Publications

  • Mahmoud E Balbaa
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    ABSTRACT: Aims: It is to screen many natural product extracts for their in vitro and in vivo effects on the activities of hepatic α-amylase and α-glucosidase to validate their biological importance. Study Design: Different groups of non-diabetic and diabetic rats were treated by different plants for the in vivo study of glycosidases. In vitro effect of the plants on the tested enzymes was studied in presence and absence of their aqueous extract. Place and Duration of Study: Department of Biological & Environmental Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon, between March 2013 and February 2014. Methodology: Enzymes were extracted from the livers of normal rats, also the natural products extracts were prepared for the in vitro studies. α-Amylase and α-glucosidase assays were done in the presence and absence of each plant extract. For the in vivo studies, normal non-diabetic rats were divided into groups, whereas the first group is a control that includes rats fed on normal food diet. The other groups include rats fed on normal food diet mixed with the tested plant leaves (20 mg/g body weight/day) Diabetes was induced in diabetic rats by single intraperitonial injection of streptozotocin. Diabetic rats were divided into groups and treated like the non-diabetic rats. Results: Only Thymus vulgaris and Origanum vulgare extracts showed a significant in vitro dosedependent inhibition on α-amylase with IC50 values of 0.2±0.01 and 0.37±0.03mg/ml, respectively. However, the in vivo effect was not detected for four weeks treatment for the two enzymes. The in vitro treatment of α-amylase by Thymus vulgaris and Origanum vulgare extracts exhibited a mixedtype inhibition. Moreover, the in vivo inhibition of both extracts on the tested hepatic enzymes was not detected in streptozotocin-induced diabetic rats fed on Thymus vulgaris and Origanum vulgare for four weeks. Blood sugar level was non-significantly decreased with respect to that of nontreated rats. Conclusion: some non anti-diabetic plant extracts possess an in vitro inhibition of glycosidases.
    International Journal of Biochemistry Research. 10/2014;
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    ABSTRACT: This study included 20 selected female patients with breast cancer, 30 of their female relatives (sisters and daughters), and 10 healthy females as a control group. Genomic DNA was extracted from peripheral blood lymphocytes of all the subjects, and the polymerase chain reaction was carried out using specific primers for BRCA1 (exons 2 and 8) and BRCA2 (exons 9, 11, and 21). The mutations were detected using a single-strand conformation polymorphism assay and heteroduplex analysis. Finally, the sample variants and their controls were sequenced. Mutations were detected in 44% of the study population, with 18% found in the BRCA1 gene and 26% attributed to BRCA2. Five sequence variants were identified, including two frameshift mutations, one nonsense mutation, and two missense mutations. Therefore, we conclude that germline mutations in two major genes, BRCA1 and BRCA2, may have an important influence on the predisposition and development of familial breast cancer.
    Biochemical Genetics 02/2014; 52(1-2):15-28. · 0.94 Impact Factor
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    ABSTRACT: In this article, we present a study on the levels of epidermal growth factor (EGF), its phosphorylated receptor (p-EGFR) and transforming growth factor-β1 (TGF-β1) in the sera of patients with hepatocellular carcinoma (HCC) and chronic hepatitis C (CHC) infection. The results reveal significant higher serum levels of EGF and TGF-β1 in patients with HCC compared to their level in patients with CHC infection and control subjects. The levels of p-EGFR in HCC and CHC patients show a highly significant difference between patients. Based on the best cutoff value of 914 pg/ml, EGF shows 63.3 % sensitivity and 87.5 % specificity for HCC patients where the area under the curve is 0.81. The p-EGFR shows sensitivity of 63.3 % and specificity of 100 % where the area under the curve is 0.87 for HCC patients based on the best cutoff value of 39 U/mg protein. The best cutoff value (370 pg/ml) for serum TGF-β1 displays sensitivity of 86.7 % and specificity of 100 %, where the area under the curve is 0.97 for HCC patients.
    Medical Oncology 09/2013; 30(3):673. · 2.14 Impact Factor
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    ABSTRACT: Coccidiosis is one of the most common parasitic diseases affecting many species of domestic animals. This disease has a major economic significance and the search for new compounds having anticoccidial activity is of great importance. In this article, different levels of protection from coccidian infection by Eimeria stiedae were developed in rabbits by treatment with compounds incorporating the skeleton of thiourea. These compounds include 4,5-diphenylimidazole-2-thione (1), 4,5-Diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-Hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) compared to the anticoccidial drug toltrazuril as a reference compound. Compounds 1-3 inhibit coccidiosis-induced activity of α-glucosidase. The protection from coccidial infection by compound 1 was higher than that shown for compounds 2 and 3. These data suggest that diazole and triazole thione derivatives have a mimetic effect for anticoccidial drugs through their inhibition of glycosidases.
