Khalid S. Hashem

The protective effects of cerium oxide nanoparticles against hepatic oxidative damage induced by monocrotaline.

Objective The objective of the present study was to determine the ability of cerium oxide (CeO2) nanoparticles to protect against monocrotaline (MCT)-induced hepatotoxicity in a rat model. Method Twenty male Sprague Dawley rats were arbitrarily assigned to four groups: control (received saline), CeO2 (given 0.0001 nmol/kg intraperitoneally [IP]), MCT (given 10 mg/kg body weight IP as a single dose), and MCT + CeO2 (received CeO2 both before and after MCT). Electron microscopic imaging of the rat livers was carried out, and hepatic total glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPX), glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) enzymatic activities were quantified. Results Results showed a significant MCT-induced decrease in total hepatic GSH, GPX, GR, and GST normalized to control values with concurrent CeO2 administration. In addition, MCT produced significant increases in hepatic CAT and SOD activities, which also ameliorated with CeO2. Conclusions These results indicate that CeO2 acts as a putative novel and effective hepatoprotective agent against MCT-induced hepatotoxicity.

Deltamethrin-induced oxidative stress and biochemical changes in tissues and blood of catfish ( Clarias gariepinus ): antioxidant defense and role of alpha-tocopherol

BackgroundThe pyrethroid class of insecticides, including deltamethrin, is being used as substitutes for organochlorines and organophosphates in pest-control programs because of their low environmental persistence and toxicity. This study was aimed to investigate the impact of commonly used pesticides (deltamethrin) on the blood and tissue oxidative stress level in catfish (Clarias gariepinus); in addition to the protective effect of α-tocopherol on deltamethrin induced oxidative stress.Catfish were divided into three groups, 1st control group include 20 fish divided into two tanks each one contain 10 fish, 2nd deltamethrin group, where Fish exposed to deltamethrin in a concentration (0.75 μg/l) and 3rd Vitamin E group, Fish exposed to deltamethrin and vitamin E at a dose of 12 μg/l for successive 4 days.Serum, liver, kidney and Gills were collected for biochemical assays. Tissue oxidative stress biomarkers malondialdhyde (MDA) and catalase activity in liver, kidney and gills tissues, serum liver enzymes (ALT and AST), serum albumin, total protein, urea and creatinine were analysed.ResultsOur results showed that 48 h. exposure to 0.75 μg/l deltamethrin significantly (p < 0.05) increased lipid peroxidation (MDA) in the liver, kidney and gills while catalase activity was significantly decreased in the same tissues. This accompanied by significant increase in serum ALT, AST activity, urea and creatinine and a marked decrease in serum albumin and total proteins.ConclusionsIt could be concluded that deltamethrin is highly toxic to catfish even in very low concentration (0.75 μg/l). Moreover the effect of deltamethrin was pronounced in the liver of catfish in comparison with kidneys and gills. Moreover fish antioxidants and oxidative stress could be used as biomarkers for aquatic pollution, thus helping in the diagnosis of pollution. Adminstration of 12 μg/l α-tocopherol restored the quantified tissue and serum parameters, so supplementation of α-tocopherol consider an effective way to counter the toxicity of deltamethrin in the catfish.

The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid.

Background Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. Objective The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Design Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 μg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3–20 nm) 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Materials and methods Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4]) and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]). Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E) and Masson’s trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. Results The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species. This was shown by the significant decrease in free T3 and T4 and GSH levels, which was accompanied by significant increases in catalase, SOD, and MDA in the chromium-treated group compared to the control group. Se nanoparticles have a protective effect on K2Cr2O7-induced thyroid damage, as a result of correcting the free T3 and T4 levels and GSH, catalase, SOD, and MDA compared to the K2Cr2O7-treated group. Administration of nano-selenium alone in the nano-selenium-treated group had no toxic effect on rats’ thyroid compared to the control group. The biochemical results were confirmed by histopathological, immunohistochemical and pathomorphological studies.

Cerium oxide nanoparticles alleviate oxidative stress and decreases Nrf-2/HO-1 in D-GALN/LPS induced hepatotoxicity.

Translocation of the master regulator of antioxidant-response element-driven antioxidant gene, nuclear factor erythroid 2 (Nrf-2) from the cytoplasm into the nucleus and triggering the transcription of hemoxygenase-1 (HO-1) to counteract the oxidative stress is a key feature in D-galactoseamine and lipopolysaccharide (D-GALN/LPS) induced hepatotoxicity. We mainly aimed to study the effect of cerium oxide (CeO2) nanoparticles on Nrf-2/HO-1 pathway whereas; it has previously shown to have an antioxidant effect in liver models. Administration of CeO2 nanoparticles significantly decreased the translocation of the cytoplasmic Nrf-2 with a concomitant decrement in the gene expression of HO-1 as it reveals a powerful antioxidative effect as indicated by the significant increase in the levels of glutathione (GSH), glutathione peroxidase (GPX1), glutathione reductase (GR), superoxide dismutase (SOD) and catalase. In synchronization, a substantial decrement in the levels of inducible nitric oxide synthase (iNOS), TBARS and percentage of DNA fragmentation was established. These results were confirmed by histopathology examination which showed a severe degeneration, haemorrhages, widened sinusoids and focal leukocyte infiltration in D-GALN/LPS treatment and these features were alleviated with CeO2 administration. In conclusion, CeO2 is a potential antioxidant that can effectively decrease the translocation of the cytoplasmic Nrf-2 into the nucleus and decrease HO-1 in D-GALN/LPS induced hepatotoxicity.

