Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model.

BACKGROUND: It is necessary to develop advanced therapies utilizing natural ingredients with anti-inflammatory qualities in order to lessen the negative effects of chemotherapeutics. RESULTS: The bioactive N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine hydrochloride (NIQBD) was synthesized. After that, soluble starch nanoparticles (StNPs) was used as a carrier for the synthesized NIQBD with different concentrations (50 mg, 100 mg, and 200 mg). The obtained StNPs loaded with different concentrations of NIQBD were coded as StNPs-1, StNPs-2, and StNPs-3. It was observed that, StNPs-1, StNPs-2, and StNPs-3 exhibited an average size of 246, 300, and 328 nm, respectively. Additionally, they also formed with homogeneity particles as depicted from polydispersity index values (PDI). The PDI values of StNPs-1, StNPs-2, and StNPs-3 are 0.298, 0.177, and 0.262, respectively. In vivo investigation of the potential properties of the different concentrations of StNPs loaded with NIQBD against MTX-induced inflammation in the lung and liver showed a statistically substantial increase in levels of reduced glutathione (GSH) accompanied by a significant decrease in levels of oxidants such as malondialdehyde (MDA), nitric oxide (NO), advanced oxidation protein product (AOPP), matrix metalloproteinase 9/Gelatinase B (MMP-9), and levels of inflammatory mediators including interleukin 1-beta (IL-1ß), nuclear factor kappa-B (NF-κB) in both lung and liver tissues, and a significant decrease in levels of plasma homocysteine (Hcy) compared to the MTX-induced inflammation group. The highly significant results were obtained by treatment with a concentration of 200 mg/mL. Histopathological examination supported these results, where treatment showed minimal inflammatory infiltration and congestion in lung tissue, a mildly congested central vein, and mild activation of Kupffer cells in liver tissues. CONCLUSION: Combining the treatment of MTX with natural antioxidant supplements may help reducing the associated oxidation and inflammation.

Bombax ceiba Linn. leaf extract rich in phenolic compounds to mitigate non-alcoholic fatty liver-related complications in experimental model.

OBJECTIVES: Obesity, diabetes mellitus, insulin resistance (IR), and hypertriglyceridemia are common features observed in non-alcoholic fatty liver diseases (NAFLD). There is a critical medical necessity to find novel therapeutics that can halt the development of NAFLD. METHODS: Bombax ceiba Linn. leaf extract was prepared and its phytochemical profile was determined. Standard and high carbohydrate high-fat diets (HCHF) were prepared. Rats were fed HCHF for 18 weeks to induce a non-alcoholic fatty liver (NAFL) model. Forty male rats were divided into control, B. ceiba Linn. leaf extract, NAFL, prophylactic, and treated groups. Serum fasting blood sugar (FBS), insulin, insulin resistance (HOMA-IR), cholesterol, high-density lipoprotein (HDL), triglycerides (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), intelectin-1 (ITLN1), p38 MAP kinase (MAPK), peroxisome proliferator-activated receptor alpha (PPAR-α), and interleukin-6 (IL-6) were evaluated. RESULTS: Data obtained showed that HCHF-induced NAFL resulting in a significant increase in FBS, serum insulin, HOMA-IR, cholesterol, LDL, TG, ALT, AST, and IL-6 and a significant decrease in serum levels of HDL, ITLN1, p38 MAP kinase, and PPAR-α compared to the control group. The analysis of B. ceiba Linn. leaf extract showed high content of phenol compounds which may cause a significant decrease in the levels of FBS, insulin, HOMA-IR values, lipid profile, and levels of IL-6 while a significant increase in serum levels of LDL, ITLN1, p38 MAP kinase, and PPAR-α compared to the NAFL group. CONCLUSIONS: B. ceiba Linn. Leaf extract is a highly protective and promising therapeutic agent against inflammation and oxidative stress in the NAFLD model induced by HCHF.