    Acta biochimica Polonica 10/2012; · 1.19 Impact Factor
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    MAHMOUD BALBAA and EL SAYED H. EL ASHRY
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    ABSTRACT: The enzyme inhibition is valuable in the regulation of the enzyme activity. It has many applications, which include the drug design to target an enzyme. In the present review, we focus on the inhibition of different enzymes such as glycosidases, arylsulfatases and others by synthetic inhibitors or drugs. This provides the strategy that combines the inhibitory and therapeutic mode of action of the confirmed inhibitors.
    Biochemistry & Physiology: Open Access. 01/2012; 1(2).
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    Natalia El-Merhie, Ismail Sabry, Mahmoud Balbaa
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    ABSTRACT: Calcium is an essential nutrient required for critical biological functions. Calcium supplementation is to be evaluated using immature female rats. The present study focused on some blood parameters, gonadal development and bone structure. Forty immature female Sprague-Dawley rats were randomly divided into four equal-sized groups (80 g average body weight) to receive calcium chloride dihydrate (group I: control; groups II, III and IV: received 20 mg, 40 mg and 60 mg per kg body weight, respectively) for 5 weeks. Rats were decapitated, and their trunk blood was sampled for biochemical assays. Cholesterol, triglycerides, glucose and calcium were measured. Gonadal and bone structure were histologically evaluated. Results revealed that treatment of developing female rats with three calcium doses used have no marked effect on the serum calcium and cholesterol levels. However, serum triglyceride level and body weight gain are significantly decreased in rats treated with all of the three calcium doses. Serum glucose level showed a marked increase in animals treated with the higher calcium doses. Moreover, observable histological alterations are recognized in the ovaries. Bones of the experimental animals also showed morphological alterations. These results suggest that increasing calcium supplementation decreases triglycerides and percentage body weight gain and positively affects the bone and gonadal development.
    Journal of physiology and biochemistry 12/2011; 68(2):219-27. · 1.65 Impact Factor
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    ABSTRACT: Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM1*0/*0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A1*2A and CYP2E1*6 alone are not significantly associated with GI cancer development, although CYP1A1*2A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A1*2A/*2A combined with GSTM1*0/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.
    Genetic Testing and Molecular Biomarkers 06/2011; 15(6):423-9. · 1.44 Impact Factor
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    ABSTRACT: The in vivo and in vitro effects of 4,5-diphenylimidazole-2-thione (1), 4,5-diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) on α-glucosidase and α-amylase were investigated. The in vivo inhibition has been found to be dose-dependent and to occur at a value less than LD50. The in vitro treatment of the enzymes by 4,5-diphenylimidazole-2-thione exhibited a reversible inhibition of the non-competitive type with Ki value of 3.5 and 6.5×10(-5) M for α-glucosidase and α-amylase, respectively. 4,5-diphenyl-1,2,4-triazole-3-thione showed a reversible inhibition of the competitive and non-competitive types, with Ki value of 10(-5) M magnitude, for α-glucosidase and α-amylase. On the other hand, 5-(o-hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thione did not display an inhibitory effect towards α-amylase but showed a potent inhibition of the competitive type for hepatic α-glucosidase with 10(-5) M magnitude of Ki value.
    European Journal of Medicinal Chemistry 06/2011; 46(6):2596-601. · 3.43 Impact Factor
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    ABSTRACT: Mutations in the genes encoding enzymes involved in the metabolism of chemical carcinogens can significantly affect the risk of cell transformation and cancer development. The resident Lebanese population has experienced a sharp increase in cancer incidence within the last few years. The relationship between gene polymorphisms of metabolic enzymes and gastrointestinal (GI) cancer incidence was not previously investigated. The aim of this study was to investigate the relationship between CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and GI cancer incidence among Lebanese. Blood and/or paraffin-embedded biopsy samples were collected from patients and healthy controls. The genotypes were determined by polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism. The results of the present case-control study show that the studied Lebanese population generally resembles Caucasian populations with respect to the considered polymorphisms. Further, the GSTM1*0/*0 genotype is a significant risk factor for gastric (odds ratio = 4.1; 95% confidence interval: 1.2-14.5) and colorectal cancers (odds ratio = 3.8; 95% confidence interval: 1.7-8.5); on the other hand, CYP1A1*2A and CYP2E1*6 alone are not significantly associated with GI cancer development, although CYP1A1*2A was more frequent among patients. A remarkable and statistically significant 36.5-fold increase in the risk of gastric cancer was observed among patients with CYP1A1*2A/*2A combined with GSTM1*0/*0. The investigation of genetic risk factors and susceptibility gene polymorphisms in Lebanese is helpful for better understanding of GI cancer etiology.
