Maha H. Elamin

Bisphenol A Induces Hepatotoxicity through Oxidative Stress in Rat Model

Reactive oxygen species (ROS) are cytotoxic agents that lead to significant oxidative damage. Bisphenol A (BPA) is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to limited information concerning the effect of BPA on liver, this study investigates whether BPA causes hepatotoxicity by induction of oxidative stress in liver. Rats were divided into five groups: The first four groups, BPA (0.1, 1, 10, 50 mg/kg/day) were administrated orally to rats for four weeks. The fifth group was taken water with vehicle. The final body weights in the 0.1 mg group showed a significant decrease compared to control group. Significant decreased levels of reduced glutathione, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase activity were found in the 50 mg BPA group compared to control groups. High dose of BPA (50 mg/kg) significantly increased the biochemical levels of ALT, ALP and total bilirubin. BPA effect on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control. Data from this study demonstrate that BPA generate ROS and reduce the antioxidant gene expression that causes hepatotoxicity.

Curcumin inhibits the sonic hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells.

Medulloblastoma is an aggressive primary brain tumor that arises in the cerebellum of children and young adults. The Sonic Hedgehog (Shh) signaling pathway that plays important roles in the pathology of this aggressive disease is a promising therapeutic target. In the present report we have shown that curcumin has cytotoxic effects on medulloblastoma cells. Curcumin suppressed also cell proliferation and triggered cell‐cycle arrest at G2/M phase. Moreover, curcumin inhibited the Shh–Gli1 signaling pathway by downregulating the Shh protein and its most important downstream targets GLI1 and PTCH1. Furthermore, curcumin reduced the levels of β‐catenin, the activate/phosphorylated form of Akt and NF‐κB, which led to downregulating the three common key effectors, namely C‐myc, N‐myc, and Cyclin D1. Consequently, apoptosis was triggered by curcumin through the mitochondrial pathway via downregulation of Bcl‐2, a downstream anti‐apoptotic effector of the Shh signaling. Importantly, the resistant cells that exhibited no decrease in the levels of Shh and Bcl‐2, were sensitized to curcumin by the addition of the Shh antogonist, cyclopamine. Furthermore, we have shown that curcumin enhances the killing efficiency of nontoxic doses of cisplatin and γ‐rays. In addition, we present clear evidence that piperine, an enhancer of curcumin bioavailability in humans, potentiates the apoptotic effect of curcumin against medulloblastoma cells. This effect was mediated through strong downregulation of Bcl‐2. These results indicate that curcumin, a natural nontoxic compound, represents great promise as Shh‐targeted therapy for medulloblastomas.

Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells

Breast cancer constitutes a major health problem for women worldwide. However, its incidence varies between populations and geographical locations. These variations could be diet-related, since there are several carcinogenic compounds in the modern diet, while natural products contain various anti-cancer elements. Several lines of evidence indicate that, in addition to their clear preventive effect, these compounds could also be used as therapeutic agents. In the present report we have shown that oleuropein, a pharmacologically safe natural product of olive leaf, has potent anti-breast cancer properties. Indeed, oleuropein exhibits specific cytotoxicity against breast cancer cells, with higher effect on the basal-like MDA-MB-231 cells than on the luminal MCF-7 cells. This effect is mediated through the induction of apoptosis via the mitochondrial pathway. Moreover, oleuropein inhibits cell proliferation by delaying the cell cycle at S phase and up-regulated the cyclin-dependent inhibitor p21. Furthermore, oleuropein inhibited the anti-apoptosis and pro-proliferation protein NF-κB and its main oncogenic target cyclin D1. This inhibition could explain the great effect of oleuropein on cell proliferation and cell death of breast cancer cells. Therefore, oleuropein warrants further investigations to prove its utility in preventing/treating breast cancer, especially the less-responsive basal-like type.

Oleuropein induces apoptosis via the p53 pathway in breast cancer cells.

BACKGROUND Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. MATERIALS AND METHODS p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. RESULTS Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. CONCLUSIONS Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.

Oleuropein Induces Anti-metastatic Effects in Breast Cancer

Breast cancer causes death due to distant metastases in which tumor cells produce matrix metalloproteinase (MMP) enzymes which facilitate invasion. Oleuropein, the main olive oil polyphenol, has anti-proliferative effects. This study aimed to investigate the effect of oleuropein on the metastatic and anti-metastatic gene expression in the MDA human breast cancer cell line. We evaluated the MMPs and TIMPs gene expression by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in treated and untreated cells. This study demonstrated that OL may induce anti-metastatic effects on human breast cancer cells. We found that TIMP1,-3, and -4 were over-expressed after all periods of incubation in treated cancer cells compared to untreated cells, while MMP2 and MMP9 genes were down-regulated, at least initially. Treatment of breast cancer cells with oleuropein could help in prevention of cancer metastasis by increasing the TIMPs and suppressing the MMPs gene expressions.

