Antioxidant therapies in attention deficit hyperactivity disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder among children and adults. Impulsivity, inattention, and hyperactivity are hallmark of ADHD. While ADHD is not on the autism spectrum, they are related in several ways as they have some overlapping symptoms. The pathogenesis of ADHD has so far remained enigmatic, however, there is some evidence suggesting critical association among ADHD and the level of oxidative stress which trigger cell membrane damage, changes in inner structure and function of proteins, as well as structural damage to DNA which eventually culminate into development of ADHD. Although stimulants as well as some classes of non-stimulants are used to ameliorate symptom of ADHD, various adverse effects have been associated with such compounds. To date, treatment of ADHD is done with a combination of medications, behavior modifications, psycho-education, family therapy and life-style changes. The American Academy of Pediatrics officially promote stimulant medications and/or behavior therapy as 'first line of therapy'. In addition to the presently therapeutic armamentarium, evidences are emerging on relevancy of natural products. There has been an interest on the therapeutic role of antioxidants in the treatment of ADHD. The present review aims to highlight the beneficiary role played by different antioxidants in mitigating the symptoms of ADHD.

Analysis of Tobacco-Specific Nitrosamines in the Common Smokeless Tobacco Afzal in Oman.

OBJECTIVES: There is a lack of awareness regarding the carcinogenicity of Afzal, an illegal smokeless tobacco product (STP) widely used among the Omani youth. Previous research has shown that certain types of tobacco-specific nitrosamines (TSNAs) are associated with oral and lung cancers. This study therefore aimed to assess levels of four common TSNAs in a randomly selected sample of Afzal. METHODS: This study was carried out at Sultan Qaboos University in Muscat, Oman, between April and September 2013. A random sample of Afzal was analysed for four types of TSNAs using high-performance liquid chromatography-tandem mass spectrometry. The four types of TSNAs analysed were 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosonornicotine (NNN), N-nitrosoanatabine (NAT) and N-nitrosoanabasine (NAB). As a reference product, a sample of laboratory-manufactured American moist snuff (Centers for Disease Control and Prevention, Atlanta, Georgia, USA) was also used to confirm the accuracy and precision of the analysis. RESULTS: The analysis revealed total TSNA levels of 3.573 µg/g in the Afzal sample. Mean levels of NNN, NNK, NAT and NAB were 1.205, 1.015, 0.809 and 0.545 µg/g, respectively. CONCLUSION: Levels of the two most abundant TSNAs (NNN and NNK) found in the Afzal sample exceeded international regulatory limits. Afzal users therefore need to be educated regarding the potential health risks associated with their STP use. Stricter implementation of current legislation is recommended to reduce the availability and usage of Afzal in Oman.

Solamargine triggers cellular necrosis selectively in different types of human melanoma cancer cells through extrinsic lysosomal mitochondrial death pathway.

BACKGROUND: Previous reports showed that the Steroidal Glycoalkaloid Solamargine inhibited proliferation of non-melanoma skin cancer cells. However, Solamargine was not tested systematically on different types of melanoma cells and was not simultaneously tested on normal cells either. In this study we aimed to investigate the effect of Solamargine and the mechanism involved in inhibiting the growth of different types of melanoma cells. METHODS: Solamargine effect was tested on normal cells and on another three melanoma cell lines. Vertical growth phase metastatic and primary melanoma cell lines WM239 and WM115, respectively and the radial growth phase benign melanoma cells WM35 were used. The half inhibitory concentration IC50 of Solamargine was determined using Alamarblue assay. The cellular and subcellular changes were assessed using light and Transmission Electron Microscope, respectively. The percentage of cells undergoing apoptosis and necrosis were measured using Flow cytometry. The different protein expression was detected and measured using western blotting. The efficacy of Solamargine was determined by performing the clonogenic assay. The data collected was analyzed statistically on the means of the triplicate of at least three independent repeated experiments using one-way ANOVA test for parametric data and Kruskal-Wallis for non-parametric data. Differences were considered significant when the P values were less than 0.05. RESULTS: Hereby, we demonstrate that Solamargine rapidly, selectively and effectively inhibited the growth of metastatic and primary melanoma cells WM239 and WM115 respectively, with minimum effect on normal and benign WM35 cells. Solamargine caused cellular necrosis to the two malignant melanoma cell lines (WM115, WM239), by rapid induction of lysosomal membrane permeabilization as confirmed by cathepsin B upregulation which triggered the extrinsic mitochondrial death pathway represented by the release of cytochrome c and upregulation of TNFR1. Solamargine disrupted the intrinsic apoptosis pathway as revealed by the down regulation of hILP/XIAP, resulting in caspase-3 cleavage, upregulation of Bcl-xL, and Bcl2, and down regulation of Apaf-1 and Bax in WM115 and WM239 cells only. Solamargine showed high efficacy in vitro particularly against the vertical growth phase melanoma cells. CONCLUSION: Our findings suggest that Solamargine is a promising anti-malignant melanoma drug which warrants further attention.

Characterisation of Nicotine and Cancer-Enhancing Anions in the Common Smokeless Tobacco Afzal in Oman.

OBJECTIVES: Afzal is a common smokeless tobacco product (STP) available illegally in Oman. This study aimed to assess pH and moisture levels and determine cancer-enhancing factors in a randomly selected sample of Afzal. METHODS: This study was carried out at the Sultan Qaboos University in Muscat, Oman, between April and December 2013. A package of Afzal was purchased from a single provider and divided into samples. The pH and moisture content of the samples were measured according to the protocols of the Centers for Disease Control and Prevention. Gas chromatography-mass spectrometry was used to analyse nicotine levels and ion-exchange chromatography (IC) was used to determine concentrations of nitrate, nitrite, chloride, fluoride, bromide, sulphate and phosphate anions. RESULTS: The samples had an alkaline pH of 10.46 with high levels of total (48,770.00 µg per g of STP [µg/g]) and unionised (48,590.00 µg/g) nicotine. The concentration of nitrate (8,792.20 µg/g) was alarmingly high. The chloride concentration (33,170.80 µg/g) showed a surge on IC chromatography. The moisture content percentage was 52.00%. CONCLUSION: The moisture content percentage and chloride concentration of Afzal was consistent with those of other STPs. In contrast, nitrite, sulphate and phosphate concentrations were below reported levels of other STPs. All anion concentrations were below the maximum daily limit set by international health organisations. However, the high concentrations of nitrite, nitrate and nicotine and the elevated alkaline pH observed in the analysed Afzal samples suggest that STP users will face health risks as a result of their use.