Possible Therapeutic Effect of Stem Cell in Atherosclerosis in Albino Rats. A Histological and Immunohistochemical Study.

Background Atherosclerosis is the leading cause of death worldwide. there are no effective approaches to regressing atherosclerosis due to not fully understood mechanisms. Recently, stem cell-based therapies have held promises to various diseases, including vascular diseases. Aim The present study aimed at investigating the possible effect of cord blood mesenchymal stem cell (MSC) therapy on atherosclerosis. Material and Methods Eighty adult male albino rats were divided into control group (I), atherogenic group (II): subjected to high cholesterol fed diet (200~300 mg/kg body weight) for 12 weeks and 1.8 million units of vitamin D / kg of diet for 6 weeks. Stem cell therapy group (III): injected with stem cells in the tail vein following confirmation of atherosclerosis. Histological, Immunohistochemical and morphometric studies were performed were conducted. Results Atherogenic group (II) showed increased aortic thickness, intimal proliferation, smooth muscle proliferation and migration. Increased area % of collagen fibers, iNOS and vimentin immunoreactions were recorded and proved morphometrically. All findings regressed on stem cell therapy. Conclusion A definite therapeutic effect of mesenchymal stem cells was found on atherosclerosis.

Oxidative hepatotoxicity effects of monocrotaline and its amelioration by lipoic acid, S-adenosyl methionine and vitamin E

Abstract Liver is the major site for several xenobiotics metabolism, and formation of toxic metabolites that may be hepatotoxic, therefore the burden of metabolism and exposure to dangerous chemicals make liver vulnerable to a variety of disorders. Our work aimed to investigate the effects of some antioxidants such as lipoic acid (LA), S-adenosyl methionine (SAM) and vitamin E in a trail to investigate the possibility of using these substances to relieve and protect liver from exposure to monocrotaline (MCT). Twenty-five mature adult rats were classified into five groups (five rats in each group), control group, MCT-induced hepatic damage, LA+MCT, SAM+MCT and vitamin E+MCT group. Homogenates of liver samples were used for measuring the oxidative biomarkers and hepatic antioxidant status. The results showed that administration of vitamin E, SAM and LA caused a significant increase in liver glutathione contents, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and a significant decrease in hepatic catalase and superoxide dismutase. We could conclude that administration of natural LA, SAM and vitamin E before and after MCT injection modulate the hepatic oxidative stresses induced by MCT in various extents.

The effect of aspirin nanoemulsion on TNFα and iNOS in gastric tissue in comparison with conventional aspirin

Background No dose of aspirin is free of bleeding risk. Even at a dose as low as 75 mg/day, the risk of upper gastrointestinal bleeding is twice as high as among nonusers. Nanoemulsions (NEs) are emulsion systems with droplet size in nanometer scale in which oil or water droplets are finely dispersed in the opposite phase with the help of a suitable surfactant to stabilize the system. Objectives The objective of this study was to determine the effect of aspirin NE in comparison to conventional aspirin. Materials and methods A total of 24 male rats were used in the study and arbitrarily assigned to four groups. Group 1 was the control group, and was given saline. Group 2 was given blank NE 1.5 mL/kg orally. Group 3 was given aspirin 30 mg/kg body weight orally. Group 4 was given aspirin NE 30 mg/kg body weight orally. Rats were killed, and gastric tissue was quickly excised after dissection of the animals. The tissues were divided into three pieces. The first one was kept in formalin 10% for pathological investigation. The second piece was kept in liquid nitrogen for molecular investigation. The third piece was homogenized in ten volumes of ice-cold phosphate-buffered saline (pH 7) using a Teflon homogenizer until a uniform suspension was obtained. The homogenate was centrifuged at 4,000 rpm for 30 minutes at 4°C to separate the supernatant from cellular debris. The supernatant was then used for the estimation of biochemical assays. Results The present study shows that aspirin has a toxic effect on the stomach as a result of inducing marked oxidative damage and the release of reactive oxygen species. This was shown by the significant increase in TNFα, iNOS, prostaglandin E2, and malondialdehyde levels, and also a significant decrease in glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase. In the aspirin-treated group compared to the control group, the NE had a protective effect on the stomach and caused less injury than aspirin, indicated by significant decreases in TNFα, iNOS, prostaglandin E2, and malondialdehyde levels, and also significant increases in glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase. The biochemical results were confirmed by histopathological studies. Conclusion Aspirin nanoemulsion has less toxic effect on the gastric mucosa compared to ordinary aspirin. This can be indicated by the increase of the antioxidant activity and the decrease of the inflammatory mediators in the gastric tissue.