Preparation of pumpkin oil-based nanoemulsion as a potential estrogen replacement therapy to alleviate neural-immune interactions in an experimental postmenopausal model.

As estrogen production decreases during menopause; the brain's metabolism tends to stall and become less effective. Estrogen most likely protects against neurodegeneration. Consequently, a comprehensive study of the benefits of hormone replacement therapy as a neuroprotective effect is urgently required. This study was designed to fabricate pumpkin seed oil nanoparticles (PSO) in nanoemulsion form (PSO-NE) and investigate their potential role in attenuating the neural-immune interactions in an experimental postmenopausal model.Sixty female white albino rats were divided into six groups: control, sham, ovariectomized (OVX), and three OVX groups treated with 17ß-estradiol, PSO, and PSO-NE respectively. Transmission Electron Microscopy (TEM), and particle size analyzer were performed for nanoemulsion evaluation. Serum levels of estrogen, brain amyloid precursor protein (APP), serum levels of nuclear factor kappa B (NF-κß), interleukin 6 (IL-6), transthyretin (TTR), and synaptophysin (SYP) were evaluated. The expression of estrogen receptors (ER-α, ß) in the brain tissue was estimated. The findings revealed that the approached PSO-NE system was able to reduce the interfacial tension, enhance the dispersion entropy, lower the system free energy to an extremely small value, and augment the interfacial area. PSO-NE, showed a significant increase in the levels of estrogen, brain APP, SYP, and TTR accompanied with a significant increased in the expression of brain ER-α, ß compared to the OVX group. In conclusion, the phytoestrogen content of PSO exhibited a significant prophylactic effect on neuro-inflammatory interactions, ameliorating both estrogen levels and the inflammatory cascades.

Dynamic expression of H19 and MALAT1 and their correlation with tumor progression biomarkers in a multistage hepatocarcinogenesis model.

Hepatocellular carcinoma (HCC) progresses sequentially in a stepwise pattern. Long noncoding RNA (lncRNA) can regulate the complex cascade of hepatocarcinogenesis. Our study aimed to elucidate the expression profile of H19 and MALAT1 during the different stages of hepatocarcinogenesis and the correlation between H19 and MALAT1 with the genes implicated in the carcinogenesis cascade. We employed a chemically induced hepatocarcinogenesis murine model to mimic the successive stages of human HCC development. Using real-time PCR, we analyzed the expression patterns of H19 and MALAT1, as well as the expression of biomarkers implicated in the Epithelial-Mesenchymal transition (EMT). The protein expression of the mesenchymal marker vimentin was also evaluated using immunohistochemistry in the stepwise induced stages. The histopathological evaluation of the liver tissue sections revealed significant changes during the experiment, with HCC developing at the final stage. Throughout the stages, there was a dynamic significant increase in the expression of H19 and MALAT1 compared to the normal control. Nevertheless, there was no significant difference between each stage and the preceding one. The tumor progression biomarkers (Matrix Metalloproteinases, vimentin, and ß-catenin) exhibited the same trend of steadily increasing levels. However, in the case of Zinc finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2), the significant elevation was only detected at the last stage of induction. The correlation between lncRNAs and the tumor progression biomarkers revealed a strong positive correlation between the expression pattern of H19 and MALAT1 with Matrix Metalloproteinases 2 and 9 and vimentin. Our findings imply that genetic and epigenetic alterations influence HCC development in a stepwise progressive pattern.

Eicosapentaenoic acid loaded silica nanoemulsion attenuates hepatic inflammation through the enhancement of cell membrane components.

