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Scopus (1 → 3)-β-d-glucan enhances the toxicity induced by Bortezomib in rat testis(2020-03-01) Akaras N.; Abuc O.O.; Koc K.; Bal T.; Geyikoglu F.; Atilay H.; Erol H.S.; Yigit S.; Gul M.We aimed to determine the possible effects of the antioxidant agent (1 → 3)-β-D-glucan on bortezomib-induced rat testis damage. We used five groups of rats; control, (1 → 3)-β-D-glucan (75 mg/kg), bortezomib group, bortezomib + (1 → 3)-β-D-glucan groups (injection of (1 → 3)-β-D-glucan after bortezomib and sacrificed at 48th or 72nd h). The effects of these substances were assessed by measuring the levels of the antioxidant enzymes and LPO, and by performing immunohistochemical analysis with NF-κB. The histology of testis was evaluated using aniline blue staining. (1 → 3)-β-D-glucan leads to significant reductions in the levels of antioxidant enzymes and increased levels of LPO in testes. Moreover, it increased the NF-κB immunopositivity significantly in testis, especially in Bortezomib + (1 → 3)-β-D-glucan group at 48th h. The histological changes were observed in the bortezomib and/or (1 → 3)-β-D-glucan groups. Our results demonstrated that testis damage caused by the treatment with bortezomib was not eliminated by (1 → 3)-β-D-glucan and shockingly it increased the damage. Practical applications: The testis damage caused by the treatment with bortezomib was not eliminated by (1 → 3)-β-D-glucan and as a result, β-1,3-(D)-glucan enhanced the toxicity by leading a decrease in the levels of GSH, SOD, and CAT, thus caused an elevation in the immunoreactivity of NF-κB and altered the histopathological changes by enhancing the toxic effects of bortezomib. The findings of the previous studies about the antioxidative activity of (1 → 3)-β-D-glucan are controversial. So, it is necessary to consider the cytotoxicity of (1 → 3)-β-D-glucan in testis tissue. Thus, more studies on testis tissue are necessary to confirm that (1 → 3)-β-D-glucan is safe as an antioxidant.Publication (1 → 3)-β-d-glucan enhances the toxicity induced by Bortezomib in rat testis.(2020-03-01T00:00:00Z) Akaras, Nurhan, Abuc, Ozlem Ozgul, Koc, Kubra, Bal, Tugba, Geyikoglu, Fatime, Atilay, Hilal, Erol, Huseyin Serkan, Yigit, Serdar, Gul, Murat; Akaras, N, Abuc, OO, Koc, K, Bal, T, Geyikoglu, F, Atilay, H, Erol, HS, Yigit, S, Gul, MWe aimed to determine the possible effects of the antioxidant agent (1 → 3)-β-D-glucan on bortezomib-induced rat testis damage. We used five groups of rats; control, (1 → 3)-β-D-glucan (75 mg/kg), bortezomib group, bortezomib + (1 → 3)-β-D-glucan groups (injection of (1 → 3)-β-D-glucan after bortezomib and sacrificed at 48th or 72nd h). The effects of these substances were assessed by measuring the levels of the antioxidant enzymes and LPO, and by performing immunohistochemical analysis with NF-κB. The histology of testis was evaluated using aniline blue staining. (1 → 3)-β-D-glucan leads to significant reductions in the levels of antioxidant enzymes and increased levels of LPO in testes. Moreover, it increased the NF-κB immunopositivity significantly in testis, especially in Bortezomib + (1 → 3)-β-D-glucan group at 48th h. The histological changes were observed in the bortezomib and/or (1 → 3)-β-D-glucan groups. Our results demonstrated that testis damage caused by the treatment with bortezomib was not eliminated by (1 → 3)-β-D-glucan and shockingly it increased the damage. PRACTICAL APPLICATIONS: The testis damage caused by the treatment with bortezomib was not eliminated by (1 → 3)-β-D-glucan and as a result, β-1,3-(D)-glucan enhanced the toxicity by leading a decrease in the levels of GSH, SOD, and CAT, thus caused an elevation in the immunoreactivity of NF-κB and altered the histopathological changes by enhancing the toxic effects of bortezomib. The findings of the previous studies about the antioxidative activity of (1 → 3)-β-D-glucan are controversial. So, it is necessary to consider the cytotoxicity of (1 → 3)-β-D-glucan in testis tissue. Thus, more studies on testis tissue are necessary to confirm that (1 → 3)-β-D-glucan is safe as an antioxidant.Publication 1-[4-(4-Chlorophenyl)piperazin-1-yl]-3-(6-oxo-3,4-diphenyl-1, 6-dihydropyridazin-1-yl)propan-1-one(2012-09-01) Aydn A., Akkurt M., Doǧruer D.S., Büyükgüngör O.; Aydin, A, Akkurt, M, Dogruer, DS, Buyukgungor, OIn the title compound, C29H27ClN4O 2, the six-membered ring of the pyridazine group is nearly planar [maximum deviation = -0.062 (2) Å] and its mean plane makes dihedral angles of 43.05 (9), 44.71 (10) and 72.57 (9)°, respectively, with the two phenyl and benzene rings. The