Molecularly Tracing of Children Exposure Pathways to Environmental Persistent Organic Pollutants and the Autism Spectrum Disorder Risk

Organic pollutants (OPs) including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) have showed neuro-damaging effects, but studies concerning the autism spectrum disorder (ASD) risk are limited. A case-control study with ASD (n=125) and healthy control (n=125) children was conducted on the different land use settings across Punjab, Pakistan. Serum concentrations of 26 OCPs, 29 PCB congeners, 11 PBDEs and 32 PAHs were measured. Serum PCB77 (AOR = 2.00; 95% CI: 1.43, 2.18), PCB118 (AOR = 1.49; 95% CI: 1.00, 2.00), PCB128 (AOR = 1.65; 95% CI: 1.01, 1.91), PCB153 (AOR = 1.80; 95% CI: 1.55, 1.93) were significantly higher, but PCB187 (AOR = 0.37; 95% CI: 0.24, 0.49) was significantly lower in the ASD cases when compared to the controls. Serum BDE99 (AOR = 0.48; 95% CI: 0.26, 0.89) was significantly higher in the healthy controls than in the ASD cases. Among the analysed OCPs, p,p′-DDE (AOR = 1.50; 95% CI: 1.00, 1.85) was significantly elevated in the ASD cases with comparison in the controls. For PAHs, serum dibenzothiophene (AOR = 7.30; 95% CI: 1.49, 35.85) was significantly higher in the ASD, while perylene (AOR = 0.25; 95% CI: 0.06, 1.10) and fluorene (AOR = 0.21; 95% CI: 0.06, 0.72) were significantly higher in the controls. In addition, many of the serum pollutants were significantly associated with GSTT1, GSTM1 (null/present polymorphism) and presented the genotypic variation to respond xenobiotics in children. The children living in proximity to urban and industrial areas had a greater exposure to most of the studied pollutants when compared to the rural children, however children residing in rural areas showed higher exposure to OCPs. This comprehensive study documents an association between environmental exposure risk of several organic pollutants (OPs) from some contaminated environmental settings with ASD risk in children from Pakistan

Acrylamide-induced testicular toxicity in rat: modulatory effect of 5-aminosalicylic acid

Acrylamide (AA) is a vinyl monomer that has many applications in chemical industries. The aim of this work was to assess the reproductive toxicity of AA and clarity its underlying mechanism of action in rat; in particular, whether AA or its reactive metabolite glycidamide is responsible for the majority of the noted adverse effects. Moreover, the protective effect of 5-aminosalicylic acid (5-ASA) against AA testicular and genotoxicity was investigated. Acrylamide gavaged at doses from 5-60mg/kg daily for 5 consecutive days caused dose- dependent toxicity. Light microscopy examination showed multinucleated giant cells and tubular atrophy in the testis. In addition, electron microscopy showed Leydig cell atrophy and Sertoli cell toxicity. Epididymal sperm count showed a significant reduction in caudal sperm count in particular at higher concentrations. Despite these microscopic effects on the testis, this work also showed that AA has no toxic effects on absolute or relative testis or cauda weight, and no toxic effect on seminiferous tubule diameter. Outside of the testis, COMET assay undertaken on peripheral blood leukocytes showed genotoxicity in the form of COMET cells with increased Tail moment, while ELISA of serum testosterone showed severe reduction in testosterone level after AA treatment, which was reversed by concomitant ASA treatment. ELISA of CYP2El showed a 2-fold higher concentration in control liver S9 when compared to control testis S9. Further, 5-ASA (50mg/kg) induced the level of liver CYP2El, potentially increasing AA metabolism and clearance; this induction was accompanied by an improvement of testicular pathology and reduction in COMET Tail moments. Together, these data are consistent with AA being the main causative agent responsible for the toxicity noted in the testis and genotoxicity in blood. Moreover, 5-ASA could potentially offer a protective mechanism against AA- mediated toxicity, by increasing AA clearance. In conclusion, at the used dose, AA caused toxic effects in male rat that can be reduced by concomitant treatment with 5-ASA, which might be considered as an antidote to AA toxicity in victims of AA poisoning.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Acrylamide-Induced Testicular Toxicity in Rat: Modulatory Effect of 5-Aminosalicylic Acid.

