Protective Effects of Taif Rosewater Against Testicular Impairment Induced By Lead Intoxication In Rats.

This study explored treatment with Taif rosewater (RW) to protect against lead acetate-(PbAc) induced male testicular impairment. Male Wistar rats were divided into four groups and provided drinking water containing 4% Taif RW, PbAc, 4% Taif RW followed by PbAc or normal water (controls). Serum for hormonal assays and testicular tissue for histopathological and immunohistochemical examinations and molecular study were obtained. Epididymal spermatozoa were collected for analysis. PbAc significantly reduced serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone, as well as sperm count and motility percentage. It also caused a significant reduction in SOD and catalase activities, testicular CYTP450SCC , CYP17α, StAR mRNA expressions and the percentage of Bcl-2 immunoreactivity. The percentage of caspase-3 and NF-ĸB immunoreactivities, as well as sperm abnormalities, was increased, as did the testicular degeneration associated with vacuolation and necrosis of spermatogenic cells. Pretreatment with Taif RW significantly reduced the negative effects of PbAc as shown by the increases in serum gonadotropins level, SOD and catalase activities, and percentage of Bcl-2 immunoreactivity, decreases in the percentage of caspase-3 and NF-ĸB immunoreactivities, and improved testicular histology and sperm parameters. These data provide evidence that Taif RW protects against testicular toxicity caused by PbAc.

Moringa oleifera ethanolic extract ameliorates the testicular dysfunction resulted from HFD-induced obesity rat model.

In this study, we estimated the protective role of Moringa oleifera leaf ethanolic extract (MOLE) against obesity-associated testicular dysfunction. Fifty male albino rats were randomly assigned to five groups (n = 10): Group I (basal diet), group II (basal diet plus MOLE orally), group III (high-fat diet-HFD), group IV (HFD plus oral MOLE) and group V (HFD for 8 weeks followed by a basal diet plus oral MOLE for 6 weeks). The study duration extended for 14 weeks. Serum collected to investigate testosterone, FSH and LH levels. Testicular tissues were used to determine levels of SOD, glutathione, catalase and malondialdehyde. Semen was collected to estimate its quality (morphology, motility and concentration). Morphological changes in the testis were investigated by histopathological and immunohistochemical techniques. Compared with both control treatment and MOLE treatment, serum testosterone, FSH, LH, testicular enzymatic catalase, SOD, GSH, survivin immunoreactivity, sperm quality and testicular weight were all significantly decreased in rats treated with HFD, while there were significant increases in testicular malondialdehyde and caspase-3 immunoreactivity. MOLE improved all harmful effects of HFD. Improvements were more pronounced in the protected (G 4) than the treated (G 5) group. MOLE could be a potential solution for obesity-associated fertility problem.

Transcriptome Analysis of Testis from HFD-Induced Obese Rats (Rattus norvigicus) Indicated Predisposition for Male Infertility.

Obesity is a worldwide life-threatening metabolic disorder, associated with various chronic diseases, including male infertility. Obesity was induced by high fat diet (HFD), and testis RNA was used for the transcriptome analysis using RNAseq via Illumina NovaSeq 6000 System and NovaSeq 6000 Kit. Gene expression level was estimated as FPKM (Fragments Per Kilobase of transcript per Million mapped reads). Differential expressed genes (DEGs) were annotated against gene ontology (GO) and KEGG databases. More than 63.66 million reads per sample were performed with 100 bp cutoff and 6 Gb sequencing depth. Results of this study revealed that 267 GO terms (245 biological processes (BP), 14 cellular components (CC), eight molecular functions (MF)), and 89 KEGG pathways were significantly enriched. Moreover, total numbers of 136 genes were differentially expressed (107 upregulated, 29 downregulated) with |FC| ≥ 2 and bh adjusted <0.05. Interesting DEGs were detected, including obesity and lipid metabolism-related genes, immune response-related genes, cytochrome P450 genes, including aromatase were upregulated, whereas genes related to male fertility and fertilization, cell adhesion, and olfactory receptors were downregulated. The combined expression pattern of the DEGs in obese animals indicated an increase in cholesterol metabolism. Furthermore, high aromatase activity enhances the testosterone turnover into estradiol and lowers the testosterone/estradiol (T/E) ratio, which ultimately reduces fertility. In addition, downregulation of cadherens junction components genes leads to the pre-mature release of sperm from Sertoli cells resulting in the reduction of fertility. Moreover, the downregulation of olfactory receptor genes reduces the chemotaxis capacity of sperms in tracking the oocyte for fertilization, which reduces male fertility. Furthermore, various obesity molecular markers were detected in our transcriptome. The results of this study will enhance our understanding of the molecular network of obesity development, development of obesity novel molecular diagnosis markers, molecular bases of obesity-induced infertility, and the development of anti-obesity drugs.

