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Antimutagenic efficacy of some natural compounds on cyclophosphamide-induced p53 alterations., Gouda, Eman M., El Behairy Adel M., and Ghoneim Magdy A. , Zeitschrift fur Naturforschung. C, Journal of biosciences, 2008 Nov-Dec, Volume 63, Issue 11-12, p.857-63, (2008) Abstract

Mutations in the p53 tumour suppressor gene have been associated with chemical carcinogens. Natural antimutagens are promising modulators for reducing the cancer risk. The present study was carried out to assess the protective efficacy of some natural antimutagens against p53 alterations. We investigated the ability of curcumin (100 mg/kg BW) and chlorophyllin (3 mg/kg BW) pretreatment, for three times per week for three successive weeks, to inhibit mutations induced by intraperitoneal injection of a single dose of 40 mg/kg BW of cyclophosphamide (CP). Forty male albino rats were assigned into four groups: control nontreated group, CP-treated group, curcumin-CP-treated group, and chlorophyllin-CP-treated group. Liver samples were collected for DNA isolation two days after CP injection. The isolated DNA was used in single-strand conformational polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified products of four regions: two in exon 5, one in exon 6, and one in exon 7. The amplified products of p53 different regions were found to be in the expected molecular size of the designed primers. SSCP analysis of these amplified products showed that CP-induced mutation in the p53 gene was found only in exon 7 shifting its electrophoretic mobility. Chlorophyllin treatment prior to CP injection had a more potent protective efficacy (80%) than that with curcumin (33.3%).

Conserved and non-conserved loci of the glucagon gene in old world ruminating ungulates., Warda, Mohamad, Gouda Eman M., El-Behairy Adel M., and Mousa Said Z. , Zeitschrift fur Naturforschung. C, Journal of biosciences, 2006 Jan-Feb, Volume 61, Issue 1-2, p.135-41, (2006) Abstract

The homology and diversification of genomic sequence encoding glucagon gene among native Egyptian buffalos, camel and sheep were tested using cattle as model. Oligodeoxynucleotide primers designed from the available GenBank data were used for PCR probing of the glucagon gene encoding sequence at different loci. The DNA oligomer probes were constructed to flank either the whole gene encoding sequence or different intra-gene encoding sequences. The PCR products were visualized using agarose gel electrophoresis. All species showed a same size band of prepro-glucagon when PCR was used to amplify the whole gene encoding sequence. In contrary, amplifications of different intra-gene loci failed to give the same results. The results indicated variable degrees of diversity among old world ruminating ungulates in the glucagon gene encoding sequence. Compared with other ruminants, the variation appears predominantly in camel. Surprisingly, the similarity in size between both amplification products of whole gene encoding sequence and the proposed size of glucagon cDNA definitely excludes the possibility of large intervening introns spanning the genomic sequence of the glucagon gene in these species. This indicates that, in contrast to other tested mammals, the glucagon gene includes an essentially full-length copy of glucagon mRNA. The study revealed a possible new aspect of glucagon gene evolution in order to correlate its corresponding protein function among different ruminant species.

Hepatocyte Growth Factor Mediates the Antifibrogenic Action of Ocimum bacilicum Essential Oil against CCl4-Induced Liver Fibrosis in Rats., Ogaly, Hanan A., Eltablawy Nadia A., El-Behairy Adel M., El-Hindi Hatim, and Abd-Elsalam Reham M. , Molecules (Basel, Switzerland), 2015 Jul 23, Volume 20, Issue 8, p.13518-35, (2015) Abstract

The current investigation aimed to evaluate the antifibrogenic potential of Ocimum basilicum essential oil (OBE) and further to explore some of its underlying mechanisms. Three groups of rats were used: group I (control), group II (CCl4 model) and group III (OBE-treated) received CCl4 and OBE 2 weeks after the start of CCl4 administration. Oxidative damage was assessed by the measurement of MDA, NO, SOD, CAT, GSH and total antioxidant capacity (TAC). Liver fibrosis was assessed histopathologically by Masson's trichrome staining and α-smooth muscle actin (α-SMA) immunostaining. Expression of hepatocyte growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real-time PCR and immunohistochemistry. OBE successfully attenuated liver injury, as shown by histopathology, decreased serum transaminases and improved oxidative status of the liver. Reduced collagen deposition and α-SMA immuopositive cells indicated an abrogation of hepatic stellate cell activation by OBE. Furthermore, OBE was highly effective in stimulating HGF mRNA and protein expression and inhibiting CCl4-induced CYP2E1 down-regulation. The mechanism of antifibrogenic action of OBE is hypothesized to proceed via scavenging free radicals and activating liver regeneration by induction of HGF. These data suggest the use of OBE as a complementary treatment in liver fibrosis.