BACKGROUND: Liver inflammation is a multistep process that is linked with cell membrane fatty acids composition. The effectiveness of eicosapentaenoic acid (EPA) undergoes an irreversible change during processing due to their unsaturated nature; so the formation of nanocarrier for EPA is crucial for improving EPA's bioavailability and pharmacological properties. OBJECTIVE: In this study we aimed to evaluate the efficiency of EPA alone or loaded silica nanoemulsion on the management of hepatic inflammation induced by diethyl nitrosamine (DEN) through the enhancement of the cell membrane structure and functions. METHODS: The new formula of EPA was prepared to modify the properties of EPA. Forty-eight male Wistar albino rats were classified into: control, EPA, EPA loaded silica nanoemulsion (EPA-NE), DEN induced hepatic inflammation; DEN induced hepatic inflammation treated with EPA or EPA -NE groups. Plasma tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), liver hydroxyproline (Hyp) content, and liver oxidant and anti-oxidants were estimated. Urinary 8- hydroxyguanozine (8- OHdG) and erythrocyte membrane fatty acids fractions were estimated by High-performance liquid chromatography (HPLC). Also, histopathology studies were done to verify our hypothesis. RESULTS: It was appeared that administration of EPA, in particular EPA loaded silica nanoemulsion, ameliorated the inflammatory response, increased the activity of the anti-oxidants, reduced levels of oxidants, and improved cell membrane structure compared to hepatic inflammation induced by DEN group. Histopathological examination confirmed these results. CONCLUSION: EPA and notably EPA loaded silica nanoemulsion strongly recommended as a promising supplement in the management of hepatic inflammation.

Synthesis and characterization of berberine-loaded chitosan nanoparticles for the protection of urethane-induced lung cancer.

Lung cancer is one of the most common types of malignant tumors of the respiratory system and has the highest rates of incidence and mortality of malignant tumors. This study aimed to synthesize and characterize berberine-loaded chitosan nanoparticles (BBR-COSNPs) and to evaluate their protective effects against urethane-induced lung cancer. Forty male albino mice were divided into four groups, with the first serving as a negative control and the other three groups were injected intraperitoneally with urethane (1 mg/kg b.w) each other day for 1 week then group 2 was served as a positive control, however, groups 3 and 4 were treated orally with a daily dose of BBR or BBR-COSNPs (75 mg/kg b.w) for 10 consecutive weeks. Blood and lung tissue samples are collected for laboratory assay. The BBR-COSNPs were spherical, with an average particle size of 45.56 nm and zeta potential of 39.82 1.82 mV. The in vivo data demonstrated that mice given urethane alone had a significant increase in MDA, NO, NF-κB level, HIF1-α, and COX-2-positive expression in the lung tissue and serum VEGFR2, ALT, AST, urea, and creatinine accompanied with a significant decrease in GSH, SOD, caspase 9 in the lung tissue and serum BAX. Co-treatment with BBR-COSNPs suppressed lung cancer growth and promoted apoptosis by modulating serum BAX and lung caspase 9 gene expressions. In addition, BBR-COSNPs inhibited tumor angiogenesis by reduction in levels of serum VEGFR2 and lung HIF 1 gene expression. It is possible to conclude that BBR-COSNPs can be used in oral administration formulations for lunganticancer therapy.

Formulation of wheat germ oil based on nanoemulsions to mitigate cisplatin's nephrotoxic effects.

The present study was designed to fabricate wheat germ oil nanoemulsions (WGO-NEs) by using two different emulsifiers in their physical properties and their chemical structures which were Triton X-100 and Lecithin to form Triton X-100 coated WGO nanoemulsion (WGOT-NE) and Lecithin coated WGO nanoemulsion (WGOL-NE) then characterized them using Transmission Electron Microscopy, Scanning Electron Microscopy (SEM) and Dynamic light scattering (DLS) and study their biological effects against cisplatin-induced nephrotoxicity. The experimental study was performed on fifty male albino rats divided into 5 groups. healthy group, group injected with a single dose of cisplatin (CP), group injected with a single dose of CP then received WGO orally, group injected with a single dose of CP then received WGOL-NE and group injected a single dose of CP then received WGOT-NE. The results showed that the shape of the particles of WGOL-NE is spherical with poorly aggregation and average particle size is 161.2 nm while WGOT-NE is nearly spherical but with noticeable agglomeration and an average particle size of 194.6 nm. In the experimental study, the results showed involvement of cisplatin in nephrotoxicity through disturbance kidney function and histological examination of the cortical tissue of the kidney and increased biochemical markers related to inflammation, oxidative stress, and apoptotic pathway. Otherwise, treatment with WGO, WGOT-NE, and WGOL-NE increased a significant amelioration in all the biochemical markers. In conclusion, WGOT-NE and WGOL-NE were more efficient than the native WGO in attenuating the kidney damage induced by CP although WGOL-NE showed the nearest results to the control group.