Prevalence and genotyping of Toxoplasma gondii among Saudi pregnant women in Saudi Arabia

Introduction: Toxoplasma gondii (T. gondii) is an intracellular protozoan that can infect all mammals, who serve as intermediate host. It causes congenital, neurological, eyes complications and mild or asymptomatic infections in humans. Purpose of this study: To investigate not only the prevalence of T. gondii, but also to find out its genotyping using multiple sequential molecular methods to predict exactly the precise genotyping of T. gondii among Saudi pregnant women. Methods: A cross-sectional study was conducted using multi-stage methods. Initial stage involved enrolment of 250 Saudi pregnant women from multi-centre healthcare and community based settings in the capital of Saudi Arabia Riyadh. The second stage was embracement of the laboratory investigation that included Enzyme immunoassay (ELISA), DNA extraction, PCR, nested-PCR assay, and genotyping of the seropositive cases. Results: 203 women agreed to take part in our study with a response rate of 81.2% (203/250). Using ELISA, we found that the prevalence of Toxoplasma gondii IgG and IgM antibodies was 32.5% and 6.4%, respectively. We found that 29 samples (80.6%) were of genotype II; however 7 samples (19.4%) were of genotype III. Conclusion: Defining the population structure of T. gondii from Saudi Arabia has important implications for transmission, immunogenicity, pathogenesis, and in planning preventive strategies. Relationship between such variation in structure and disease manifestation in pregnant women is still difficult to assess due to the role of host immune status and genetic background on the control of infection, and of other parasitic features such as the infecting dose or parasite stage. Our finding of the genotyping of T. gondii might facilitate and inform future studies on comparative genomics and identification of genes that control important biological phenotypes including pathogenesis and transmission among Saudi women.

Leishmanicidal and apoptotic activities of oleuropein on Leishmania major.

BACKGROUND Leishmania is a unicellular protozoan parasite causing a wide range of human diseases ranging from localized self-healing cutaneous lesions to fatal visceral infections. OBJECTIVE The aim of the present study is to assess the cytotoxic, anti-proliferative, and apoptotic effects of oleuropein on Leishmania major promastigotes (MHOM/SA/84/JISH) and to compare its effects with the reference drug sodium stibogluconate (pentostam). METHODS Cytotoxicity and promastigote proliferation were measured using MTT colorimetric assay. Furthermore, the Annexin V/propidium iodide staining technique followed by flow cytometry was used for studying the cell death properties of oleuropein. RESULTS In the present report we have shown that oleuropein, a pharmacologically safe, natural product of olive leaf, has a potent leishmanicidal effect. Indeed, oleuropein exhibits cytotoxic and anti-proliferative effects against Leishmania major promastigotes. Moreover, oleuropein triggers death through apoptosis, whereas pentostam induces death mainly via necrosis on Leishmania major promastigotes. CONCLUSION Here we demonstrate for the first time that the non-toxic, natural product oleuropein has apoptotic properties against Leishmania major promastigotes. Further studies are needed to investigate its molecular pathway.

Genotyping of Toxoplasma gondii from rats (Rattus rattus) in Riyadh, Saudi Arabia.

Toxoplasma 3 main clonal lineages are designated as type I, II, and III; however, atypical and mixed genotypes were also reported. This study was conducted for detection of Toxoplasma gondii genotypes in rats (Rattus rattus) in Riyadh region, Saudi Arabia. PCR test on T. gondii B1 gene was conducted on ELISA IgM positive samples for confirmation of the infection. However, genetic analysis of the SAG2 locus was performed to determine T. gondii genotypes using PCR-RFLP technique. PCR test on T. gondii B1gene showed that 22 (81.5%) out of the 27 ELISA IgM positive samples have T. gondii DNA. Genotypic analysis shows that, of the total 22 PCR positive samples, only 13 (59.1%) were of type II, 7 (31.8%) were of type III, and 2 (9.1%) were of an unknown genotype. It is obvious that the prevalence of both type II and III is high in rats. No reports have been available on T. gondii genotypes among rats in Riyadh region, and only little is known about its seroprevalence in rats. Future studies on T. gondii genotypes in rats using multi-locus markers is needed in Riyadh region, Saudi Arabia for better understanding of T. gondii pathogenesis and treatment in humans and animals.

Evidence for persistence and a major range extension of the smooth-coated otter (Lutrogale perspicillata maxwelli; Mustelidae, Carnivora) in Iraq

Abstract. The species IUCN conservation status of smooth-coated otter (Lutrogale perspicillata) is considered ‘Vulnerable’, due to an inferred future population decline caused by habitat loss and sustained exploitation. The status of the Arabian subspecies (L. p. maxwelli) occurring in the Tigris marshes of Iraq and Iran is uncertain due to political problems and limited access to this border region in recent years. With this study we could confirm the persistence of the smooth-coated otter in the marshlands of southern Iraq by using a mitochondrial marker (cytochrome b). Moreover, a second sample from Kurdistan was also identified to be L. perspicillata. This observation represents a major range extension of more than 500 km for this poorly known species. It is recommended to undertake further surveys of suitable habitat in the Tigris wetlands, as well as in Kurdistan, to obtain additional information on the distribution of smooth-coated otter in Iraq, and implement conservation measures in those areas.

Experimental Cassia senna intoxication in Lohmann broiler chicks

The aim of this study was to evaluate the toxic effects of Cassia senna fruits in Lohman broiler chicks. Chicks fed with diet containing 2 and 5% C. senna fruit for 4 weeks, thereafter the chicks in the two groups were fed with control diet for 2 weeks. Depression in body weight, weight gain, inefficiency of feed utilization and anaemia was observed in chicks fed with 2 and 5% C. senna compared with the control diet. There were significant increase in the serum values of sorbitol dehydrogenase, lactate dehyrogenase, glutamate dehydrogenase, glutmate oxaloacetate transaminase, acid phosphatase uric acid and significant decrease in the blood values of haemoglobin concentration (Hb), packed cell volume (PCV) and red blood corpuscle (RBC) in test chicks were compared to those of the control group. Liver showed vacuolation of the centrilobular hapatocytes in the two groups. Kidneys showed degeneration and or necrosis of the epithelial cells of the tubules, scattered lymphoid nodules and shrinkage of the glomerular tufts. Catarrhal enteritis and focal degeneration of the intestinal mucosa were observed in test groups. At the end of the period following withdrawal of senna meals the damage to the vital organs was reduced but neither the hepatocytes nor the cells of the renal tubules had completely reverted to normal.