Analysis of Melatonin-Modulating Effects Against Tartrazine-Induced Neurotoxicity in Male Rats: Biochemical, Pathological and Immunohistochemical Markers.

Tartrazine (E-102) is one of the most widely used artificial food azo-colors that can be metabolized to highly sensitizing aromatic amines such as sulphanilic acid. These metabolites are oxidized to N-hydroxy derivatives that cause neurotoxicity. Melatonin is a neurohormone. That possesses a free-radical scavenging effect. The present work was mainly designed to evaluate the possible ameliorative role of melatonin against tartrazine induced neurotoxicity in cerebral cortex and cerebellum of male rats. Adult male rats were administered orally with tartrazine (7.5 mg/kg) with or without melatonin (10 mg/kg) daily for four weeks. The data revealed that tartrazine induced redox disruptions as measured by significant (p < 0.05) increased malondialdehyde (MDA) level and inhibition of (GSH) concentration and catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzyme activities. Besides, brain acetyl cholin (Ach) and gamma-aminobutyric acid (GABA) were elevated while, dopamine (DA) was depleted in trtrazine -treated rats. Moreover, tartrazine caused a significant (p < 0.05) increase in the brain interleukin-6 (IL-6), interleukin-1ß (IL-1 ß) and tumor necrosis factor-α (TNFα). At the tissue level, tartrazine caused severe histopathological changes in the cerebellum and cerebral cortex of rats. The immunohistochemical results elucidated strong positive expression for Caspase-3 and GFAP and weak immune reaction for BcL2 and synaptophysin in tatrazine- treated rats. The administration of melatonin to tartrazine -administered rats remarkably alleviated all the aforementioned tartrzine-induced effects. It could be concluded that, melatonin has a potent ameliorative effect against tartrazine induced neurotoxicity via the attenuation of oxidative/antioxidative responses.

P2X4 signalling contributes to hyperactivity but not pain sensitization comorbidity in a mouse model of attention deficit/hyperactivity disorder.

Introduction: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by hyperactivity, inattention, and impulsivity that often persist until adulthood. Frequent comorbid disorders accompany ADHD and two thirds of children diagnosed with ADHD also suffer from behavioural disorders and from alteration of sensory processing. We recently characterized the comorbidity between ADHD-like symptoms and pain sensitisation in a pharmacological mouse model of ADHD, and we demonstrated the implication of the anterior cingulate cortex and posterior insula. However, few studies have explored the causal mechanisms underlying the interactions between ADHD and pain. The implication of inflammatory mechanisms has been suggested but the signalling pathways involved have not been explored. Methods: We investigated the roles of purinergic signalling, at the crossroad of pain and neuroinflammatory pathways, by using a transgenic mouse line that carries a total deletion of the P2X4 receptor. Results: We demonstrated that P2X4 deletion prevents hyperactivity in the mouse model of ADHD. In contrast, the absence of P2X4 lowered thermal pain thresholds in sham conditions and did not affect pain sensitization in ADHD-like conditions. We further analysed microglia reactivity and the expression of inflammatory markers in wild type and P2X4KO mice. Our results revealed that P2X4 deletion limits microglia reactivity but at the same time exerts proinflammatory effects in the anterior cingulate cortex and posterior insula. Conclusion: This dual role of P2X4 could be responsible for the differential effects noted on ADHD-like symptoms and pain sensitization and calls for further studies to investigate the therapeutic benefit of targeting the P2X4 receptor in ADHD patients.

Biochemical and histological alterations induced by nickel oxide nanoparticles in the ground beetle Blaps polychresta (Forskl, 1775) (Coleoptera: Tenebrionidae).

The present study evaluates the effect of nickel oxide nanoparticles on some biochemical parameters and midgut tissues in the ground beetle Blaps polychresta as an indicator organism for nanotoxicity. Serial doses of the NiO-NPs colloid (0.01, 0.02, 0.03, 0.04, 0.05, and 0.06 mg/g) were prepared for injecting into the adult beetles. Insect survival was reported daily for 30 days, and the sublethal dose of 0.02 mg/g NiO-NPs was selected for the tested parameters. After the treatment, nickel was detected in the midgut tissues by X-ray microanalysis. The treated group demonstrated a significant increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities when compared to the untreated group. However, the treated group demonstrated a significant decrease in ascorbate peroxidase (APOX) activity when compared to the untreated group. Histological and ultrastructural changes in the midgut tissues of treated and untreated beetles were also observed. The current findings provide a precedent for describing the physiological and histological changes caused by NiO-NPs in the ground beetle B. polychresta.

Nickel oxide nanoparticles induce genotoxicity and cellular alterations in the ground beetle Blaps polycresta (Coleoptera: Tenebrionidae).