Chitosan and solid lipid nanoparticles enhance the efficiency of alpha-lipoic acid against experimental neurotoxicity.

Alpha-lipoic acid (α-LA) is characterized by its unpleasant odor, poor bioavailability and stability. Nanotechnology was applied to overcome this limitation. So we aimed in this study to formulate α-LA in two different forms of chitosan nanoparticles (CsNPs) and solid lipid nanoparticles (SLNPs) and characterize them in terms of physical properties and biological activities against aluminum chloride (AlCl3)-induced neurotoxicity in rats. The vivo study was processed on 50 rats divided into 5 groups as follow: control, neurotoxic, treated α-LA, treated α-lipoic acid-loaded chitosan nanoparticles (α-LA-CsNPs) and treated α-lipoic acid-loaded solid lipid nanoparticles (α-LA-SLNPs) groups. The result was depicted by transmission electron microscopy (TEM) revealed that α-LA-SLNPs had a regular spherical shape while α-LA-CsNPs showed an irregular spherical form. Dynamic light scattering (DLS) analysis showed that the average particle size for α-LA-SLNPs was about 71 nm and for α-LA-CsNPs was about 126 nm. After the experimental period, we observed that AlCl3 administration significantly increased oxidative stress, neuroinflammation and apoptosis and decreased brain fatty acid contentsand brain-derived neurotrophic factor,while α-LA, α-LA-CsNPs and α-LA-SLNPs were able to ameliorate these negative changes in the neurotoxic rats. However, the effect of the α-LA-loaded NPs was more prominent than that of pristine α-LA but the α-LA-SLNPs group was almost close to the control group. Conclusion: α-LA can attenuate neurotoxicity induced by AlCl3, attributed to its anti-inflammatory, antioxidant and anti-apoptotic activities in addition to the effectiveness of the encapsulation technique that can increase the efficiency and stability of α-LA. Moreover, α-LA-SLNPs are more efficient than α-LA-CsNPs.

Prophylactic effect of probiotics fortified with Aloe vera pulp nanoemulsion against ethanol-induced gastric ulcer.

The purpose of this study was designed to evaluate the protective effect of probiotics fortified with Aloe vera pulp nanoemulsion on ethanol-induced gastric ulcer (GU). Freshly harvested Aloe vera pulp nanoemulsion was prepared and subsequently inoculated with 2% of the activated yogurt starter culture of Streptococcus thermophilus and Lactobacillus delbreukii subsp. bulgaricus (1:1). Chemical composition and physicochemical characterization of yogurt and the Aloe vera pulp nanoemulsion were assessed. GU was induced by ethanol. Rats were randomly assigned into control, GU, and four prophylactic groups including probiotics fortified with Aloe vera pulp nanoemulsion in the percentage of 0%, 10%, 20%, and 30% respectively. Serum levels of paraoxynase (POX) and tissue levels of malondialdehyde (MDA), nitric oxide (NO), and catalase (CAT) activity were assessed. Serum levels of nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1ß), matrix metalloproteinase-9 (MMP-9), ceramide, and homocysteine (Hcy) were evaluated. Results indicated that the Aloe vera pulp nanoemulsion was appeared in spherical nano form with droplets diameter around 330 nm. Ethanol induces GU to cause a significant increase in the levels of MDA, NO, NF-κB, IL-1ß, MMP-9, Hcy, and ceramide along with a significant decrease in POX and CAT activities compared to the control group (p < 0.05). Pretreatment with different concentrations of probiotics fortified with Aloe vera pulp nanoemulsion with, especially the 30% concentration, significantly reduce the oxidative stress and ameliorate the release of different inflammatory mediators suggesting it as a promising approach in the protection against GU via scavenging superoxide radicals and inhibiting the activation of the inflammatory signaling cascades.