Protective potential of royal jelly against cadmium-induced infertility in male rats.

This study aimed to investigate the protective potential of Royal jelly (RJ) against cadmium (Cd)-induced testicular dysfunction in rats. Thirty-five adult male Wistar rats were assigned into five groups. G I; (control) injected intraperitoneally with saline, G II injected intraperitoneally with a single dose of CdCl2 (1 mg/kg BW), G III received RJ (100 mg/kg BW/day) orally, G IV was pre-treated with RJ for 1 week then, treated with CdCl2 , and G V was co-treated with RJ and CdCl2 . After day 56, serum and tissue samples were collected and analysed. The results showed decreased serum testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), superoxide dismutase, glutathione reductase, sperm motility and count while increased malondialdehyde, nitric oxide, tumour necrosis factor-α (TNF-α) and sperm abnormalities, along with a severely damaged seminiferous tubules epithelium with cytoplasmic and nuclear disruptions following Cd toxicity. Additionally, Cd stimulated testicular mRNA expression of TNF-α while inhibited those of steroidogenic acute regulatory protein, cytochrome P450 cholesterol side chain cleavage enzyme androgen binding protein, FSH-receptor, LH-receptor, androgen receptor, 3ß-hydroxysteroid dehydrogenase (HSD), 17ß-HSD, and cytochrome P450 17A1. These negative alterations of cadmium were greatly reduced by RJ treatment. This study concluded that RJ protects against Cd-induced testicular toxicity.

Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes.

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure.

Clofibric acid induces hepatic CYP 2B1/2 via constitutive androstane receptor not via peroxisome proliferator activated receptor alpha in rat.

Peroxisome proliferator activated receptor α (PPARα) ligands, fibrates used to control hyperlipidemia. We demonstrated CYP2B induction by clofibric acid (CFA) however, the mechanism was not clear. In this study, HepG2 cells transfected with expression plasmid of mouse constitutive androstane receptor (CAR) or PPARα were treated with CFA, phenobarbital (PB) or TCPOBOP. Luciferase assays showed that CFA increased CYP2B1 transcription to the same level as PB, or TCPOBOP in HepG2 transfected with mouse CAR But failed to induce it in PPARα transfected cells. CYP2B expressions were increased with PB or CFA in Wistar female rats (having normal levels of CAR) but not in Wistar Kyoto female rats (having low levels of CAR). The induction of CYP2B by PB or CFA was comparable to nuclear CAR levels. CAR nuclear translocation was induced by CFA in both rat strains. This indicates that fibrates can activate CAR and that fibrates-insulin sensitization effect may occur through CAR, while hypolipidemic effect may operate through PPARα.

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin.

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic alpha,beta-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI-VII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of alpha,beta-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC50 of 5.0 and 2.5 microM respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 microM.

The chemoprevention of spirulina platensis and garlic against diethylnitrosamine induced liver cancer in rats via amelioration of inflammatory cytokines expression and oxidative stress.

Natural antioxidant products play a vital role in the treatment and prevention of cancer disease because they have no side effects. This study aimed to compare the chemoprotective effect of Spirulina platensis (SP) and garlic against hepatocellular carcinoma (HCC) in rats. This study was being done by using 60 male Wistar rats and divided into four groups. Group (I): normal group. Group (II): HCC group induced by injection of a single dose of DEN (200 mg/kg/I.P) and after 14 days injected CCl4 (1 mg/kg/I.P) 3 times/week/six weeks. Group (III): HCC group received SP orally at a dose (500 mg/kg). Group (IV): HCC group received garlic (250 mg/kg) orally. The results revealed that the Spirulina and garlic treatment have a significant decrease in Glutamate pyruvate transaminase, Glutamate oxaloacetate transaminase, GGT, LDH, and the Malondialdehyde (MDA) activity, and furthermore, a significant increase in the total protein level, the superoxide dismutase (SOD), and Catalase (CAT) activity nearly to normal activity. Furthermore, the hepatic expression of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), inducible nitric oxide synthase, transforming growth factor-beta (TGF-ß1), Heat Shock Protein glycoprotein 96 (HSPgp96), and Glypican 3 (GP3) were down regulated by the Spirulina and garlic treatment in comparison with those in HCC group. All findings reported that the chemoprotective of both Spirulina and garlic that have nearly the same effect may be due to antioxidant activity and inhibition of lipid peroxidation, amelioration of pro-inflammatory cytokine, HSPgp96, and GP3.

