On the Toxicity of Therapeutically Used Nanoparticles: An Overview

Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. The rapidly developing field of nanotechnology will result in new sources of this exposure, through inhalation, ingestion, and injection. Although nanomaterials are currently being widely used in modern technology, there is a serious lack of information concerning the human health and environmental implications of manufactured nanomaterials. Since these are relatively new particles, it is necessary to investigate their toxicological behavior. The objective of this review was to trace the cellular response to nanosized particle exposure. Therapeutic application of selected nanoparticles together with their range of toxic doses was also reviewed. Effect of therapeutically used nanoparticles on cell membrane, mitochondrial function, prooxidant/antioxidant status, enzyme leakage, DNA, and other biochemical endpoints was elucidated. This paper highlights the need for caution during the use and disposal of such manufactured nanomaterials to prevent unintended environmental impacts

Is consanguinity prevalence decreasing in Saudis?: A study in two generations

Background: Saudi population is unique in that there is a strong  preference for cousin marriages in the general population. We studied the prevalence of consanguinity in educated Saudi females and compared the results with the results obtained in their parents, to access if a generation difference in which extensive educational activities have prevailed to inform the people of the influence of cousin marriages on health, has made any difference in prevalence of consanguineous marriages.Method: A total of 600 Saudi women (421 university students and 179 women attending outpatients’ clinics) were interviewed about their own and their parents’ consanguinity.Results: The total consanguinity (first and second cousins) was 29.7% in the parents. Consanguinity was significantly higher among the daughters than the parents, where 37.9% of the 293 married women had  consanguineous marriages. The prevalence of consanguinity was studied in different age groups, though no significant pattern was observed. A strong correlation was found between consanguinity of parents and their  daughters; consanguinity was highest (52.3%) in the daughters of parents who were themselves consanguineous.Conclusion: The results did not reveal any decrease in the prevalence of consanguinity over a generation. This shows that the tradition of marrying within the family is a preferred practice, despite the awareness that certain genetic disorders occur at a higher frequency in cousin marriages. There is a need at the primary health care level to inform the public of the consequences of this common practice.Key words: Consanguinity; Saudis; First cousin marriage; second cousin marriage; Middle East

Elimination of high-refined-sugar diet as treatment strategy for autistic features induced in a rodent model

Purpose: To investigate the potency of ampicillin in altering gut flora in the presence of a high-sucrose diet in rat pups, and to determine its effect on selected neurotransmitters and a cytokine as markers of the persistent autistic features repeatedly induced in orally administered propionic acid rat pups..Methods: Twenty-eight young male Wistar albino rats were divided into four equal groups. The first group served as a control. The second group received an oral neurotoxic dose of propionic acid (PPA, 250 mg/kg body weight/day) for 3 days. The third group was treated with ampicillin (50 mg/kg for 3 weeks) with a standard diet. The fourth group was given the same dose of ampicillin with a high-sucrose diet for 10 weeks.Results: The results showed a significant (p < 0.001) decrease in the investigated neurotransmitters in PPA- and ampicillin-treated rat pups (norepinephrine by 32.49 and 14.58 %, dopamine by 31.45 and 20.22 %, serotonin by 35.99 and 29.09 %), as well as a remarkable increase (p < 0.001) in the proinflammatory cytokine, IL-6 (30.07and 6.07 %). The high-sucrose diet also significantly (p < 0.001) enhanced the neurotoxic effect of ampicillin.Conclusion: The observed dietary modulation of the gut microbiota, coupled with the subsequent modulation of brain neurochemistry and inflammation, demonstrates the considerable potential of dietary intervention through the elimination of highly refined sugar as a treatment strategy to prevent and treat autism.Keywords: Neurotoxicity, Ampicillin, Propionic acid, Neurotransmitters, Cytokines, High-sucrose die

Activities of key glycolytic enzymes in the plasma of Saudi autistic patients

A El-Ansary1, S Al-Daihan1, A Al-Dabas1, L Al-Ayadhi21Biochemistry Department, Science College, 2Autism Research and Treatment Unit, Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi ArabiaObjective: Measurement of plasma levels of lactate, lactate oxidase (LOX), pyruvate kinase (PK), and hexokinase (HK) as possible glycolytic parameters to assess brain damage in autistic patients.Design and methods: Plasmatic levels of lactate, LOX, PK, and HK were determined in 20 autistic children aged 3–15 years and 20 age-matching healthy control subjects.Results: Plasmatic levels of lactate and LOX were significantly higher in autistic patients compared to healthy subjects and that of PK and HK were significantly lower in these patients as compared to controls. This could reflect the impaired metabolism of astrocytes, the brain cells responsible for the production and provision of lactate, as the primary metabolic fuel for neurons.Conclusion: Remarkably different levels of plasma glycolytic parameters were recorded in Saudi autistic patients. This could be correlated to the impairment of energy metabolism, glutathione depletion, and lead intoxication previously detected in the same investigated samples. The identification of biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention.Keywords: autism, glycolysis, lactate, lactate oxidase, pyruvate kinase, hexokinas