Oxidative stress during erythropoietin hyporesponsiveness anemia at end stage renal disease: Molecular and biochemical studies., Khalil, Samar K. M., Amer H. A., El Behairy Adel M., and Warda Mohamad , Journal of advanced research, 2016 May, Volume 7, Issue 3, p.348-58, (2016) Abstract

Inflammation and oxidative stress are two faces of one coin in end stage renal disease patients (ESRD) on maintenance hemodialysis. Their interconnection induces anemia complicated with erythropoietin hyporesponsiveness. The biochemical bases behind the resistance to erythropoietin therapy with frequent hemoglobinemia, oxidative stress and iron status have not been fully understood. Here two equal groups (40 patients each) of responders and non-responders to recombinant human erythropoietin therapy (higher than 300 IU/kg/wk of epoetin) were investigated. Hematological and biochemical analyses of collected blood and serum samples were performed along with serum electrophoretic protein footprinting. The leukocytic DNA fragmentation was used to evaluate the degree of oxidative insult. The good responders showed lower erythrocyte malondialdehyde (E-MDA) level and less DNA fragmentation of circulating leukocytes than poor responders with elevated hemoglobin, albumin, A/G ratio, total iron, and ferritin levels. Contrariwise, lower erythrocyte superoxide dismutase (E-SOD) and catalase activities in EPO poor responder group were noticed. Neither other serum constituents nor electrophoretic protein pattern showed any difference between the two groups. There were higher levels of inflammatory markers, interleukin-6 (IL6) and C-reactive protein (CRP) in EPO poor responder than good responder. The negative correlations between Hb and both IL6 and CRP levels in the present data remotely indicate a positive correlation between inflammatory markers and severity of anemia. A direct correlation between Hb and antioxidant enzymes (E-SOD and catalase) was noticed, while inverse correlation with E-MDA was recorded. The study proved that oral supplementation of vitamin C to ESRD patients might mitigate the previously elevated serum MDA level in these patients.

Protective effect of curcumin and chlorophyllin against DNA mutation induced by cyclophosphamide or benzo[a]pyrene., Marwa A Ibrahim, El Behairy Adel M., Ghoneim Magdy A., and Amer Hassan A. , Zeitschrift fur Naturforschung. C, Journal of biosciences, 2007 Mar-Apr, Volume 62, Issue 3-4, p.215-22, (2007) Abstract

The current study was carried out to evaluate the potency of curcumin and chlorophyllin as natural antioxidants to reduce the oxidative stress markers induced by cyclophosphamide (CP) and benzo[a]pyrene [B(a)P] which were used as free radical inducers. For this purpose, 126 male albino rats were used. The animals were assigned into 4 main groups: negative control group; oxidant-treated group (subdivided into two subgroups: cyclophosphamide-treated group and benzo[a]pyrene-treated group); curcumin-treated group; and chlorophyllin-treated group. Liver samples were collected after two days post the oxidant inoculation and at the end of the experimental period (10 weeks). These samples were examined for determination of liver microsomal malondialdehyde (MDA), DNA fragmentation, restriction fragment length polymorphism (RFLP) and 8-hydroxy deoxyguanosine (8-OHdG) concentration. Both CP and B(a)P caused increments in DNA fragmentation percentages, liver microsomal MDA, concentration of 8-OHdG and induced point mutation. Treatment of rats with either curcumin or chlorophyllin revealed lower DNA fragmentation percentages, liver microsomal MDA concentration, concentration of 8-OHdG and prevented induction of mutations, i.e., reversed the oxidative stress induced by CP and B(a)P and proved that they were capable of protecting rats against the oxidative damage evoked by these oxidants.

Reproductive toxic impact of subchronic treatment with combined butylparaben and triclosan in weanling male rats., Riad, Madeha A., Abd-Rabo Marwa M., Abd El Aziz Samy A., El Behairy Adel M., and Badawy Mohamed M. , Journal of biochemical and molecular toxicology, 2018 Jan 19, (2018) Abstract

The effect of treatment with combined butylparaben and triclosan on male gonadal toxicity in weanling rats was investigated. All treated groups experienced atrophy in the ventral prostate and seminal vesicle, likewise significant depletion in the number and motility of sperm. Given individually or combined butylparaben and triclosan, significantly decreased testosterone, luteinizing hormone, and follicle-stimulating hormone levels. Individual treatment with tested compounds caused significant elevation in the Elevel, whereas combined treatment did not alter the Elevel. Testicular DNA damage was recorded in all treated groups. Moreover, the testicular malondialdehyde level was significantly elevated, along with a significant decrease in catalase enzyme activity in all treated groups. Superoxide dismutase enzyme activity was significantly decreased in the butylparaben-treated group, increased in the triclosan-treated group, and nonsignificantly changed the butylparaben-triclosan-treated group. The combined treatment produced an endocrine disturbance with a concomitant induction of testicular oxidative stress, which may represent a common mechanism of endocrine disruptor-mediated dysfunction.