Ameliorating Effect of Pineapple Juice on the Obesity-Induced Testicular Impairment in Male Wistar Rat.

<b>Background and Objective:</b> Obesity exerts negative influences on male reproductive capacity via changing the molecular and physical structure of male germ cells. This study was conducted to evaluate the mitigating effects of raw juice of pineapple on obesity-associated testicular impairment in male Wistar rats. <b>Materials and Methods:</b> Rats included the control group (G_I, n = 6) who received a Normal Diet (ND) and the obese group (G_II, n = 18) who received a High-Fat Diet (HFD). Obese rats (G_II) were subdivided into 3 groups (6 rats each): G_II represents the untreated obesity group that continued to receive HFD with plain Drinking Water (DW), G_III received ND along with raw juice (15% v/v) in DW and G_IV continued to receive HFD with raw juice (15% v/v) in DW. Rats were sacrificed at the end of the trial and testis was processed for histopathology and immunohistochemistry. <b>Results:</b> Testis from obese rats revealed a significant increment in spermatogenic cell degeneration, pro-inflammatory Nuclear factor of kappa B (NF-κB) and pro-apoptotic Caspase-3 immunoreactivities. Yet, Proliferating Cell Nuclear Antigen (PCNA) displayed poor immunoreactivity in obese rats' testis relative to controls. Administration of raw juice of pineapple to obese rats significantly reduced degeneration of spermatogenic cells, NF-κB and Caspase-3 immunoreactivities. Additionally, treatment with the juice significantly increased immunoreactivity to PCNA in obese rats. These ameliorating effects were more obvious in rats who received juice along with ND (G_III) than in those who received it along with HFD (G_IV). <b>Conclusion:</b> Treatment of obese rats with pineapple juice restored testicular homeostasis, indicating its potential validity to overcome obesity-induced male fertility disorders.

Field Evaluation of Native Fungus, Beauveria bassiana (Bals.) Vuillemin Against some Piercing-Sucking Insects on the Grapevine.

BACKGROUND AND OBJECTIVE: The Taify cultivar of grapevine (Vitis vinifera L.) is the second important economical fruit after pomegranate at high altitudes of the Taif region in Saudi Arabia. The grapevine trees are infested with different piercing-sucking insect pests especially aphids, whiteflies and thrips. The purpose of this study was to evaluate the ability of an indigenous endophytic entomopathogenic fungus, Beauveria bassiana to control the important piercing-sucking insect pests on grapevines. MATERIALS AND METHODS: This investigation was carried out through 5, 10 and 15 day intervals between sprays for controlling Aphis illinoisensis, Bemisia tabaci and Frankliniella occidentalis with a concentration of 6×106 conidia mL-1 under field conditions. RESULTS: The higher infestation in the untreated control was by aphids followed by whitefly and thrips. At the end of the experiment in the treated trees, aphid and whitefly reduction percentages with 5 day intervals of sprays (98.5 and 96.12%, respectively) were not significantly different from 10 day intervals (95.17 and 91.81%, respectively) while these reductions were significantly higher than the reduction occurred by 15 day intervals of sprays (65.93 and 44.51%, respectively). Meanwhile, the 3 intervals of sprays did not differ significantly in the thrips reduction occurred by them with a range from 93.62-96.46%. CONCLUSION: This indigenous B. bassiana as 6×106 conidia mL-1 with 10 day intervals of the spray-on grapevine can suppress the piercing-sucking insect pests. This also will participate in grapevine organic production and furthermore, it could replace the chemical treatment.

The modulatory effect of bee honey against diethyl nitrosamine and carbon tetrachloride instigated hepatocellular carcinoma in Wistar rats.