    Genetic Testing and Molecular Biomarkers 03/2011; 15(6):423-9. · 1.44 Impact Factor
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    ABSTRACT: Enzymes in mitochondria play an important role in biological oxidation and energy production. To understand the effect of schistosomiasis on these important processes, succinate cytochrome c reductase (SCR) from control and Schistosoma-infected mice was subjected for investigation. In this article, we report that SCR from Schistosoma-infected mouse showed a significant decrease in its Vmax and Km compared to control using both cytochrome c and 2,6-dichlorophenolindophenol as substrates. Furthermore, the kinetic studies of the purified SCR in the absence and presence of the schistosomicidal drugs praziquantel and Commiphora extract reveal that both drugs have an inhibitory action on the enzyme from the control and Schistosoma-infected mice and praziquantel changes the type of inhibition of SCR towards cytochrome c from mixed type in control to a competitive one in the case of the infection.
    Journal of physiology and biochemistry 12/2010; 66(4):291-9. · 1.65 Impact Factor
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    ABSTRACT: Quinazolinone derivatives have been studied as both in vitro and in vivo inhibitors of aspartate transcarbamylase (ATCase). In vitro treatment of mammalian ATCase with four compounds revealed that they inhibited enzyme activity and that 2-phenyl-1,3-4(H)benzothiazin-4-thione was the most potent one. This compound acts as a noncompetitive inhibitor towards both aspartate and carbamoyl phosphate. The values of the inhibition constant (K(i)) indicate that this compound exerts a potent inhibitory effect upon ATCase activity. Moreover, in vivo treatment with different doses of these derivatives showed also an inhibitory effect upon ATCase, the relative activity being decreased by 40%-58% with a 1 mg dose. These data support the inhibition of ATCase by quinazolinone derivatives as a new type of inhibitor for the enzyme.
    Journal of Enzyme Inhibition and Medicinal Chemistry 09/2008; 23(4):483-92. · 1.50 Impact Factor
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    Mahmoud Balbaa, Khaled Bassiouny
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    ABSTRACT: Arylsulfatase B (ASB) hydrolyzes the desulfation of N-acetylgalactosamine-4-sulfate at the non-reducing terminal of glycosaminoglycans. This enzyme activity was found to be elevated in mice schistosomiasis. In the present study, the catalytic and immunological properties of purified ASB from the liver of Schistosoma-infected mouse was investigated in the presence and absence of the schistosomicidal drugs praziquantel and Commiphora extract. The in vitro effect of praziquantel was found to be inhibitory with a Ki value of 5.5 x 10(-4) M while that of commiphora extract was as an activator. Furthermore, these drugs did not have an observed effect on the immunological properties of ASB with regard to its binding to its polyclonal rabbit antibody. These results indicate that some schistosomicidal drugs may reverse the alteration of the catalytic properties of the enzyme in schistosomiasis.
    Journal of Enzyme Inhibition and Medicinal Chemistry 03/2006; 21(1):81-5. · 1.50 Impact Factor
  • Mahmoud Balbaa, Jehan Al-Meer, Amina Al-Khal
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    ABSTRACT: Succinate-cytochrome c reductase was inhibited in vitro and in vivo by phenobarbitone, aminophylline and neostigmine using both 2,6-dichlorophenolindophenol (DCIP) and cytochrome c (cyt c) as substrates. The enzyme was also activated by gallamine towards both substrates. In vitro, phenobarbitone and aminophylline inhibited the enzyme with respect to the reduction of DCIP and cyt c in a non-competitive manner with Ki values of 1.5 x 10(-5) and 5.7 x 10(-5)M, respectively. Moreover, neostigmine competitively inhibited the enzyme towards both substrates with Ki values of 1.36 x 10(-5) and 1.50 x 10(-5)M, respectively.
    Journal of Enzyme Inhibition and Medicinal Chemistry 09/2004; 19(4):343-7. · 1.50 Impact Factor
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    ABSTRACT: The levels of arylsulfatases A and B, alpha-amylase, aspartate transcarbamylase, and gamma-glutamyl transpeptidase were investigated during the infection of mice with schistosoma mansoni. This infection caused a significant (p < 0.001) increase in the activity of hepatic arylsulfatase B (ASB), aspartate transcarbamylases and gamma-glutamyl transpeptidase. A non-significant difference occurred for alpha-amylase (p < 0.3) and arylsulfatase A (p > 0.5) when compared to the control. The specific activity of hepatic ASB was progressively increased with the progression of the Schistosoma-infection. Moreover, the kinetic studies of hepatic ASB in Schistosoma-infection showed that a slight decrease in the value of K(m) and about a 40% increase in V(max) when compared to the control. In addition, the pH optimum of hepatic ASB was altered from 6 to 7 as a result of schistosomiasis. These observations suggest that there are schistosomiasis-associated changes of the catalytic and kinetic properties of hepatic ASB.
