Patients with iron overload frequently suffer from hemochromatosis of major organs, such as the heart and liver. Heart affection is the most common cause of death in patients with iron overload. Although the beneficial effects of deferoxamine (DFO) on iron-associated mortality are well documented, the role of deferiprone in the management of transfusional iron overload is controversial. The aim of this study was to compare the protective effect of iron chelators (DFO and deferiprone) individually and in combination with the anti-oxidant (vitamin C) in the prevention of myocardial damage. Sixty albino rats were divided into six groups: two control groups (noniron-loaded and iron-loaded) and four iron-loaded groups classified as follows: DFO group, DFO combined with vitamin C group, deferiprone group and deferiprone combined with vitamin C group. Heart tissue and blood samples were taken for histopathological examination of the heart, determination of total iron-binding capacity, 8-OH-deoxyguanosine (8-OH-dG), myocardial lipid peroxidation and glutathione (GSH) content. Less histopathological cardiac changes and a significant decrease in all biochemical parameters, except myocardial GSH, were observed in the deferiprone group. The addition of vitamin C improves the biochemical and histopathological changes in comparison to those rats administered DFO or deferiprone individually.

Background: Gold nanoparticles [GNPs] are significant scientific achievements which are effectively employed in medicine. However, in vivo biological impact of these particles should be assessed to investigate their safety on human health. Aim: Study of the biological effect of different gold nanoparticles doses on the liver of adult female rats exploring the novel mechanisms of gold nanoparticles induced liver damage. Materials and Methods: Forty adult female rats were separated into one control group [Group I] and two GNPs-treated groups [Group II; 40μg/kg and Group III; 400μg/kg]. Specimens of the liver were taken to be processed for the light and electron microscopy in addition to immunohistochemical staining technique for the p53 protein, tumor necrosis factor alpha [TNF-α] and B-cell lymphoma 2 [Bcl-2]. Results: Administration of gold nanoparticles to adult female rats caused various histological deterioration in the liver depending on the dose. Hepatocytes showed vacuolated cytoplasm and pyknotic nuclei. Dilation and congestion of the central veins, blood sinusoids, hepatic artery and portal vein were seen. Disrupted endothelial layer was observed in some central veins. An apparent increase in kupffer cells and mononuclear cellular infiltration were observed. The immunohistochemical results demonstrated a significant increase in p53 and TNF-α and decrease in Bcl-2 immunoreactions. Ultrastructurally, swollen or damaged mitochondria, dilated rough endoplasmic reticulum [RER] and apparent glycogen depletion were observed in the hepatocytes. Conclusion: Gold nanoparticles induced various dose dependent histological deterioration, inflammation and apoptosis in the liver of adult female rats. So, it should be given cautiously to females to avoid liver damage.

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Myonecrosis is a frequent clinical manifestation of envenomings by Viperidae snakes, mainly caused by the toxic actions of secreted phospholipase A2 (sPLA2) enzymes and sPLA2-like homologs on skeletal muscle fibers. A hallmark of the necrotic process induced by these myotoxins is the rapid appearance of hypercontracted muscle fibers, attributed to the massive influx of Ca2+ resulting from cell membrane damage. However, the possibility of myotoxins having, in addition, a direct effect on the contractile machinery of skeletal muscle fibers when internalized has not been investigated. This question is here addressed by using an ex vivo model of single-skinned muscle fibers, which lack membranes but retain an intact contractile apparatus. Rabbit psoas skinned fibers were exposed to two types of myotoxins of Bothrops asper venom: Mt-I, a catalytically active Asp49 sPLA2 enzyme, and Mt-II, a Lys49 sPLA2-like protein devoid of phospholipolytic activity. Neither of these myotoxins affected the main parameters of force development in striated muscle sarcomeres of the skinned fibers. Moreover, no microscopical alterations were evidenced after their exposure to Mt-I or Mt-II. In contrast to the lack of effects on skinned muscle fibers, both myotoxins induced a strong hypercontraction in myotubes differentiated from murine C2C12 myoblasts, with drastic morphological alterations that reproduce those described in myonecrotic tissue in vivo. As neither Mt-I nor Mt-II showed direct effects upon the contractile apparatus of skinned fibers, it is concluded that the mechanism of hypercontraction triggered by both myotoxins in patients involves indirect effects, i.e., the large cytosolic Ca2+ increase after sarcolemma permeabilization.

Background: Juvenile obesity is a serious problem that increases the risk of future development of cardiovascular disease and type 2 diabetes at adulthood through programing a metabolic dysfunction during development. Aim of the Work: to perform a biochemical, histological and immunohistochemical evaluation of the effect of juvenile obesity on the morphology, insulin expression, apoptosis and proliferation of the islets of Langerhans in albino rat and to evaluate the possibility of recovery at adulthood. Material and Methods: Twenty-one juvenile male albino rats were equally divided into 3 groups; control (fed 11% fat standard diet), high fat diet-induced obesity group (fed 45% fat diet for 8 weeks) and recovery group (fed 45% fat diet for 8 weeks then left for 4 weeks on standard diet). Animals were weighed and fasting blood glucose and serum insulin were quantified. Pancreatic specimens were processed for histological and immunohistochemical staining for detection of insulin, Bcl2 and Ki67. Results: Juvenile obesity group recorded a significant increase in total body weight and blood glucose coupling with a significant decrease in serum insulin. Histological examination revealed few shrunken islets of Langerhans with cells expressing nuclear alterations and cytoplasmic vacuolation. Peripheral mononuclear infiltration and dilated congested blood capillaries were observed. A significant decrease in the immunohistochemical expression of insulin, Bcl2 and Ki67 was recorded. While a significant improvement of all studied parameters was detected in the recovery group. Conclusion: Restoration of a normal diet in high fat diet-induced obesity in juvenile rats reinstated the abnormal glucose and insulin levels, ameliorated the altered morphology of islets of Langerhans, and upregulated the suppressed immunoexpression of insulin, Bcl2 and Ki67 in the islets at adulthood.