ABSTRACT
Iron toxicity is a common toxicologic emergencies in young children. Repeated blood transfusions as in thalassemia results in chronic iron overload with cellular and tissue damage. Recent reports stated that iron induced heart failure and arrhythmia is the first cause of death in thalassemic patients. Iron chelation by deferoxamine is the classic treatment since 40 years. Recently deferiprone is described as the first oral chelating agent to be used in iron loaded patients. The aim of the study is to evaluate the chelating effects of deferoxamine and deferiprone clinically in thalassemic - children and experimentally in albino rats by histopathological and ultrastructural examination of the liver and the heart. Forty transfusion dependent B-thalassemic patients are classified into 2 groups Group I; received daily single S.C. injection of deferoxamine [40 mg /kg for 5 days] and Group II received daily single oral dose of deferiprone [50 mg/kg, as 3 divided doses at 8 hours interval for 7 days]. All patients are investigated by measuring serum ferritin level and MRI. One hundred adult albino rats are divided into 5 groups, Group [1]: negative control, Group [2]: Positive control, Group [3]; received daily I.P. dose of iron dextran [1125 mg/kg for 6 weeks] to induce iron overload, Group [4]; Iron overloaded rats, received daily I.P. dose of deferoxamine [100 mg/kg for 2 weeks], Group [5]; Iron overloaded rats, received daily oral dose of deferiprone [150 mg/kg for 2 weeks]. After the period of each group the rats were sacrificed, the liver and the heart were submitted to histopathological and ultrastructural examination. It is found that deferoxamine induced non significant decrease in the mean values of serum ferritin level and elevated iron concentration in detected by MRI, with iron deposits, focal necrosis, interrupted cardiac muscle fibers and wide intercellular space. Deferiprone treated group showed significant decrease in the mean value of serum ferritin levels, iron incorporation, and focal iron deposits, normal hepatic architecture, normal intercellular space and striated myofibrils with mild cellular infiltrates and normal mitochondria. On comparison of both drugs, deferiprone induced significant chelating effects than deferoxamine with lower incidence of side effects. It is concluded that deferiprone is an effective iron chelating agent in cases of chronic iron overload, capable of reversing iron overload induced hepatotoxic and cardiotoxic effects, with lower incidence of side effects than deferoxamine
ABSTRACT
Heroin addiction markedly affects the nutritional and metabolic status and frequently lead to malnutrition. The aim of our study is to compare the serum leptin concentration in 20 patients with heroin addiction before and after 6 months of detoxification and naltrexone maintenance treatment program with the group of age, sex and body mass index-matched healthy subjects. Basal serum leptin in heroin addicts was significantly decreased [3.2 +/- 0.4 versus 4.3+/-0.5ng/ml; P<0.05]. Moreover, positive correlation of serum leptin levels with body mass index was lost in heroin addicts compared to control group. Six months of naltrexone maintenance treatment program, serum leptin level was normalized. In conclusion serum leptin levels are markedly decreased in heroin addict patients and normalized in naltrexone maintenance treated patients
ABSTRACT
Methanol toxicity produces toxic injuries to the retina and optic nerve results in blindness. Formic acid [the toxic metabolite responsible for these toxic effects] is a mitochondrial toxin that increases the production of Reactive Oxygen Species resulting in oxidative stress cell injury. In the retina, glutathione acts as a vital defense mechanism against oxidative stress. N-acetylcysteine [NAC] is a glutathione precursor and acts as a free radical scavenger. In this study the role of NAC against methanol-induced retinal toxicity was evaluated in adult male albino rats. Group [I] [control: received normal saline], group [IIa]: [received daily oral toxic dose of methanol 3gmlkg for 72 hrs], group [IIb] [follow up group]: [received daily oral toxic dose of methanol 3gmlkg for 72 hrs then saved for follow up for 24 hrs], group [IIc]: [received daily oral toxic dose of methanol 3gm/kg for 72 hrs and single oral therapeutic dose of NAC 800mg/kg 24 hrs after the last dose of methanol], group [III]: [received single oral therapeutic dose of NAC 800mg/kg]. After the period of each group, the rats were sacrificed and were investigated by assessment of glutathione, glutathione peroxidase activity, histopathological and ultrastructural examination of retinal tissue. Methanol-toxicity induced a significant decrease in glutathione and glutathione peroxidase activity, with retinal edema and vaculation of photoreceptors inner segment and enlarged irregularly stained nuclei, and profound mitochondrial swelling with severely disrupted cristae, as compared with control. Follow up group showed a significant decrease in glutathione and glutathione peroxidase, as compared with control, and a significant increase in its activity as compared with methanol-toxicity, with mild alterations in photoreceptor mitochondria. NAC-treated group revealed a significant increase in glutathione and glutathione peroxidase, as compared with methanol toxicity, and a non significant difference in comparison with control and NAC groups, with normal retinal structures. It is concluded that methanol induced severe retinal toxicity that could be reversed by N-acetylcysteine administration through its action as a glutathione precursor and a free radical scavenger