    Journal of biochemistry and molecular biology 03/2004; 37(2):223-8. · 2.02 Impact Factor
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    ABSTRACT: The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-1-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on alpha- and beta-glucosidases, beta-glucuronidase as well as alpha-amylase have been investigated. alpha-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for alpha-glucosidase. Moreover, they exert a relatively potent inhibition on alpha-glucosidase with a Ki magnitude of 3.6 x 10(-4), 9.5 x 10(-5) M.
    Nucleosides Nucleotides &amp Nucleic Acids 11/2002; 21(10):695-708. · 0.71 Impact Factor
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    ABSTRACT: The in vivo and in vitro effects of 4-amino-3-(D-glucopentitol-l-yl)-5-mercapto-1,2,4-triazole and its 3-methyl analogue on α- and β-glucosidases, β-glucuronidase as well as α-amylase have been investigated. α-Glucosidase is the enzyme that is markedly affected in vivo and in vitro in a dose-dependent manner. The compounds showed a reversible inhibition of a competitive type for α-glucosidase. Moreover, they exert a relatively potent inhibition on α-glucosidase with a Ki magnitude of 3.6×10, 9.5×10 M.
    Nucleosides Nucleotides & Nucleic Acids - NUCLEOS NUCLEOT NUCLEIC ACIDS. 01/2002; 21(10):695-708.
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    ABSTRACT: Succinate-cytochrome c reductase (SCR) from mouse liver was inhibited strongly and reversibly by an iron (II) macrocyclic complex 3. The inhibition was observed for the enzyme toward the reduction of both 2,6-dichlorophenol indophenol (DCIP) and cytochrome c (cyt c). The inhibition was a mixed type and noncompetitive with respect to the reduction of DCIP and cyt c, respectively. Values of the inhibition constant ranged from 6.6 to 8.3 microM. The IC50 for the complex 3 was found to be 16.6 +/- 0.8 and 12.1 +/- 0.5 microM for the enzyme toward DCIP and cyt c, respectively. The reduced form of complex 3 also exhibited enzyme inhibition but to a less extent. Complex 3, at a lower level, equal to 25% of its LD50 showed about 50% inhibition of the enzyme through in vivo dose-dependent effect. These findings suggested that the structure of the equatorial benzoquinoid macrocyclic ligand of the Fe(II) complex is involved in the enzyme inhibition.
    Journal of enzyme inhibition 11/2001; 16(4):381-90.
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    ABSTRACT: Mammalian and hepatic aspartate transcarbamylase is inhibited by phenobarbital p-nitrophenylhydrazone in a reversible and non-competitive type with Ki values 8.45 x 10(-5) and 9.64 x 10(-5) M in the reactions toward carbamyl phosphate and aspartate, respectively. In vivo inhibition occurred in a dose-dependent manner in which less than 50% of the activity was retained. These observations suggest that this inhibitor may interfere with the in vivo regulation of this enzyme and lead to an additional biological effect of phenobarbitals.
    Journal of enzyme inhibition 02/2001; 16(3):259-67.
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    ABSTRACT: The hepatic lysosomal glycosidases α-glucosidase and β-glucuronidase were inhibited in vitro and in vivo by mono- and diethanolamines. The in vivo inhibition is dose dependent and occurs at a value less than LD50. Phenyl 6-deoxy-6-(morpholin-4-yl)-β-d-glucopyranoside inhibited α-glucosidase both in vitro and in vivo. The treatment of the enzymes in vitro by ethanolamine exhibited a reversible inhibition of the mixed and competitive types for α-glucosidase and β-glucuronidase, respectively. Diethanolamine showed a reversible inhibition of the competitive type for both enzymes. It is a potent inhibitor for β-glucuronidase, in vitro, whose inhibition constant (Ki) is 5×10−5 M. Phenyl 6-deoxy-6-(morpholin-4-yl)-β-d-glucopyranoside is a potent inhibitor only for hepatic α-glucosidase with a Ki value of 1.6×10−5 M. The pattern of the pH dependence of enzymic activity was not affected by ethanolamine inhibition. The magnitude of the inhibition of enzymes is dependent on the structure of the inhibitor.
    Carbohydrate Research 05/1999; 317:100-109. · 2.04 Impact Factor
  • Journal of Inorganic Biochemistry - J INORG BIOCHEM. 01/1997; 67(1):438-438.

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