Patients with thalassemia major requiring regular blood transfusions accumulate iron that is toxic to the heart, liver, and endocrine systems. The following prospective, randomized trial was carried out to determine the effectiveness, in children and young adults, of combined deferiprone (DFP) and deferoxamine (DFO) in reducing transfusional iron overload compared to either drug alone and to assess the safety and tolerability of DFP. Sixty-six patients were randomized into three treatment arms: daily DFP combined with DFO twice weekly; daily DFP only; and DFO only 5 days/week. Fifty-six patients completed the 54 weeks and were assessed by different indices. A significant reduction of liver iron concentration and serum ferritin was observed in all three arms while significant reduction of liver iron score was observed in patients on combination therapy only. Cardiac function did not significantly change in any arm. Compliance improved in patients who received combined therapy. Toxicity of DFP was mild to moderate and acceptable; most commonly, transient arthropathy and nausea/vomiting were observed. Thus, combination therapy has shown to be effective in reducing iron overload in thalassemia patients.

Most synthetic coloured additives are carcinogenic; teratogenic and cause allergic reactions. In this study, the effects of synthetic azo dyes (sunset yellow FCF and carmoisine), as well as their degraded products (sulphanilic acid and naphthionic acid), on both true and pseudo-cholinesterases (ChEs) are studied. The results indicate that the synthetic azo dyes and their degraded products inhibit both human true and pseudo-ChE activities in vitro. The concentration of coloured additive that cause 50% inhibition (IC50) and enzyme inhibitor dissociation constant (Ki) show that sunset yellow FCF produces greater inhibition of both true and pseudo-ChEs than does carmoisine and sulphanilic acid, while naphthionic acid produces greater inhibition of pseudo-ChE only. Ki indicates that the affinity of sulphanilic acid for both true and pseudo-ChEs is higher than the other three inhibitors. Inhibition of both true and pseudo-ChEs by sunset yellow FCF is of mixed (competitive and non-competitive) type, but carmoisine and sulphanilic acid are non-competitive. Naphthionic acid produces a competitive inhibition kinetic with plasma ChE only. This inhibition is abolished by dialysis, indicating that their effects are reversible. The effects of sunset yellow FCF, carmoisine, sulphanilic acid and naphthionic acid on rat true and pseudo-ChEs are investigated. The data clearly show that there is a significant decrease in enzyme activity. Sulphanilic acid and sunset yellow FCF are the most potent in vivo inhibitors of true ChE and pseudo-ChE, respectively.

Cadmium (Cd) has long been noted to induce neurodegenerative disorders. Therefore, this study aimed to assess the toxicological impact of Cd on rat brains and evaluate the possible ameliorative impact of omega-3 fatty acids as a protective agent of nervous system. Rats were divided into four groups: group I supplemented orally with saline; group II intoxicated with CdCl2 (5 mg/kg b.w. orally), and groups III and VI supplemented with omega-3 (100 mg/kg b.w. orally) simultaneously or before CdCl2 administration, respectively. Cd intoxication induced biochemical and histopathological disturbances in treated rats. Omega-3 fatty acid considerably improved the Cd-associated biochemical changes, reduced the elevation of lipid peroxidation, and normalized the Cd impact on the levels of superoxide dismutase, catalase, glutathione-S-transferases, 8-hydroxydeoxyguanosine, heatshock protein70, nuclear factor-κB, and interferon-γ as well as of neuronal enzymes such as acetylecholinesterase and monoamine oxidase within the brains of treated rats. Additionally, histological findings supported the results that Cd treatment-induced neurodegenerative changes and that polyunsaturated fatty acids act as antioxidants and neuroprotective agents against Cd toxicity. Co-treatment with omega-3 fatty acid was more beneficial than pretreatment. Thus, omega-3 fatty acid should be included in diet to prevent or suppress neurodegenerative disorders caused by continuous exposure to Cd.

The study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO 2 injection caused a significant decrease in Hb in rats, while serum levels of TNF-a, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO 2 injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.