The effect of a sublethal concentration of Solanum nigrum on some antioxidants in Biomphalaria arabica

Schistosomisis is endemic in many rural areas of developing countries. The life cycle of schistosomes is complex with two hosts, an intermediate snail host and a definitive human host. Biomphalaria arabica is the intermediate host for Schistosoma mansoni in Saudi Arabia. One method of controlling the disease is to break the life cycle at the intermediate host snail stage using molluscicides. Snails kill schistosomes by a mechanism involving production of reactive oxygen species. In this study malondialdehyde (MDA), and the antioxidants glutathione (GSH), catalase (CAT) and glutathione peroxidase (GP(x)) were determined in tissue homogenates of B. arabica treated with sublethal concentration (LC25) of the plant molluscicide Solanum nigrum. MDA, GSH and CAT were significantly increased in molluscicide-treated snails compared to controls (p < 0.000). GP(x) was decreased in treated snails. It therefore appears that a sublethal concentration of S. nigrum increases both ability of snail tissue to generate cytotoxic ROS and antioxidants for protection of the tissue against the cytotoxicity. The increase in the level of ROS would decrease snail- schistosome compatibility.King Saud Universit

CYP19A1 gene polymorphism and colorectal cancer etiology in Saudi population: case&ndash;control study

Fatimah Basil Al-Mukaynizi,1 Mohammed Alanazi,1 Sooad Al-Daihan,1 Narasimha Reddy Parine,1 Majid Almadi,2 Abdulrahman Aljebreen,2 Nahla Azzam,2 Othman Alharbi,2 Maha Arafah,3 Arjumand Warsy4 1Department of Biochemistry, College of Science, 2Department of Internal Medicine, 3Department of Pathology, College of Medicine, 4Central Laboratory, Female Center for Scientific &amp; Medical Colleges, King Saud University, Riyadh, Saudi Arabia Background: Considerable interest is directed toward the enzyme aromatase (CYP19A1) and the development of cancer, due to CYP19A1&rsquo;s role in estrogen biosynthesis. Several cancers display excessive intra-tumor accumulation of estrogens, and aromatase inhibitors are used for treatment. The CYP19A1 gene exhibits polymorphism and mutations that can alter its expression or aromatase activity and influence estrogen production. We designed this study to investigate the link between CYP19A1 polymorphism and susceptibility to colorectal cancer (CRC) development in Saudis. Patients and methods: Blood samples from 100 CRC patients and 100 healthy controls were drawn for DNA extractions. Three polymorphic sites, rs4774585, rs936308, and rs4775936, were genotyped using Taqman genotyping by real-time polymerase chain reaction. Allelic and genotype frequencies were calculated and compared in the two groups. Results: All single nucleotide polymorphisms (SNPs) were polymorphic in Saudis, and comparison of allele frequencies showed several differences when compared to other populations. None of the SNPs were associated with the risk of CRC development in Saudis (P&gt;0.05). Some gender and location (colon or rectal) differences were observed. Discussion: The results of this study highlighted the genetic heterogeneity existing between populations in the prevalence of different SNPs and their relation to disease state. It showed that, although rs4774585, rs936308, and rs4775936 are involved in CRC development in several populations, their role is not significant in the etiology of CRC in Saudis; however, some SNPs do increase susceptibility or resistance to CRC development as judged from the odds ratio. Further large-scale studies are warranted to clarify the role of the CYP19A1 development in CRC. Keywords: aromatase, CYP19A gene, polymorphism, SNPs, colorectal cancer, rs4774585, rs936308, rs477593

TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

Breast cancer remains a worldwide public health concern. The incidence and mortality of breast cancer varies significantly in ethnically and geographically distinct popula-tions. In the Kingdom of Saudi Arabia (KSA) breast cancer has shown an increase in incidence and is characterized by early onset and aggressiveness. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. Furthermore, studies have shown a correla¬tion between certain p53 mutations and response to therapy in breast cancer. In the present study, TP53 mutations were identified by direct sequencing of the gene (exons 4-9) from 119 breast cancer tissues. The prevalence of TP53 mutations in Arab breast cancer patients living in the KSA is among the highest in the world (40%). Notably, 73% of the patients whose tumors harbored p53 mutations were less than 50 years of age. Furthermore, for the first time, we identified 7 novel mutations and 16 mutations in breast cancer tissues. Notably, all the novel point mutations were found in exon 4, wherein 29% of the mutations were localized. Furthermore, an excess of G:C→A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. The results indicate that the TP53 gene plays a significant role in breast carcinogenesis and the early onset of the disease among Arab female individuals.King Saud Universit