Nickel nanoparticles (Ni-NPs) have advantageous applications in the industry; however, little is known of their adverse effects on biological tissues. In the present study, the ground beetle Blaps polycresta was employed as a sensitive indicator for nickel oxide nanoparticles (NiO-NPs) toxicity. Adult male beetles were injected with six dose levels of NiO-NPs (0.01, 0.02, 0.03, 0.04, 0.05, and 0.06 mg/g body weight). Mortality was reported daily over 30 days under laboratory conditions to establish an LD50. Nickel was detected in the testicular tissues of the beetles using X-ray analysis and transmission electronic microscopy. Beetles treated with the sublethal dose of 0.02 mg/g were selected to observe molecular, cellular, and subcellular changes. Gene transcripts of HSP70, HSP90, and MT1 were found to be increased >2.5-, 1.5-, and 2-fold, respectively, in the treated group compared with the controls. Decreased gene expression of AcPC01, AcPC02, and AcPC04 (≤1.5-, ≤2-, and < 2.5-fold, respectively, vs. controls) also were reported in the treated group. Under light microscopy, various structural changes were observed in the testicular tissues of the treated beetles. Ultrastructure observations using scanning and transmission electron microscopy showed severe damage to the subcellular organelles as well as deformities of the heads and flagella of the spermatozoa. Therefore, the present study postulated the impact of NiO-NPs in an ecological model.

Protective effects of quercetin supplementation against short-term toxicity of cadmium-induced hematological impairment, hypothyroidism, and testicular disturbances in albino rats.

The aim of this study was to evaluate the probable protective effect of quercetin (QUE) against cadmium (Cd)-induced sub-chronic toxicity in rats. Adult male rats were given either Cd (as cadmium chloride; 5 mg/kg) alone or in combination with QUE (50 mg/kg) daily for 4 weeks by oral gavage. At the end of the experimental period, Cd accumulation, and selected hematological, thyroid, and reproductive markers were assessed. Results revealed that Cd treatment significantly increased Cd concentrations in blood, thyroid gland, and testicular tissue of rats. Cd also caused a decline in hemoglobin content, hematocrit value, and total erythrocyte and leucocyte counts. Further, significant suppressions in the blood levels of hormones related to thyroid gland function, and male reproductive hormones (i.e., testosterone, luteinizing hormone and follicle-stimulating hormone), were observed in Cd-treated rats compared to the control. In parallel, low sperm count and sperm motility, increased sperm abnormalities, and marked pathology occurred in testis. Combination with QUE recorded amelioration of the deleterious effects of Cd, involving regulation of hematological toxicity and thyroid hormonal levels and subsequently modulation of testicular function. In conclusion, it appears that dietary QUE can rescue from Cd-induced hematological dysfunctions and testicular damage by reversing the hypothyroid state.

Ameliorative potentials of quercetin against lead-induced hematological and testicular alterations in Albino rats.

Lead is one of the oldest environmental and occupational toxins. Health hazards from increased lead exposure as a result of industrial and environmental pollution are recognized. The aim of the present study was to investigate the protective effects of quercetin as a model of an antioxidant drug against the toxic effects of lead acetate on the blood and the testis of rats. The lead concentrations were determined in blood and the testis. Testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were assessed in serum. Hemoglobin (Hb) content, packed cell volume (PCV), white blood cell (WBC) and red blood cell (RBC) counts were evaluated in the whole blood. Our results showed that administration of lead acetate was associated with an increased lead levels in blood as well as in the testis. Lead acetate administration also caused a decrease in testicular function, Hb content, PCV and RBC count in comparison to the respective mean values of the control. In addition, lead acetate increased WBC count and induced alterations in sperm count, sperm motility and sperm abnormality and histopathology. In the contrary, administration of lead acetate along with quercetin partially restored the studied parameters to normal values. In conclusion, the treatment with quercetin may provide a partial protection against the toxic effects induced by lead acetate in blood and the testis of rats.

Curcumin Ameliorates Lead (Pb(2+))-Induced Hemato-Biochemical Alterations and Renal Oxidative Damage in a Rat Model.

This study aims to evaluate the protective role of curcumin (Curc) against hematological and biochemical changes, as well as renal pathologies induced by lead acetate [Pb (CH3COO)2·3H2O] treatment. Male albino rats were intraperitoneally treated with Pb(2+) (25 mg of lead acetate/kg b.w., once a day) alone or in combination with Curc (30 mg of Curc/kg b.w., twice a day) for 7 days. Exposure of rats to Pb(2+) caused significant decreases in hemoglobin (Hb) content, hematocrit (Ht) value, and platelet (Plt) count, while Pb(2+)-related leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia, and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum of Pb(2+) group compared to that of control. Furthermore, significantly high levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density lipoprotein (HDL-C) level were also seen in blood after injection of Pb(2+). Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb(2+) produced marked histo-cytological alterations in the renal cortex. Co-administration of Curc to the Pb(2+)-treated animals restored most of the parameters mentioned above to near-normal levels/features. In conclusion, Curc appeared to be a promising agent for protection against Pb(2+)-induced toxicity.