Acrylamide (AA) is a vinyl monomer that has many applications in chemical industries. The aim of this work was to assess the reproductive toxicity of AA and clarify its underlying mechanism of action in rat; in particular, whether AA or its reactive metabolite glycidamide is responsible for the majority of the noted adverse effects. Moreover, the protective effect of 5-aminosalicylic acid (5-ASA) against AA testicular and genotoxicity was investigated. Acrylamide gavaged at doses from 5-60mg/kg daily for 5 consecutive days caused dose-dependent toxicity. Light microscopy examination showed multinucleated giant cells and tubular atrophy in the testis. In addition, electron microscopy showed Leydig cell atrophy and Sertoli cell toxicity. Epididymal sperm count showed a significant reduction in caudal sperm count in particular at higher concentrations. Despite these microscopic effects on the testis, this work also showed that AA has no toxic effects on absolute or relative testis or cauda weight, and no toxic effect on seminiferous tubule diameter. Outside of the testis, COMET assay undertaken on peripheral blood leukocytes showed genotoxicity in the form of COMET cells with increased Tail moment, while ELISA of serum testosterone showed severe reduction in testosterone level after AA treatment, which was reversed by concomitant ASA treatment. ELISA of CYP2E1 showed a 2-fold higher concentration in control liver S9 when compared to control testis S9. Further, 5-ASA (50mg/kg) induced the level of liver CYP2E1, potentially increasing AA metabolism and clearance; this induction was accompanied by an improvement of testicular pathology and reduction in COMET Tail moments. Together, these data are consistent with AA being the main causative agent responsible for the toxicity noted in the testis and genotoxicity in blood. Moreover, 5-ASA could potentially offer a protective mechanism against AA-mediated toxicity, by increasing AA clearance. In conclusion, at the used dose, AA caused toxic effects in male rat that can be reduced by concomitant treatment with 5-ASA, which might be considered as an antidote to AA toxicity in victims of AA poisoning

Effect of the combined administration of vitamin-E and 5-aminosalicylic acid on acrylamide-induced testicular toxicity

Objectives: This study aimed to evaluate the comparative protective antioxidant effect of 5-aminosalicylic acid (5-ASA) and vitamin-E against acrylamide (ACR)-induced testicular toxicity in rats. Methods: This study was performed at King Fahad Medical Research Centre, Jeddah, KSA. A total of 49 adult Wistar rats (250 ± 20 gm) that were 60 days old were divided into seven groups (control, ACR alone, ACR + 5-ASA, ACR + Vitamin-E, ACR + 5-ASA + Vitamin-E, Vitamin-E alone, 5-ASA alone). Acrylamide [45 mg/kg (bw)/day] and vitamin-E [200 mg/kg (bw)/day] were gavaged orally, and 5-ASA [25 mg/kg (bw)/day] were injected intra-peritoneally for five consecutive days after one day of observation. Rats were sacrificed by cervical dislocation. Histopathology of the testis, enzyme linked immunosorbent assay (ELISA) of testosterone, the lactate dehydrogenase (LDH) assay and a caudal sperm count were performed. Results: Rats treated with ACR showed signs of aggression and rough coats, with reduced food and water intake. ACR treated rats showed histopathological changes in the form of a sloughed seminiferous epithelium in the tubular lumen with no multinucleated giant cells. Shrinkage of seminiferous tubules with widening of the interstitial space was also observed with atrophy and the shedding of normal mucosa. Our results indicated that maximum protection was conveyed by the combined antioxidant effect of vitamin-E and 5-ASA on testicular histopathology. Conclusion: We conclude that acrylamide-induced degeneration of seminiferous tubules can be partially reversed by the administration of 5-ASA and vitamin-E and suggests restricting exposure to ACR

