, we show that the receptor for advanced glycation end products (RAGE) and its ligands, advanced glycation end products (AGEs), high-mobility group box 1 (HMGB1) and S100 protein family are required for pancreatic cancer development, angiogenesis and metastasis through up-regulation of some anti-apoptotic molecules as matrix metalloproteinase -9 (MMP-9), kinase insert domain receptor (KDR), vascular endothelial growth factor (VEGF), platelet-derived growth factor-B (PDGF-B), hypoxia-inducible factor 1 (HIF1α), signal transducer and activator of transcription 3 (pSTAT3) and nuclear factor kappa B (NF-κB). In addition to the decrease in reactive oxygen species (ROS) those favouring the cancer cell growth and metastasis. The role of RAGE in pancreatic carcinogenesis needs further studies to investigate the relationship of RAGE with other anti-apoptotic and apoptotic molecules and examine the therapeutic potentials of anti-RAGE drugs for pancreatic cancer.

Impact of diesel exhaust exposure on the liver of mice fed on omega-3 polyunsaturated fatty acids-deficient diet

Exposure to diesel exhaust (DE) exacerbates non-alcoholic fatty liver disease, and may systemically affect lipid metabolism. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have anti-inflammatory activity and suppresses hepatic triacylglycerol accumulation, but many daily diets are deficient in this nutrient. Therefore, the effect of DE exposure in mice fed n-3 PUFA-deficient diet was investigated. Mice were fed control chow or n-3 PUFA-deficient diet for 4 weeks, then exposed to clean air or DE by inhalation for further 4 weeks. Liver histology, plasma parameters, and expression of fatty acid synthesis-related genes were evaluated. N-3 PUFA-deficient diet increased hepatic lipid droplets accumulation and expression of genes promoting fatty acid synthesis: Acaca, Acacb, and Scd1. DE further increased the plasma leptin and the expression of fatty acid synthesis-related genes: Acacb, Fasn, and Scd1. N-3 PUFA-deficient diet and DE exposure potentially enhanced hepatic fatty acid synthesis and subsequently accumulation of lipid droplets. The combination of low-dose DE exposure and intake of n-3 PUFA-deficient diet may be an additional risk factor for the incidence of non-alcoholic fatty liver disease. The present study suggests an important mechanism for preventing toxicity of DE on the liver through the incorporation of n-3 PUFAs in the diet.

Dietary Supplementation of Phoenix dactylifera Seeds Enhances Performance, Immune Response, and Antioxidant Status in Broilers

The date palm (Phoenix dactylifera) seeds were utilized in some traditional medical remedies and have been investigated for their possible health benefits. This proposed study wanted to assess the effect of date palm seeds (DPS) dietary supplementation in comparison to mannan-oligosaccharides (Bio-Mos®) and β-glucan over antioxidant and immunity events that have effect on growth and carcass performances of broilers. An aggregate of 180, one-day-old, chicks were raised in the wire-floored cages and allotted into control, Bio-Mos (0.1%  Bio-Mos), β-glucan (0.1%  β-glucan), DPS2 (2% date crushed seeds), DPS4 (4% date crushed seeds), and DPS6 (6% date crushed seeds) groups. Broilers in DPS2 and DPS4 groups showed significant variations (P < 0.05) in relative growth rate (RGR), feed conversion ratio (FCR), and efficiency of energy utilization in comparison to control group. Moreover, all DPS fed groups showed significant increases (P < 0.05) in serum reduced glutathione (GSH) values. Meanwhile, both serum interferon-gamma (IFN-γ) and interleukin-2 (IL-2) levels were significantly increased (P < 0.05) in DPS2. Consequently, obtained data revealed a substantial enhancement of performance, immunity, and antioxidant status by DPS supplementation in broiler that might be related to the antioxidant and immune-stimulant constituents of P. dactylifera seeds.

Exogenous dietary enzyme formulations improve growth performance of broiler chickens fed a low-energy diet targeting the intestinal nutrient transporter genes

Diminishing the cost of broiler chicken diet is a critical issue in the poultry industry. Numerous studies were performed to achieve this pivotal objective by diet supplementation with alternative feed additives. In the current study, low-energy broiler rations were supplemented with different commercial multienzyme formulations to minimize the cost, and increase the digestibility and absorption of the digested macronutrients. Cobb Avian 48 broiler chicks (mixed sex, 1-d-old, n = 3120) were randomly allocated into six groups, and each group was subdivided into four replicates (130 birds per replicate). The birds were randomly allocated into a control group fed basal diet (CB); control group fed low-energy diet (CL); and birds fed low-energy diets supplemented with different enzyme formulations. The enzyme formulations used were Xylam 500® (CLX group), Hemicell® (CLH group), Avizyme® (CLA group), and Megazyme® (CLM group,) following the doses recommended by the manufacturers. The growth performance of CLA and CLH group birds was significantly improved when compared with CL. In comparison with CB, Avizyme® significantly (p < 0.001) increased the intestinal PEPT1, GLUT2, ACC, and IL-2 expression; PEPT1 facilitates the absorption of micronutrients. In conclusion, exogenous multienzyme complexes may be included in the low-energy diet to enhance the performance of broiler chickens (Avizyme® ˃ Hemicell® ˃ Megazyme®), and reduce the diet cost by up-regulating the expression of intestinal nutrient transporter genes, and improving the immunity and serum biochemical parameters of broiler chickens.