Abeer Al-Dbass

Measurement of selected ions related to oxidative stress and energy metabolism in Saudi autistic children

OBJECTIVES Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to clarify the role of selected ions related to energy metabolism as a consequence of oxidative stress in the deterioration accompanied autism. MATERIALS AND METHODS Malonaldehyde as measure of lipid peroxidation, Na(+)/K(+) ion pump (ATPase), together with the concentrations of Na(+), K(+), Mg(2+), Ca(2+) and Pb(2+) were determined in plasma of 30 Saudi autistic patients and compared to 30 age-matching control samples. RESULTS The obtained data recorded that Saudi autistic patients have a remarkable higher activities of Na(+)/K(+) ATPase and high levels of lipid peroxidation compared to control. In addition, they have significantly elevated levels of K(+) and Pb(2+) while Ca(2+) recorded a significantly lower level compared to age-matching control subjects. On the other hand both Mg(2+) and Na(+) were non-significantly changed in autistic patients. CONCLUSION Alteration of the selected measured ions confirms that oxidative stress and defective mitochondrial energy production could represent the primary causative factor in the pathogenesis of autism.

Role of Different Natural Antioxidants in the Modulation of mRNA-expression of Apoptotic Molecules in the Livers of Carbon Tetrachloride-Intoxicated Rats

ABSTRACT Overexpression of nuclear factor (NF-κB) or activation of Smad3 by transforming growth factor β (TGF-β1) induced by oncogenes results in overexpression of fibrotic processes and hence cell death. The objective of this study is to examine whether Silymarin (Sil) alone or in combination with Vitamin E (Vit E) and/or Curcumin (Cur) plays a modulatory role against the overexpression of NF-κB, and TGF-β that induced in response to carbon tetrachloride (CCl4) administration. The present work revealed that CCl4 induced elevation of in serum alanine aminotransferase (ALT), Apoptosis regulator (Bax), Smad3, TGF-β, and NF-kB hepatic mRNA expression (using Real-time PCR), administration of Sil alone downregulated these expressions. Treatment with Vit E acid and/ or Cur along with Sil produced best results in this concern. B-cell lymphoma 2 (Bcl-2) expressions were downregulated by CCl4; whereas concurrent treatment of Vit E and/or Cur along with Sil increased its expression. On conclusion, the use of Vit E and/or Cur could potentiate the antiapoptotic action of Sil.

Neuroprotective effect of creatine against propionic acid toxicity in neuroblastoma SH-SY5Y cells in culture

This work aimed to verify propionic acid toxic effects, and to investigate the possible neuroprotective effects of creatine against it. Propionic acid (PA) toxicity together with the effect of creatine (CR) was studied on neuroblastoma SH-SY5Y brain cells in culture. In the first group, cells were divided and treated with different concentrations of PA, while the second group was pre-treated with creatine to test its neuroprotective effect in PA-intoxicated cells. Comet assay and DNA fragmentation studies were used to examine genotoxicity and apoptosis of cells. The results emphasized the neurotoxicity of propionate to neuroblastoma cell line SH-SY5Y by DNA fragmentation that increased in a dose- and time-dependent manner. More importantly, our data confirms a possible neuroprotective effect of creatine against the neurotoxic effect of propionic acid. The obtained in vitro data supports and explains the in vivo neurotoxic effect of PA and proves its DNA damaging effect which could clarify its role in the etiology of autism, a phenomenon recently raised by many researchers. It also supported the accumulating literature which describes creatine as a potential bioactive agent against neurotoxicity. With sufficient research and clinical trials in future, this could prove to be successful in treatment or management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity.

The expression of telomere-related proteins and DNA damage response and their association with telomere length in colorectal cancer in Saudi patients

Background Colorectal cancer is the leading cause of cancer-related deaths in Saudi Arabia. Cancer has a multifactorial nature and can be described as a disease of altered gene expression. The profiling of gene expression has been used to identify cancer subtypes and to predict patients’ responsiveness. Telomere-associated proteins that regulate telomere biology are essential molecules in cancer development. Thus, the present study examined their contributions to colorectal cancer progression in Saudi patients. Methods The expression of hTERT, TRF1, TRF2, POT1, ATR, ATM, Chk1 and Chk2 were measured via real-time PCR in matched cancerous and adjacent tissues of CRC patients. The protein level of hTERT, TRF1, TRF2, ATR, ATM, Chk1 and Chk2 were measured using immunohistochemistry. A region of hTERT core promoter was sequenced via Sanger sequencing. Methylation of CTCF binding site was examined via methylation-specific PCR. Finally, the length of telomere was estimated using q-PCR. Results Our results showed that POT1, ATR, Chk1 and Chk2 show increased expression in CRC relative to the adjacent mucosa. The expression levels of each gene were associated with clinicopathological characteristics of patients with CRC. There was a positive correlation between the age of the patients and hTERT expression. Regarding tumor site, telomere length, ATR, ATM and Chk1 were shown to be altered. No somatic mutation was detected in hTERT core promoter, and no differences in methylation patterns at CTCF binding site in the promoter between normal and cancer tissues. Conclusion Analysis of targeted genes expression in colorectal cancer based on the clinical variables revealed that tumor location and age could have a role in gene expression and telomere length variations and this could be taken under consideration during CRC diagnosis and therapy. Other epigenetic mechanisms could influence hTERT expression in cancers. Our findings warrant further validation through experiments involving a larger number of patients.

High-fat diet stimulates the gut pathogenic microbiota and maintains hepatic injury in antibiotic-treated rats

The gut and the liver are closely linked to each other, as changes in the gut microbiota can play a significant role in the development of many liver diseases. Gut bacteria respond rapidly to changes in diet and thus can affect the liver through their metabolites. The impact of a high lipid diet on the liver in the presence of an altered gut flora modulated by ampicillin was investigated. The study was performed on 30 male Western albino rats randomly divided into 3 groups: control (phosphate buffered saline treated), group II (ampicillin 50 mg/kg for three weeks to induce microbiota alterations and fed on standard diet) and group III (same dose of ampicillin and fed on a lipid rich diet). Stool samples were collected for qualitative determination of bacteria. Serum hepato-specific markers, in addition to Glutathione (GSH), Lipid peroxidase (MDA), Glutathione-S- transferase(GST), and vitamin C in liver tissues, were measured. Altered gut microbiota significantly increased the level of the hepato-specific marker MDA and reduced the GST, GSH and vitamin C levels. However, animals fed a lipid rich diet displayed a more significant shift in hepatic markers and antioxidants. Moreover, a new switch in composition of the gut bacteria was observed by feeding the lipid rich diet. Our study showed that bacterial overgrowth in the gut can be associated with liver dysfunction and that a high lipid diet can promote the overgrowth of some liver damaging microflora during antibiotic treatment.