Nω-Nitro-L-Arginine Methylester Ameliorates Myocardial Toxicity Induced by Doxorubicin

Mansour, Mahmoud Ahmed,El-Din, Ayman Gamal,Nagi, Mahmoud N.,Al-Shabanah, Othman A.,Al-Bekairi, Abdullah M. Korean Society for Biochemistry and Molecular Biol 2003 Journal of biochemistry and molecular biology Vol.36 No.6

The effects of $N{\omega}$-nitro-L-arginine methylester (L-NAME) and L-arginine on cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single dose of Dox 15 mg/kg i.p. induced cardiotoxicity, manifested biochemically by a significant elevation of serum creatine phosphokinase (CPK) activity [EC 2.7.3.2]. Moreover, cardiotoxicity was further confirmed by a significant increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water 5 days before and 3 days after the Dox injection significantly ameliorated the cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity and lipid peroxides in the cardiac tissue homogenates. On the other hand, the administration of L-arginine 70 mg/kg/d p.o. did not protect the cardiac tissues against the toxicity that was induced by the Dox treatment. The findings of this study suggest that L-NAME can attenuate the cardiac dysfunction that is produced by the Dox treatment via the mechanism(s), which may involve the inhibition of the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy for cardiotoxicity that is induced by Dox and can then be used to improve the therapeutic index of Dox.

Synthesis, Spectroscopic, and Biological Studies of Chromium(III), Manganese(II), Iron(III), Cobalt(II), Nickel(II), Copper(II), Ruthenium(III), and Zirconyl(II) Complexes of N¹,N²-Bis(3-((3-hydroxynaphthalen-2-yl)methylene-amino)pr

Al-Hakimi, Ahmed N.,Shakdofa, Mohamad M.E.,El-Seidy, Ahemd M.A.,El-Tabl, Abdou S. Korean Chemical Society 2011 대한화학회지 Vol.55 No.3

[ $N^1,N^2$ ]bis(3-((3-hydroxynaphthalen-2-yl)methylene-amino)propyl)phthalamide ($H_4L$, 1) 의 새로운 크롬(III), 망간(II), 철(III), 코발트(II), 니켈(II), 구리(II), 루테늄(III) 및 산화 지르코늄(II) 착물을 합성하여 원소분석, 물리적 성질 및 분광학적으로 특성을 규명하였다. 분광학적 결과를 통해 이 리간드는 $[H_4LMX_2(H_2O)]{\cdot}nH_2O$ (M = Cu(II), Ni(II), Co(II), X = Cl 또는 $NO_3$)의 일반식을 갖는 착물2-5에서는 중성의 삼배위 리간드로 행동한다. 또는 $[H_4L(ZrO)_2Cl_2]{\cdot}8H_2O$ 의 일반식을 갖는 착물 6-9 에서는 이염기성 육배위 리간드로 행동한다. DMF 용액에서의 몰전기전도도 실험결과 이들 착물은 비이온성을 나타낸다. 고체 구리착물 2, 5 및 6 의 ESR 스펙트럼에서 $g_{\parallel}$ >g> $g_e$을 보이는데, 이는 일그러진 팔면체구조와 큰 공유결합성을 갖는 $d{_x}^2{_{-y}}^2$ 오비탈에 비공유 전자쌍이 존재함을 의미한다. 이합체 구리(II) 착물 $[H_2LCu_2Cl_2(H_2O)_4]{\cdot}3H_2O$ (6)에 대해 두 구리원자 사이의 거리를 ESR 스펙트럼으로부터 추정한 parallel component 의 field zero splitting 파라메타를 이용하여 계산하였다. 이들 화합물의 항박테리아 및 항균 활성도를 측정한 결과, 몇가지 금속 착물의 경우 표준시약인 tetracycline (박테리아) 및 Amphotricene B (균류)보다 더 큰 저해효과를 보였다. Novel chromium(III), manganese(II), iron(III), cobalt(II), nickel(II), copper(II), ruthenium(III), and zirconyl(II) complexes of $N^1,N^2$-bis(3-((3-hydroxynaphthalen-2-yl)methylene-amino)propyl)phthalamide ($H_4L$, 1) have been synthesized and characterized by elemental, physical, and spectral analyses. The spectral data showed that the ligand behaves as either neutral tridentate ligand as in complexes 2-5 with the general formula $[H_4LMX_2(H_2O)]{\cdot}nH_2O$ (M=Cu(II), Ni(II), Co(II), X = Cl or $NO_3$), neutral hexadentate ligand as in complexes 10-12 with the general formula $[H_4LM_2Cl_6]{\cdot}nH_2O$ (M=Fe(III), Cr(III) or Ru(III)), or dibasic hexadentate ligand as in complexes 6-9 with the general formula $[H_2LM_2Cl_2(H_2O)_4]{\cdot}nH_2O$ (M = Cu(II), Ni(II), Co(II) or Mn(II), and 13 with general formula $[H_4L(ZrO)_2Cl_2]{\cdot}8H_2O$. Molar conductance in DMF solution indicated the non-ionic nature of the complexes. The ESR spectra of solid copper(II) complexes 2, 5, and 6 showed $g_{\parallel}$ >g> $g_e$, indicating distorted octahedral structure and the presence of the unpaired electron in the $N^1,N^2$ orbital with significant covalent bond character. For the dimeric copper(II) complex $[H_2LCu_2Cl_2(H_2O)_4]{\cdot}3H_2O$ (6), the distance between the two copper centers was calculated using field zero splitting parameter for the parallel component that was estimated from the ESR spectrum. The antibacterial and antifungal activities of the compounds showed that, some of metal complexes exhibited a greater inhibitory effect than standard drug as tetracycline (bacteria) and Amphotricene B (fungi).