Hepatocellular carcinoma (HCC) is a serious threat to human health that has attracted substantial interest. The purpose of this study was to investigate the modulatory effect of bee honey against induced HCC by diethylnitrosamine/carbon tetrachloride (DEN/CCl4) in rats. HCC was induced by a single intraperitoneal dose of DEN (200 mg/kg B.W). Two weeks later, CCl4 (1 ml/kg) was intraperitoneally injected (three times a week). Bee honey was administered orally at 2 g/rat before and after the induction of HCC. The results showed that bee honey administration significantly increased body weight, decreased liver weight, and relative liver weight compared to those in the HCC-induced group. Moreover, a significant decrease in serum alpha-fetoprotein (AFP) as well as AST, ALT, GGT, ALP activities were observed in bee honey administration rats compared with those in HCC-induced group. Also, the hepatic MDA was significantly decreased; in addition, SOD, CAT, and GPx activities were significantly increased in groups treated with bee honey compared with those in the HCC group. The hepatic histopathology alterations caused by DEN/CCl4 injection were ameliorated by bee honey treatment. Likewise, the mRNA expression levels of tumor necrosis factor-alpha (TNF-α), transforming growth factor (TGF-ß1), intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), glypican (GP-3), thioredoxin (TRX), and glutaredoxin (GRX) were downregulated, and caspase-3 was upregulated by bee honey treatment compared with untreated HCC-induced group. In conclusion, bee honey has remarkable beneficial effects against HCC induced in rats through its antioxidant, anti-inflammatory, antifibrotic, and antimetastatic effects. PRACTICAL APPLICATIONS: The current study confirmed that honey has the potential to act as an antimetastatic factor. Bee honey supplementation either before or after combined injection of DEN/CCl4 exhibited inhibitory and ameliorative effects against DEN/CCl4-induced HCC through its antioxidant, antiproliferative, anti-metastatic, antifibrotic, and apoptosis properties. To our knowledge, this is the first study to describe the molecular mechanisms underlying honey's effects against DEN/CCl4-induced HCC in rats.

Antitumor and Antioxidant Activity of S-Methyl Methionine Sulfonium Chloride against Liver Cancer Induced in Wistar Albino Rats by Diethyl Nitrosamine and Carbon Tertrachloride.

Liver disease, especially liver cancer, has become a threat facing the world. Now, antioxidant products are garnering great attention for the treatment and prevention of many diseases. S-Methyl methionine sulfonium chloride (MMSC) is a methionine derivative and is present in many vegetables and has anti-inflammatory effects and antioxidants. This is the first study aiming to investigate the antitumor activity of the MMSC. This study was carried out on 60 male Wistar albino rats (4-6 weeks old age) and divided into four groups, with the first group as normal control, second group as hepatocarcinoma induced by diethyl nitrosamine and carbon tetrachloride (DEN/CCL4) group, third group as normal rats treated with MMSC, and fourth group as hepatocellular carcinoma (HCC) induced rats treated with MMSC. Our findings revealed that MMSC administration after HCC induction significantly improved (p < 0.05) the liver function biomarkers, including AST, GGT, albumin, globulin, and albumin/globulin ratio (A/G), in comparison with those in the HCC group. Moreover, the histopathological changes of the liver tissue in the HCC group were improved by MMSC treatment. Likewise, the expression levels of tumor necrosis factor-alpha (TNF-α), induced nitric oxide synthase (iNOS), transforming growth factor (TGF-1ß), and glypican 3 (GP3) were downregulated by MMSC treatment after HCC induction in comparison with those in the HCC-induced group. In conclusion, MMSC showed antitumor activity against HCC induction by DEN/CCl4 through decreasing lipid peroxide formation, the expression level of an inflammatory cytokines such as (TNF-α), immunoregulatory cytokines such as (TGF-1ß), induced nitric oxide synthase, and glypican 3.

Ginger Water Reduces Body Weight Gain and Improves Energy Expenditure in Rats.