Influence of irisin on diet-induced metabolic syndrome in experimental rat model.

OBJECTIVE: To evaluate the influence of irisin on the experimental paradigm of non-alcoholic fatty liver (NAFL) as a part of MetS cluster. METHODS: Forty male albino rats were divided into four groups; normal control, standard diet + irisin, high carbohydrate and fat diet (HCHF), and HCHF + irisin. After the experimental period, levels of fasting blood sugar (FBS), insulin, lipid profile, kidney functions, salusin-alpha (Sal-α), adropin, and retinol-binding protein-4 (RBP-4) were evaluated. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) expression in skeletal muscle was evaluated by quantitative real-time PCR. Aorta, liver, pancreas, and skeletal muscle tissue samples were prepared for histopathological examination. RESULTS: Rats administrated HCHF showed elevated levels of FBS, lipid profile, kidney functions, RBP-4, and downregulation of PGC-1α expression along with a decline in levels of insulin, Sal-α, and adropin while administration of irisin significantly attenuated these levels. CONCLUSIONS: Irisin as based therapy could emerge as a new line of treatment against MetS and its related diseases.

Oxidative Stress in Autism Spectrum Disorder.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis-induced colorectal cancer.

Early detection of colorectal cancer and monitoring the progress in colon carcinogenesis stages is essential to reduce mortality. Therefore, there is continuous search for noninvasive biomarkers with high stability and good sensitivity and specificity. miRNAs have attracted attention as promising biomarkers as they are stably expressed in circulation. The aim of our study is to evaluate the aberrant expression of circulating miRNAs during the stepwise progress of colitis-associated colon cancer. This was accomplished through assessing the expression levels of five miRNAs (miR-141, miR-15b, miR-17-3p, miR-21, and miR-29a) in serum and their corresponding tissue samples through the different cycles of colorectal carcinogenesis cascade using the azoxymethane/dextran sulfate sodium murine model. We also compared the diagnostic performance of these selected miRNAs with the conventional tumor biomarkers CEA and CA 19-9. The results of our study revealed that the expression levels of those miRNAs were dynamically changing in accordance with the tumor development state. Moreover, their aberrant expression in serum was statistically correlated with that in tissue. Our data also revealed that serum miR-15b, miR-21, and miR-29a showed the best performance in terms of diagnostic power. Our findings highlight the efficiency of these circulating miRNAs not only for early diagnostics purposes, but also for monitoring progress in the colorectal carcinogenesis process, and therefore encouraging integrating these noninvasive biomarkers into the clinical diagnostic settings beside the traditional diagnostic markers for accurate screening of the early progress of colon carcinogenesis.

Curcumin-loaded PLA-PEG copolymer nanoparticles for treatment of liver inflammation in streptozotocin-induced diabetic rats.