Nω-Nitro-L-Arginine Methylester Ameliorates Myocardial Toxicity Induced by Doxorubicin

( Mahmoud Ahmed Mansour ),( Ayman Gamal El Din ),( Mahmoud N. Nagi ),( Othman A. Al Shabanah ),( Abdullah M. Al Bekairi ) 생화학분자생물학회 2003 BMB Reports Vol.36 No.6

The effects of No-nitro-L-arginine methylester (L-NAME) and L-arginine on cardiotoxicity that is induced by doxorubicin (Dox) were investigated. A single dose of Dox 15mgkg i.p. induced cardiotoxicity, manifested biochemically by a significant elevation of serum creatine phosphokinase (CPK) activity [EC 2.7,3.2]. Moreover, cardiotoxicity was further confirmed by a significant increase in lipid peroxides, measured as malon-di-aldehyde (MDA) in cardiac tissue homogenates. The administration of L-NAME 4 mg/kg/d p.o. in drinking water 5 days before and 3 days after the Dox injection significantly ameliorated the cardiotoxic effects of Dox, judged by the improvement in both serum CPK activity and lipid peroxides in the cardiac tissue homogenates. On the other hand, the administration of L-arginine 70mg/kg/d p.o. did not protect the cardiac tissues against the toxicity that was induced by the Dox treatment. The findings of this study suggest that L-NAME can attenuate the cardiac dysfunction that is produced by the Dox treatment via the mechanism(s), which may involve the inhibition of the nitric oxide (NO) formation. L-NAME may, therefore, be a beneficial remedy for cardiotoxicity that is induced by Dox and can then be used to improve the therapeutic index of Dox.