Obesity is a serious global problem that causes predisposition to numerous serious diseases. The current study aims to investigate the effect of ginger water on body weight and energy expenditure through modulation of mRNA expression of carbohydrate and lipid metabolism. A white colored liquid obtained during freeze-drying of fresh rhizomes of Zingiber officinal was collected and named ginger water. It was used to treat rats, then blood and tissue samples were collected from the liver and white adipose at the end of the experiment. The serum was prepared and used for biochemical assays, while tissue samples were used for RNA isolation and gene expression analysis via Reverse transcription polymerase chain reaction (RT-PCR). Results of High Performance Liquid Chromatography (HPLC) analysis of ginger water revealed the presence of chrysin and galangin at concentrations of 0.24 µg/mL and 0.53 µg/mL, respectively. Average body weight gain decreased significantly in groups that received ginger water. In addition, both total cholesterol and serum triacylglycerol were reduced in the groups that received ginger water. Furthermore, mRNA expression of Sterol regulatory element-binding protein 1 (SREBP-1c) in the liver and leptin in adipose tissues were downregulated, while those of adiponectin, hepatic carnitine palmitoyltransferase1 (CPT-1), acyl-coA oxidase (ACO), Glucose transporter 2 (GLUT-2), and pyruvate kinase (PK) were upregulated in ginger water-treated groups. These results clearly revealed the lowering body weight gain effect of ginger water, which most likely occurs at the transcriptional level of energy metabolizing proteins.

Effect of Taraxacum officinale extract on PI3K/Akt pathway in DMBA-induced breast cancer in albino rats.

BACKGROUND: Breast cancer is one of the most prevalent types of cancer and a leading cause of death in women. MATERIALS AND METHODS: An experimental model of breast cancer was induced in female albino rats using single intragastric dose of 7, 12 dimethylbenz (α) anthracene (DMBA) in sesame oil (50 mg/kg b.wt). Four months after DMBA administration, incidence of breast cancer was confirmed by measuring cancer antigen 15-3 (CA15-3) serum levels. Taraxacum officinale ssp. officinale root extract (TOE) was administered in a dose of 500 mg/kg by oral gavage for 4 weeks after breast cancer incidence. Level of CA15-3 as one of the best known breast tumor markers was elevated in all positive breast cancer rats. The genetic effects of TOE on Pdk1-Akt1-Pik3r1-Map3k1-Erbb2-PIk3ca using semi-quantitative RT-PCR analysis were evaluated. In parallel, histopathological changes and immunohistochemical expression of Bcl2 in mammary gland tissues were examined. RESULTS: Level of CA15-3 was normalized in DMBA group administered TOE for 4 weeks. Administration of DMBA increased expression of Pdk1, Akt1, Pik3r1, Map3k1, Erbb2 and PIk3ca Treatment with TOE normalized the up-regulated mRNA for all examined genes except Pik3ra that was up-regulated. Mammary gland tissues of DMBA group showed excessive proliferation of lining epithelium of acini and ductules with hyperchromatic nuclei with excessive immunostaining of Bcl2 in the proliferated epithelium that was ameliorated by TOE administration. In conclusion, TOE regulated PI3K and Akt pathways involved in suppression of breast cancer growth and proliferation. TOE is effective as anticancer herbal agent.

Physiological and molecular study on the anti-obesity effects of pineapple (Ananas comosus) juice in male Wistar rat.

The present study was performed to assess anti-obesity effects of raw pineapple juice in high fat diet (HFD)-induced fatness. Based on food type, rats were divided into normal diet and HFD groups. When animals of HFD group become obese, they were given pineapple juice along with either HFD or normal diet. Blood biochemistry, liver and muscle gene expressions were analyzed. HFD induced significant elevations in body weight, body mass index (BMI), body fat accumulation, liver fat deposition and blood lipids while juice restored these parameters near to their normal values. Juice significantly decreased serum insulin and leptin while adiponectin was increased. Juice administration downregulated the increment of FAS and SERBP-1c mRNA expression in liver and upregulated HSL and GLUT-2 expressions. The muscular lipolytic CPT-1 expression was upregulted by juice treatment. Pineapple juice, therefore, may possibly be used as anti-obesity candidate where it decreased lipogenesis and increased lipolysis.

Down regulation of hepatic PPARalpha function by AhR ligand.

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates a spectrum of toxic and biological effects of 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and related compounds. Peroxisome proliferator activated receptor alpha (PPARalpha) is a nuclear receptor involved in the maintenance of lipid and glucose homeostasis. In this study we hypothesized that one of the possible mechanisms for the effect of TCDD and its related chemicals on fat metabolism could be through down regulation of PPARalpha functions. We treated Wistar rats with an AhR ligand, Sudan III (S.III), and/or PPARalpha ligand, Clofibric Acid (CA), for 3 days. We analysed the expression of one of the PPARalpha-target gene products, CYP4A protein and its mRNA. We also tested HepG2 cells with the afore-mentioned treatments and evaluated their effects on PPARalpha and RXRalpha protein. Treatment of Wistar rats with S.III was found to down regulates CYP4A protein expression and reduced its induction with CA. It also decreased mRNA expressions of CYP4A1, CYP4A2, CYP4A3 and PPARalpha. In HepG2 cells, PPARalpha and RXRalpha protein expression was decreased by S.III treatment in a dose dependent manner. Our results suggest that AhR has an inhibitory effect on PPARalpha function and a new pathway by which AhR ligands could disturb lipid metabolism.