This report focused on loading curcumin (CUR) drug into biodegradable Polylactide-poly(ethylene glycol) (PLA-PEG) copolymer nanoparticles as an effective anti-inflammatory agent in vivo to overcome the limitations resulted from the free CUR. By a simple nano-emulsification technique, hydrophobic CUR was loaded into hydrophobic polymer's segments and stabilized by cationic surfactant. They were then characterized by DLS, TEM, and SEM techniques providing monodispersed and spherical nanoparticles with an average diameter of 117 nm and high surface charge of +35 mV. Thereafter, they were orally administrated into five groups of rats, typically, control (healthy rats), streptozotocin (STZ)-induced diabetic rats, diabetics treated with free CUR, diabetics treated with PLA-PEG NPs, and diabetics treated with CUR-encapsulated PLA-PEG NPs. Next, complete blood analyses were assessed including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and nuclear factor kappa B (NF-Ò¡B), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), cyclooxygenase (COX-2), Peroxisome proliferator-activated receptors (PPAR-γ) and transforming growth factor-ß1 (TGF-ß1). The obtained results demonstrated that diabetes initially produced liver inflammation in rats manifested by leveraging the mean levels of serum AST, ALT inducing oxidative stress resulting in a clear increase in the levels of hepatic MDA and NO concomitant with a remarkable decrease in GSH. Moreover, diabetes significantly increased serum NF-Ò¡B, hepatic COX-2 and TGF-ß1, while highly reduced hepatic PPAR-γ. In contrast, both CUR free and CUR-encapsulated NPs ameliorated the negative changes in diabetes but CUR-encapsulated NPs showed more pronounced treated effect than free CUR. In addition, histopathological investigations were performed on the liver tissues of all groups, showing a mitigation in inflammation while treating with CUR-NPs.

Altered S100 Calcium-Binding Protein B and Matrix Metallopeptidase 9 as Biomarkers of Mesial Temporal Lobe Epilepsy with Hippocampus Sclerosis.

Mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) is the most common form of partial epilepsy. The aim of the present study is to highlight possible and suitable biomarkers that can help in the diagnosis and prognosis of this intractable form of epilepsy. The study was carried out on 30 epileptic patients of both sexes with complex partial seizures, having an age ranging from 4 to 30 years and were selected from the outpatient epilepsy clinic at the Kasr El-Aini Hospital in Cairo, Egypt. Thirty healthy children and young adults, age- and sex-matched to the patients, were included in the study as controls. Patients with epilepsy and healthy controls were subjected to a set of laboratory analyses including S100 calcium-binding protein B (S100B), matrix metallopeptidase 9 (MMP9), C-reactive protein (CRP), and prolactin (PRL), in addition to neurophysiological, radiological, and psychometric assessments, on the basis of the recent evidence of the field. The results of this study showed a marked increase in the investigated biomarkers in patients with epilepsy compared to controls. The performance of the epileptic patients in psychometric assessments was below the average threshold, with the MRI analysis showing specific findings of mesial temporal sclerosis (MTS) and EEG showing anterior temporal spikes. A significant negative correlation was found between MMP9 and psychometric test. On the other hand, a significant positive correlation was observed between seizure severity and the indicated biomarker. The present study suggests that S100B and MMP9 could be used as biomarkers for neuronal injury and helps in the prognosis of MTLE.

Diagnostic and Severity-Tracking Biomarkers for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder afflicting about one in every 68 children. It is behaviorally diagnosed based on a triad of symptoms, including impairment in communication, impairment in sociability and abnormal and stereotypic behavior. The subjectivity of behavioral diagnosis urges the need for clinical biomarker tests to improve and complement ASD diagnosis and treatment. Over the past two decades, researchers garnered a broad range of biomarkers associated with ASD and often correlating with the severity of ASD, which includes metabolic and genetic biomarkers or neuroimaging abnormalities. Metabolic biomarkers are either involved in key pathways such as a trans-sulfuration pathway or produced due to the derangement of these pathways in the case of oxidative stress. Recent studies reported several genetic abnormalities related to ASD, encompassing various mechanisms, from copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) to chromosomal anomalies. However, it is still premature to consider these genetic variants as true biomarkers for ASD, due to their low reproducibility and regional-specific nature. Herein, we comprehensively review state of the art about major biomarkers reported in ASD and the association of some biomarkers with ASD symptoms and severity. It is important to establish those biomarkers to be able to help in the diagnosis and to optimize the treatment of ASD.

Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD.