Sherif A. Abdelmottaleb Moussa

Automated assignment of NOESY NMR spectra using a knowledge based method (KNOWNOE).

Automated assignment of NOESY spectra is a prerequisite for automated structure determination of biological macromolecules. With the program KNOWNOE we present a novel, knowledge based approach to this problem. KNOWNOE is devised to work directly with the experimental spectra without interference of an expert. Besides making use of routines already implemented in AUREMOL, it contains as a central part a knowledge driven Bayesian algorithm for solving ambiguities in the NOE assignments. These ambiguities mainly arise from chemical shift degeneration which allows multiple assignments of cross peaks. Using a set of 326 protein NMR structures, statistical tables in the form of atom-pairwise volume probability distributions (VPDs) were derived. VPDs for all assignment possibilities relevant to the assignments of interproton NOEs were calculated. With these data for a given cross peak with N possible assignments Ai(i = 1,...,N) the conditional probabilities P(Ai, a|V0) can be calculated that the assignment Aidetermines essentially all (a-times) of the cross peak volume V0. An assignment Akwith a probability P(Ak, a|V0) higher than 0.8 is transiently considered as unambiguously assigned. With a list of unambiguously assigned peaks a set of structures is calculated. These structures are used as input for a next cycle of iteration where a distance threshold Dmaxis dynamically reduced. The program KNOWNOE was tested on NOESY spectra of a medium size protein, the cold shock protein (TmCsp) from Thermotoga maritima. The results show that a high quality structure of this protein can be obtained by automated assignment of NOESY spectra which is at least as good as the structure obtained from manual data evaluation.

The gold nanoparticle size and exposure duration effect on the liver and kidney function of rats: In vivo.

UNLABELLEDnNanoparticles (NPs) offer a great possibility for biomedical application, not only to deliver pharmaceutics, but also to be used as novel diagnostic and therapeutic approaches. Currently, there are no data available regarding to what extent the degree of the toxicity and the accumulation of gold nanoparticles (GNPs) are present in in vivo administration. This study aimed to address the GNP size and exposure duration effect on the liver and kidney function of rats: in vivo.nnnMETHODSnA total of 30 healthy male Wistar-Kyoto rats of the same age (12xa0weeks old) and weighing 220-240xa0g of King Saud University colony were used. Animals were randomly divided into groups, two GNP-treated rat groups and one control group (CG). The 50xa0μl of 10 and 50xa0nm GNPs was intraperitoneally administered in rats for exposure duration of 3xa0days. Then, several biochemical parameters such as aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alanine transaminase (ALT), alkaline phosphatase (ALP), urea (UREA) and creatinine (CREA) were evaluated.nnnRESULTSnIn this study, the AST values increased with the administration of 10 and 50xa0nm GNPs compared with the control. The AST values significantly increased with 10xa0nm GNPs compared with 50xa0nm GNPs and control. The GGT and ALT values decreased with the administration of 10 and 50xa0nm GNPs compared with the control. The GGT and ALT values significantly decreased with 50xa0nm GNPs compared with 10xa0nm GNPs and control. The ALP values significantly decreased with the administration of 10 and 50xa0nm GNPs compared with the control. The decrease in ALP values with 10xa0nm GNPs was higher than those compared with 50xa0nm GNPs. In this study, the levels of UREA and CREA values increased in a non significant manner after the administration of 10 and 50xa0nm GNPs compared with the control.nnnCONCLUSIONSnThis study demonstrates that the increase in the enzymes AST and the decrease in ALP are smaller GNPs (10xa0nm) size-dependent for exposure duration of 3xa0days; while the decrease in the enzymes GGT and ALT are bigger GNPs (50xa0nm) size-dependent. The levels of UREA and CREA values indicated no significant changes with the administration of 10 and 50xa0nm GNPs for exposure duration of 3xa0days compared with the control. The administration of 10 and 50xa0nm GNPs for short exposure duration of 3xa0days induced only significant variations with some liver enzymes while kidney showed no significant variations. This study suggests that synthesis and metabolism of GNPs as well as the protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.