Larvicidal activity of leaf extract of Nerium oleander L. and its synthesized metallic nanomaterials on dengue vector, Aedes aegypti

Al‐Hakimi Ahmed N.,Abdulghani Mahfoudh A.M.,Alhag Sadeq K.,Aroua Lotfi M.,Mahyoub Jazem A. 한국곤충학회 2022 Entomological Research Vol.52 No.3

The development of natural insecticide from plant products may have a beneficial effect as a promising candidate for practical strategies for controlling vector-borne diseases without current treatment. The present study was carried out to characterize green synthesized metallic nanomaterials for silver (Ag-NPs) and gold (Au-NPs) from extract leaf of Nerium oleander L., assess in vivo toxicity, and evaluate the larvicidal activity against Aedes aegypti. The prepared nanomaterials (Ag-NPs and Au-NPs) were characterized by Ultraviolet–Visible Spectroscopy (UV–Vi s ) , F o u r i e r transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and transmission electron microscopy (TEM). In addition, the subacute in vivo toxicity method was used to assess the extract and the nanomaterials (Ag-NPs and Au-NPs); in evaluating larvicidal activities using the World Health Organization (WHO) method. The Ag-NPs and Au-NPs were confirmed by shifting the absorption band in UV–Vi s , FTIR spectrums toward higher wavelengths. TEM and XRD analysis were revealed that the average particle size of Au-NPs and Ag-NPs showed 15.30 and 11.48 nm, respectively. In the toxicity experiment, no mortality or signs of toxicity were reported in all groups of treated animals; in larvicidal activity, the Au-NPs and Ag-NPs with LC50 36.0716 and 46.645 ppm respectively showed more effectiveness than leaf extract alone 108.1665 ppm. Collectively, extract leaf of N. oleander L. can be efficiently used to synthesize metallic nanomaterials with silver and gold, which can be adopted as a natural source of insecticide against Ae. aegypti.

Novel Syntheses of 5-Aminothieno[2,3-c]pyridazine, Pyrimido[4',5':4,5]thieno[2,3-c]pyridazine, Pyridazino[4',3':4,5]thieno-[3,2-d][1,2,3]triazine and Phthalazine Derivatives

El Gaby, Mohamed S.A.,Kamal El Dean, Adel M.,Gaber, Abd El Aal M.,Eyada, Hassan A.,Al Kamali, Ahmed S.N. Korean Chemical Society 2003 Bulletin of the Korean Chemical Society Vol.24 No.8

Condensation of 4-cyano-5,6-dimethyl-3-pyridazinone 1 with aromatic aldehydes gave the novel styryl derivatives 2a-c. Refluxing of compound 2a with phosphorus oxychloride furnished 3-chloropyridazine derivative 3. Compound 3 was reacted with thiourea and produced pyridazine-3(2H)thione 4. Thieno[2,3-c]- pyridazines 5a-e were achieved by cycloalkylation of compound 4 with halocompounds in methanol under reflux and in the presence of sodium methoxide. Also, refluxing of compound 4 with N-substituted chloroacetamide in the presence of potassium carbonate afforded thienopyridazines 6a-e. Cyclization of compound 6 with some electrophilic reagents as carbon disulfide and triethyl orthoformate furnished the novel pyrimido[4',5':4,5]thieno[2,3-c]pyridazines 12 and 13a-c, respectively. Diazotisation of compound 6 with sodium nitrite in acetic acid produced the pyridazino[4',3':4,5]thieno[3,2-d][1,2,3]triazines 14a-c. Ternary condensation of compound 1, aromatic aldehydes and malononitrile in ethanol containing piperidine under reflux afforded the novel phthalazines 16a-c. Compound 3 was subjected to some nucleophilic substitution reactions with amines and sodium azide and formed the aminopyridazines 17a, b and tetrazolo[1,5-b]-pyridazine 19, respectively. The structures of the synthesized compounds were established by elemental and spectral analyses.

Biological Screening of Novel Derivatives of Valproic Acid for Anticancer and Antiangiogenic Properties

Farooq, Muhammad,El-Faham, Ayman,Khattab, Sherine N.,Elkayal, Ahmed M.,Ibrahim, Mahmoud F.,Taha, Nael Abu,Baabbad, Almohannad,Wadaan, Mohammad A.M.,Hamed, Ezaat A. Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Background: Valproic acid (VPA) is a potent anticancer and antiangiogenic agent. However, design and synthesis of chemical derivatives with improved antiangiogenic and anticancer activities are still necessary. In this study a library of novel derivatives of VPA was synthesized and tested. Methods: A human liver cancer cell line (HepG2) and a human normal embryonic kidney cell line (HEK 293) were exposed to various concentrations of VPA derivatives for 24 hours and cell viability was checked by MTT colorimetric assay. Anti-angiogenic properties were evaluated in transgenic zebrafish embryos. Results: N-valproylglycine derivatives suppressed survival almost 70% (p value 0.001) in HepG2 cells but only 10-12% in HEK 293 cells (p value 0.133). They also suppressed angiogenic blood vessel formation by 80% when used between $2-20{\mu}M$ in zebrafish embryos. Valproic acid hydrazides showed moderate level of anticancer activity by affecting 30-50% (p value 0.001) of cell viability in HepG2 cells and 8-10% in HEK293 cells (p value 0.034). Conclusion: The majority of compounds in this study showed potent and stronger antiangiogenic and anticancer activity than VPA. They proved selectively toxic to cancer cells and safer for normal cells. Moreover, these compounds inhibited developmental angiogenesis in zebrafish embryos. Based on the fact that liver is a highly vascularized organ, in case of liver carcinoma these compounds have the potential to target the pathological angiogenesis and could be an effective strategy to treat hepatocellular carcinoma.

Implications of Sex Hormone Receptor Gene Expression in the Predominance of Hepatocellular Carcinoma in Males: Role of Natural Products

Ahmed, Hanaa H,Shousha, Wafaa Gh,Shalby, Aziza B,El-Mezayen, Hatem A,Ismaiel, Nora N,Mahmoud, Nadia S Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

Endotoxins of Enteric Pathogens Are Chemotactic Factors for Human Neutrophils

(Laila N. Islam),(A. H. M. Nurun Nabi),(K. Mokim Ahmed),(Novera Sultana) 생화학분자생물학회 2002 BMB Reports Vol.35 No.5

Early activation of human peripheral blood polymorphonudear neutrophils is characterized by their morphological changes from spherical to polarized shapes. The endotoxins from enteric pathogens (S. dysenteriae type 1, V cholerae Inaba 569B, S. typhimurium, and K. pneumoniae) were assessed by their ability to induce morphological polarization of the neutrophils as measures of early activation. Phagocytic activity, adhesion, chemokinetic locomotion, and nitroblue tetrazolium (NBT) dyereduction ability measured the later activation of the cells. Neutrophils showed distinct morphological polarization in suspension over a wide range of concentrations of these endotoxins when were compared with those that were induced by the standard chemotactic factor, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It was discovered that all of the endotoxins induced locomotor responses in neutrophils in suspension that were dose- and time-dependent. The optimum concentration for the endotoxins of S. dysenteriae, V. cholerae, and K pneumoniae was 1 mg/ml in which 71, 69, and 66% of the neutrophils were polarized. However, the S. typhimurium dose was 2 mg/ml in which 50% of the cells responded. Neutrophils that were stimulated with endotoxins also showed increased random locomotion (p<0.005) through cellulose nitrate filters, but an enhanced adhesion of the cells to glass surfaces (p<0.03). These are important functions of these cells to reach and phagocytose damaged cells, as well as invading microorganisms. Interestingly, the endotoxins had a highly-significant inhibitory effect upon the proportions of neutrophils phagocytosing opsonized yeast (p<0.01) with a small number of yeast that were engulfed by the cells (p<0.02). Further, endotoxin-treated cells showed an enhanced ability to reduce NBT dye (p<0.03). Therefore, we concluded that endotoxins of enteric pathogens are neutrophil chemotactic factors.

Endotoxins of Enteric Pathogens Are Chemotactic Factors for Human Neutrophils

Islam, Laila N.,Nabi, A.H.M. Nurun,Ahmed, K. Mokim,Sultana, Novera Korean Society for Biochemistry and Molecular Biol 2002 Journal of biochemistry and molecular biology Vol.35 No.5

Early activation of human peripheral blood polymorphonuclear neutrophils is characterized by their morphological changes from spherical to polarized shapes. The endotoxins from enteric pathogens (S. dysenteriae type 1, V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae) were assessed by their ability to induce morphological polarization of the neutrophils as measures of early activation. Phagocytic activity, adhesion, chemokinetic locomotion, and nitroblue tetrazolium (NBT) dye-reduction ability measured the later activation of the cells. Neutrophils showed distinct morphological polarization in suspension over a wide range of concentrations of these endotoxins when were compared with those that were induced by the standard chemotactic factor, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It was discovered that all of the endotoxins induced locomotor responses in neutrophils in suspension that were dose- and time-dependent. The optimum concentration for the endotoxins of S. dysenteriae, V. cholerae, and K. pneumoniae was 1 mg/ml in which 71, 69, and 66% of the neutrophils were polarized. However, the S. typhimurium dose was 2 mg/ml in which 50% of the cells responded. Neutrophils that were stimulated with endotoxins also showed increased random locomotion (p<0.005) through cellulose nitrate filters, but an enhanced adhesion of the cells to glass surfaces (p<0.03). These are important functions of these cells to reach and phagocytose damaged cells, as well as invading microorganisms. Interestingly, the endotoxins had a highly-significant inhibitory effect upon the proportions of neutrophils phagocytosing opsonized yeast (p<0.01) with a small number of yeast that were engulfed by the cells (p<0.02). Further, endotoxin-treated cells showed an enhanced ability to reduce NBT dye (p<0.03). Therefore, we concluded that endotoxins of enteric pathogens are neutrophil chemotactic factors.

Biochar, a potential hydroponic growth substrate, enhances the nutritional status and growth of leafy vegetables

Awad, Y.M.,Lee, S.E.,Ahmed, M.B.M.,Vu, N.T.,Farooq, M.,Kim, I.S.,Kim, H.S.,Vithanage, M.,Usman, A.R.A.,Al-Wabel, M.,Meers, E.,Kwon, E.E.,Ok, Y.S. Butterworth-Heinemann, Ltd 2017 Journal of cleaner production Vol.156 No.-

A hydroponics system developed using a nutrient film technique was used to evaluate the effectiveness of rice husk biochar (RB) alone or in combination with perlite (PL) as substrates for increasing the growth of leafy vegetables compared with that of PL. Seedlings of cabbage, dill, mallow, red lettuce, and tatsoi were grown hydroponically in PL, RB, and PL + RB (1:1 ratio of PL to RB, v/v) substrates for a 30-d under optimal environmental conditions in a greenhouse. Shoot length and fresh/dry masses of cabbage, dill, and red lettuce plants grown in RB substrate were decreased by 49% on average compared to those plants grown in PL substrate. In contrast, PL + RB substrate led to approximately 2-fold increases in shoot length, number of leaves, and fresh/dry masses of leafy vegetable plants compared with those grown in PL substrate. Foliar nutritional composition (Ca, Mg, K, Na, Mn, Fe, and Zn) and nitrogen status (SPAD index) of plants grown in PL + RB and PL substrates suggested the presence of optimal growth conditions for ensuring optimum yield with high quality. In addition, RB substrate contributed to respective increases of 1.2-3.5-fold in leaf K, Mg, Mn, and Zn contents in most vegetable plants compared with those grown in PL substrate. The RB alone or in combination with PL substrates decreased algal growth in the nutrient solutions as confirmed by scanning electron micrographs of microalgae on the RB surface. The results also indicated that use of PL + RB hydroponic substrate could be an alternative and effective technology for the better management of unwanted algal growth in nutrient solutions and high production of leafy vegetables.