Antioxidant effect of <em>Ferula hermonis</em> Boiss on acrylamide induced testicular toxicity in male rats

138-144Acrylamide (ACR) is potentially carcinogenic to humans. It is also a food toxicant, geno-neuro and reproductive toxicant to wide variety of laboratory animals. ACR stimulates release of free radicals, which cause oxidative stress inducing many toxic effects in body, particularly testis. Antioxidants are known to decrease the toxic effect of ACR and Ferula hermonis Boiss root extract is a known natural antioxidant. This study investigates the antioxidant effect of Ferula sp. root extract on acrylamide induced testicular toxicity in male rats. Sixteen adult male virgin Wister rats were used and divided into four groups (control, ACR, ACR+Ferula sp., Ferula sp.). Histopathological studies for the right testis and caudal sperm count were carried out. Significant reduction in sperm count and testosterone serum level was found in ACR treated group. However, histopathological study did not show significant difference between ACR and ACR+Ferula sp. groups. ACR produced histopathological changes in testes and liver of rats. Ferula sp. root extract can be used as a weak antioxidant against ACR induced testicular toxicity. We recommend restriction of ACR in food and use of Ferula sp. plants with caution especially in patients with impotence

Brominated flame retardants in children's room : concentration, composition, and health risk assessment

Children spend most of their daily time indoors. Many of the items used indoors, such as furniture, electronics, textile, and children toys, are treated with chemicals to provide longevity and fulfil the safety standards. However, many chemicals added to these products are released into the environment during leaching out from the treated products. Many studies have reported brominated flame retardants (BFRs) in indoor environments; however, few have focused on environments specified for young children. In this study, paired air (PM10) and dust samples were collected from the rooms (n = 30) of Saudi children. These samples were analyzed for different congeners of polybrominated diphenyl ethers (PBDEs) and three important alternative flame retardants using gas chromatography-mass spectrometry. Decabromodiphenyl ether (BDE 209) was the most important analyzed BFR in dust and PM10 samples with a median value of 3150 ng/g of dust and 75 pg/m3. This indicates the wider application of BDE 209 has implications for its occurrence, although its use has been regulated for specified uses since 2014. Among alternative BFRs, 2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), Bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), and 1,2-Bis(2,4,6-tribromophenoxy)ethane (BTBPE) were found with a median levels of 10, 15 and 8 ng/g of dust, respectively. However, alternative BFRs were present in 10 samples. The calculated long term and daily exposures via indoor dust and PM10 of Saudi children from their rooms were well below the respective reference dose (RfD) values. Nonetheless, the study highlights BDE 209 at higher levels than previously reported from household dust in Saudi Arabia. The study warrants further extensive research to estimate the different classes of chemical exposure to children from their rooms

Cadaver dissection: A positive experience among Saudi female medical students

Objectives: The objectives of this study were to evaluate first-year undergraduate female preclinical medical students' behaviours, experiences, and emotions regarding cadaver dissection. The evaluation was performed during the 2013–2014 academic year, six months after starting the dissection course. Methods: A 14-statement questionnaire was administered to a group of 200 first-year undergraduate female preclinical medical students at the College of Medicine, King Abdulaziz University (KAU), KSA. For each question, the students responded by selecting either “Yes,” “No,” or “Undecided.” Statistical analysis was performed after collection of the questionnaire responses. Results: The results showed that 90% of the students agreed that cadaver dissection provided the best and shortest way to study anatomy. Also, 89% were excited during their first visit to the dissection room, and 79% were satisfied that dissection of a cadaver was ethically acceptable. The majority of the students (over 90%) declared that dissection of a cadaver was one of the best teaching strategies for facilitating the acquisition of knowledge of human anatomy. Conclusions: Saudi female first-year undergraduate medical students at KAU showed positive attitudes toward cadaver dissection during their human anatomy course. This study prompts the need for exploration of gender differences in perception regarding cadaver dissection