Elucidation of the effects of a high fat diet on trace elements in rabbit tissues using atomic absorption spectroscopy

BackgroundThe mechanism of atherogenesis is not yet fully understood despite intense study in this area. The effects of high fat diet (HFD) on the changes of trace elements [iron (Fe), copper (Cu) and zinc (Zn)] in several tissues of rabbits have not been documented before. Thus, the aim of this study was to elucidate the changes in trace elements in several tissues of rabbits fed on HFD for a period of feeding of 10 weeks.ResultsThe HFD group was fed a NOR rabbit chow supplemented with 1.0% cholesterol plus 1.0% olive oil. Fe, Cu and Zn concentrations were measured in four types of tissue from control and HFD rabbits using atomic absorption spectroscopy (AAS). Comparing HFD rabbits to control rabbits, we found that the highest percentage change of increase of Fe was 95% in lung tissue, while the lowest percentage change of increase of Fe was 7% in kidney tissue; the highest percentage change of decrease of Cu was 16% in aortic tissue, while the lowest percentage change of decrease of Cu was 6% in kidney tissue; and the highest percentage change of decrease of Zn was 71% in kidney tissue, while the lowest percentage change of decrease of Zn was 8% in lung tissue.ConclusionsThese results suggest that Fe plays a major role in atherogenesis; it may accelerate the process of atherosclerosis probably through the production of free radicals, deposition and absorption of intracellular and extracellular lipids in the intima, connective tissue formation, smooth muscle proliferation, lower matrix degradation capacity and increased plaque stability. Furthermore, inducing anemia in HFD rabbits may delay or inhibit the progression of atherosclerosis. Cu plays a minor role in atherogenesis and Cu supplements may inhibit the progression of atherogenesis, perhaps by reducing the migration of smooth muscle cells from the media to the intima. Zn plays a major role in atherogenesis and that it may act as an endogenous protective factor against atherosclerosis perhaps by reducing lesion Fe content, intracellular and extracellular lipids in the intima, connective tissue formation, and smooth muscle proliferation. These results suggest that it may be possible to use the measurement of changes in trace elements in different tissues of rabbits as an important risk factor during the progression of atherosclerosis.

The biochemical changes in rats' blood serum levels exposed to different gamma radiation doses

This study aimed to address the different gamma radiations doses effect on the liver and kidney function of rats: in vivo. A total of 60 healthy male Wistar-Kyoto rats were whole body gamma irradiated with Co 60 source with 0.883 cG/sec dose rate at the beginning of the experiment. The rats were randomly divided into 4 gamma-irradiation groups (25, 50, 75 and 100 Gy) The serum levels of activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma- glutamyltransferase (GGT), UREA, creatinine (CREA) and uric acid (UAC) were measured using automated biochemical analyzer. The ALT, GGT, ALP values significantly decreased with the different gamma radiation doses compared with the control. The AST and UREA values significantly decreased after irradiation with 25 and 50 Gy gamma radiation doses compared with the control while it significantly increased with 75 and 100 Gy gamma radiation doses. The levels of CREA values decreased with no significant manner after the irradiation with gamma radiation doses compared with the control. The levels of UAC values significantly increased with 50, 75 and 100 Gy gamma radiation doses. The serum ALT and AST levels are common markers for hepatic toxicity: A lower amount of ALP indicates liver problems. The decreased CREA and the increased UAC levels might indicate development of nephritis and renal dysfunction. The excess UAC might be converted to crystals depositing in the tiny tubes of the kidney and causing acute kidney damage. It is proposed that oxidative stress is linked to the organ damage following exposure to ionizing radiation, and after the onset of oxidative stress, antioxidant treatment should be applied to delay or prevent the progression of damage.

Elucidation of the response of heavy elements levels to intraperitoneal administration of different gold nanoparticles into rats for period of 3 days in vivo

Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular, and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Gold nanoparticles (GNPs) are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to elucidate the response of heavy elements levels to intraperitoneal administration of different GNPs into rats for period of 3 daysxa0in vivo. The experimental rats were divided into normal and 3 groups (G1A, G2A and G3A; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: it means infusion of 0.05 ml of GNPs for 3 days). To investigate the role of GNP size on heavy elements [cadmium (Cd), nickel (Ni), lead (Pb) and cobalt (Co)] levels in blood and several tissues of rats, 50 µl daily dose of 10, 20 and 50 nm GNPs was intraperitonealy injected into rats for 3 days. Cd, Ni and Pb concentrations significantly increased in blood and all tissues of rats compared with the normal. Different changes were observed with Co concentrations in blood and several tissues of rats. Co concentrations significantly increased with 20 nm GNPs in blood and kidney tissue of rats compared with the normal while it significantly decreased in heart, lung and liver tissues of rats.xa010, 20 and 50 nm GNPs may be an effective inducer of oxidative stress which was evident by the fact that they caused significant increasexa0in Cd, Ni and Pb concentrations in blood and all tissues of rats compared with the normal. This study suggests that GNPs may interact with proteins and enzymes of the rats interfering with the antioxidant defense mechanism and leading to reactive oxygen species (ROS) generation, which in turn may imitate an inflammatory response and heavy element levels destruction. Exposure to intraperitoneal administration of GNPs is a potential source of oxidative stress toxicity in rats. n n xa0 n n Key words:xa0Gold nanoparticles, size, severaltissues, blood, heavy elements, toxicity, rats.