Ethanolic extract of sharah, Plectranthus aegyptiacus, enhances healing of skin wound in rats.

Sharah, Plectranthus aegyptiacus (Forssk.) C. Chr. is a common native plant in the Taif region of Saudi Arabia. An ethanolic extract of freeze dried sharah leaves was added as 10% (w/w) to an ointment base of beeswax and sesame oil. The resultant ointment was examined as a potential enhancer of wound healing. Excision wounds in the nape region of the skin were induced in sixty albino Wistar rats. Animals were allocated in 4 groups (n=15) and kept individually in clean cages. The first group served as negative untreated controls without medication; the second group was treated with ointment base (vehicle); the third group represented the positive control and was treated with a reference ointment and the fourth one served as the experimental group and received the test plant extract (as ointment). Animal groups received the respective medications for 14 successive days. Wounds were measured and photographed every 3 days till the end of the experiment (day 21) in order to determine the wound closure rate (WCR). Specimens from wounds and surrounding skin were collected from sacrificed animals for histological and molecular studies. Both morphometric (based on WCR) and histological findings showed that the healing in animals treated with the sharah plant extract was better than those in control group or vehicle-treated group and was similar to that in the group that received the reference ointment. Moreover, the molecular findings concerning the expression levels of hepatocyte growth factor (HGF) and its receptor (c-Met) displayed a reasonable healing enhancing effect of the plant extract with the expression levels of both being higher in the extract-treated group than in the control group.

L-carnitine protects against testicular dysfunction caused by gamma irradiation in mice.

This study was conducted on mice to evaluate the radioprotective role of L-carnitine against γ-ray irradiation-induced testicular damage. Adult male mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure period either in the absence and/or presence of L-carnitine at an i.p. dose of 10 mg/kg body weight/day. Results revealed that γ-rays irradiation suppressed the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine prior and throughout γ-rays irradiation exposure inhibited this suppression. Treatment with γ-ray irradiation or L-carnitine down-regulated expression of aromatase mRNA. With combined treatment, L-carnitine significantly normalized aromatase expression. γ-Ray irradiation up-regulated expression of FasL and Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also showed that γ-ray-irradiation up-regulated TNF-α, IL1-ß and IFN-γ mRNA expressions compared to either controls or the L-carnitine treated group. Moreover, γ-irradiation greatly reduced serum testosterone levels, while L-carnitine, either alone or in combination with irradiation, significantly increased serum testosterone levels compared to controls. In addition, γ-irradiation induced high levels of sperm abnormalities (43%) which were decreased to 12% in the presence of L-carnitine. In parallel with these findings, histological examination showed that γ-irradiation induced severe tubular degenerative changes, which were reduced by L-carnitine pre-treatment. These results clarified the immunostimulatory effects of L-carnitine and its radioprotective role against testicular injury.

Identification of a new anti-diabetic agent by combining VOSO4 and vitamin E in a single molecule: studies on its spectral, thermal and pharmacological properties.

Vanadium(IV) complex of vitamin E (Vit E) ligand was reported. In this complex, binuclear ligand acts as a monodentate via oxygen of phenolic group. The vanadyl(II) ion is surrounded by two molecules of Vit E and two water molecules. The [VO(Vit E)(2)(H(2)O)(2)]2H(2)O complex was isolated by the reaction between VOSO(4) and vitamin E in ethanol/water solvent (50/50 w/w) at pH=8. The solid vanadyl(II) complex has been characterized by elemental analyses (CHN), photometric titrations, infrared spectra, molar conductivity, electronic spectra, TGA/DSC, SEM and XRD studies. Electronic and magnetic measurements are confirmed that the speculated geometry of vanadyl(II) complex is square pyramidal geometry. The microbial test was performed for the vanadyl complex against some kinds of bacteria and fungi. The [VO(Vit E)(2)(H(2)O)(2)]2H(2)O complex was proved effective in addressing diabetic of type I in case of experimental animal than other compounds were prepared in the literature.