Ultraviolet-Visible and Fluorescence Spectroscopy Techniques Are Important Diagnostic Tools during the Progression of Atherosclerosis: Diet Zinc Supplementation Retarded or Delayed Atherosclerosis

Background. In this study, we examined whether UV-visible and fluorescence spectroscopy techniques detect the progression of atherosclerosis in serum of rabbits fed on high-cholesterol diet (HCD) and HCD supplemented with zinc (HCD + Zn) compared with the control. Methods. The control rabbits group was fed on 100u2009g/day of normal diet. The HCD group was fed on Purina Certified Rabbit Chow supplemented with 1.0% cholesterol plus 1.0% olive oil (100u2009g/day) for the same period. The HCD + Zn group was fed on normal Purina Certified Rabbit Chow plus 1.0% cholesterol and 1.0% olive oil supplemented with 470u2009ppm Zn for the same feeding period. UV-visible and fluorescence spectroscopy and biochemistry in Rabbits blood serum and blood hematology were measured in Rabbits blood. Results. We found that the fluorescent peak of HCD shifted toward UV-visible wavelength compared with the control using fluorescent excitation of serum at 192u2009nm. In addition, they showed that supplementation of zinc (350u2009ppm) restored the fluorescent peak closely to the control. By using UV-visible spectroscopy approach, we found that the peak absorbance of HCD (about 280u2009nm) was higher than that of control and that zinc supplementation seemed to decrease the absorbance. Conclusions. This study demonstrates that ultraviolet-visible and fluorescence spectroscopy techniques can be applied as noninvasive techniques on a sample blood serum for diagnosing or detecting the progression of atherosclerosis. The Zn supplementation to rabbits fed on HCD delays or retards the progression of atherosclerosis. Inducing anemia in rabbits fed on HCD delays the progression of atherosclerosis.

The Dimensional Hematological Alterations Induced in Blood of Rats In vivo by Intraperitoneal Administration of Gold Nanoparticles

Background: The aim of the present study was to investigate the effects of intraperitoneal administration of (Gold Nanoparticles) GNPs on the dimensional hematological alterations in rats in an attempt to cover and understand the toxicity and the potential role of GNPs as a therapeutic and diagnostic tool. Methods: A total of 30 healthy male Wistar-Kyoto rats were used in this study. Animals were randomly divided into groups, 2 GNPs-treated rats groups and one control group (NG). 2 GNPs-treated G1 and G2; received intraperitoneal administration of 50 µl of 10 and 50 nm GNPs for a period of 3 days. Hematological parameters were measured using standard hematological techniques. Results: The decrease in White Blood Cells (WBCs), Red Blood Cells (RBCs) count, monocytes%, neutrophils% and eosinophils%, observed with 10 nm GNPs was significantly higher than 50 nm GNPs and control. The lymphocytes% with 10 nm GNPs significantly increased compared with 50 nm GNPs and control. The Hemoglobin (HB) level, Hematocrit (HCT)%, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC) and Platelets (PLTs) count increased after administration of 10 and 50 nm GNPs compared with the control. The Mean Platelet Volume (MPV), Plateletcrit (PCT) and Platelet Distribution Width (PDW) significantly decreased with 50 nm GNPs compared with 10 nm GNPs and control; while Mean Corpuscular Volume (MCV) significantly increased with 50 nm GNPs. The Red blood cell Distribution Width (RDW) induced non-significant increase compared with the control. Conclusions: The decrease in RBCs count might be due to the destruction of RBCs. The increase in Hematocrit (HCT)% might be due to an increase in RBCs volume. The changes in RBCs indicates changes in morphology and deformability of RBCs, which confirmed by a slightly increase in RDW%. The significant increase in PLTs count might lead to thrombosis or aggregation of blood vessels.

Role of zinc oxide nanoparticles in alleviating hepatic fibrosis and nephrotoxicity induced by thioacetamide in rats

The present research studied the influence of zinc oxide nanoparticles (ZnO-NPs; 5, 7.5, and 10 mg/kg, i.p.) on the liver and kidney injuries motivated by thioacetamide (TAA; 100 mg/kg, i.p.). Each treatment was carried out 3 times per week for 8 weeks. ZnO-NPs relieved the decrease of hepatic or renal reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) induced by TAA. Moreover, ZnO-NPs lowered tissue malondialdehyde (MDA, an indicator for lipid peroxidation). TAA treatment led to a significant increase in plasma inflammatory markers (TNF-α, IL-6), liver enzymes (gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and kidney function parameters (creatinine, urea, uric acid). However, these parameters were reduced after treatment with ZnO-NPs. In addition, the hepatic fibrosis markers, hydroxyproline level, and α-smooth muscle actin immunopositive stain were lowered by ZnO-NPs. The protective effect of ZnO-NPs in respect to biochemical changes was also confirmed by histopathological and immunohistochemistry studies in the liver and kidney sections. Our results suggested that ZnO-NPs may attenuate TAA toxicity via suppression of oxidative stress.

Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide

BackgroundThe liver disease is one of the most important traditional public health problems in Egypt. Oxidative stress is attributed to such pathological condition that further contributes to the initiation and progression of liver injury. In the present study, we have investigated if the strong antioxidant power of Nicotinamide (NA), Vitamin B2 (VB2), and Vitamin C (VC) can ameliorate TAA-induced oxidative stress-mediated liver injury in the rats.MethodsThirty-six albino rats were divided into six groups: Control group; TAA group (IP injection with TAA at a dosage of 200xa0mg/Kg three times a week for two months); TAAu2009+u2009NA group (rats administered with NA at a dosage of 200xa0mg/kg daily besides TAA as in the control); TAAu2009+u2009VB2 group (rats administered with vitamin B2 at a dosage of 30xa0mg/kg daily besides injection with TAA); TAAu2009+u2009VC group (rats administered with vitamin C at a dosage of 200xa0mg/kg daily along with injection of TAA). TAAu2009+u2009NAu2009+u2009VBu2009+u2009VC group (rats administered the with the three vitamins daily in TAA pre-injected at the respective doses described above).ResultsTreatment of rats with TAA led to a significant elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin, cholesterol, triglycerides, low-density lipoprotein (LDL) and tumor necrosis factor-alpha (TNF-α) in the serum samples. Moreover, malondialdehyde (MDA), hydroxyproline and nitic oxide (NO) were also significantly increased in the TAA-treated rats, while reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were significantly compromised in the hepatic samples. Rats administered with NA, VB2, and VC as individually or in combination ameliorated the deleterious effects of TAA that was confirmed by histopathology. However, the combination of the three vitamins was found more effective as compared to each of the vitamins.ConclusionOur work demonstrates that NA, VB2, and VC cross-talk with each other that act as a more potent biochemical chain of antioxidant defense against TAA-induced toxicities in vivo.

Effect of melanin on gold nanoparticle-induced hepatotoxicity and lipid peroxidation in rats

Introduction Melanin pigments are produced by melanocytes and are believed to act as antioxidants based on the belief that melanin can suppress electronically stirred states and scavenge the free radicals. Materials and methods The study was aimed to verify and prove the toxicity induced by administration of gold nanoparticles (GNPs) and to characterize the role of melanin as an antioxidant against inflammatory liver damage, oxidative stress, and lipid peroxidation induced intraperitoneally by GNPs in vivo. Results The findings from this study confirmed that administration of GNPs intraperitoneally caused liver damage in addition to producing oxidative stress and fatty acid peroxidation. The treatment of rats with melanin along with GNPs induced dramatic changes in all the measured biochemical parameters. Our data demonstrated that melanin completely inhibited inflammatory liver damage, oxidative stress, and lipid peroxidation, which was confirmed by the histological investigation of different liver sections stained by H&E. Conclusion These results suggest the beneficial use of melanin together with GNPs for alleviating its toxicity. Other studies should be implemented taking into consideration the role of melanin in comparison with other natural antioxidants.