piperazine ring has a chair conformation and its mean plane is almost perpendicular to the attached benzene ring, with a dihedral angle of 83.20 (16)°. In the crystal, molecules are linked via two pairs of C - H⋯O interactions, which result in the formation of chains propagating along [101̄]. Neighbouring chains are linked via C - H⋯π interactions.Scopus 1-[4-(4-Chlorophenyl)piperazin-1-yl]-3-(6-oxo-3,4-diphenyl-1, 6-dihydropyridazin-1-yl)propan-1-one(2012-09-01) Aydn A.; Akkurt M.; Doǧruer D.S.; Büyükgüngör O.In the title compound, C29H27ClN4O 2, the six-membered ring of the pyridazine group is nearly planar [maximum deviation = -0.062 (2) Å] and its mean plane makes dihedral angles of 43.05 (9), 44.71 (10) and 72.57 (9)°, respectively, with the two phenyl and benzene rings. The piperazine ring has a chair conformation and its mean plane is almost perpendicular to the attached benzene ring, with a dihedral angle of 83.20 (16)°. In the crystal, molecules are linked via two pairs of C - H⋯O interactions, which result in the formation of chains propagating along [101̄]. Neighbouring chains are linked via C - H⋯π interactions.Publication 2-(6-Benzoyl-2-oxo-1,3-benzothiazol-3-yl)acetic acid(2010-01-22) Aydn A., Akkurt M., Önkol T., Büyükgüngör O., Şahin M.F.; Aydin, A, Akkurt, M, Onkol, T, Buyukgungor, O, Sahin, MFIn the title compound, C16H11NO4S, the nine-membered fused ring is nearly planar, with maximum deviations from the mean plane of-0.022 (1) Å for the N atom and 0.011 (1) Å for the S atom, and makes a dihedral angle of 53.56 (7)° with the phenyl ring. The crystal structure is stabilized by O-H⋯O and C-H⋯O hydrogen-bonding inter-actions.Scopus 2-(6-Benzoyl-2-oxo-1,3-benzothiazol-3-yl)acetic acid(2010-01-22) Aydn A.; Akkurt M.; Önkol T.; Büyükgüngör O.; Şahin M.F.In the title compound, C16H11NO4S, the nine-membered fused ring is nearly planar, with maximum deviations from the mean plane of-0.022 (1) Å for the N atom and 0.011 (1) Å for the S atom, and makes a dihedral angle of 53.56 (7)° with the phenyl ring. The crystal structure is stabilized by O-H⋯O and C-H⋯O hydrogen-bonding inter-actions.Scopus 2-[2-(4-Benzyl-piperazin-1-ylcarbon-yl)eth-yl]-5,6-diphenyl-pyridazin-3(2H) -one(2008-12-12) Aydn A.; Doruer D.S.; Akkurt M.; Büyükgüngör O.The title compound, C30H30N4O2, has a non-planar conformation, the dihedral angles formed by the pyridazinone ring plane and the three phenyl rings being 54.61 (7), 51.10 (7) and 59.53 (8)°. The piperazine ring adopts a chair conformation. Inter- and intra-molecular C - H⋯O contacts are found in the crystal structure and these consolidate the three-dimensional packing.Publication 2-[2-(4-Benzyl-piperazin-1-ylcarbon-yl)eth-yl]-5,6-diphenyl-pyridazin-3(2H) -one(2008-12-12) Aydn A., Doruer D.S., Akkurt M., Büyükgüngör O.; Aydin, A, Dogruer, DS, Akkurt, M, Buyukgungor, OThe title compound, C30H30N4O2, has a non-planar conformation, the dihedral angles formed by the pyridazinone ring plane and the three phenyl rings being 54.61 (7), 51.10 (7) and 59.53 (8)°. The piperazine ring adopts a chair conformation. Inter- and intra-molecular C - H⋯O contacts are found in the crystal structure and these consolidate the three-dimensional packing.Scopus 2-{2-[4-(4-Fluoro-phenyl)piperazin-1-yl]-2-oxoethyl}-6-(morpholin-4-yl) -4-phenyl-pyridazin-3(2H)-one(2011-03-01) Aydin A.; Şüküroǧlu M.; Akkurt M.; Büyükgüngör O.In the title compound, C26H28FN5O 3, the morpholine ring adopts a chair conformation. The piperazine ring is puckered [QT = 0.5437 (15) Å, θ = 8.89 (15) and φ = 357.2 (11)°]. The 1,6-dihydropyridazine ring makes dihedral angles of 28.03 (7) and 77.46 (7)° with the phenyl and benzene rings, respectively. In the crystal, molecules are linked along the c axis by C - H⋯O interactions and are flattened parallel to the ac plane. C - H⋯π interactions also contribute to the stability of the structure.Publication 2-{2-[4-(4-Fluoro-phenyl)piperazin-1-yl]-2-oxoethyl}-6-(morpholin-4-yl) -4-phenyl-pyridazin-3(2H)-one(2011-03-01) Aydin A., Şüküroǧlu M., Akkurt M., Büyükgüngör O.; Aydin, A, Sukuroglu, M, Akkurt, M, Buyukgungor, OIn the title compound, C26H28FN5O 3, the morpholine ring adopts a chair conformation. The piperazine ring is puckered [QT = 0.5437 (15) Å, θ = 8.89 (15) and φ = 357.2 (11)°]. The 1,6-dihydropyridazine ring makes dihedral angles of 28.03 (7) and 77.46 (7)° with the phenyl and benzene rings, respectively. In the crystal, molecules are linked along the c axis by C - H⋯O interactions and are flattened parallel to the ac plane. C - H⋯π interactions also contribute to the stability of the structure.Scopus 3-(4-Chloro-benzo-yl)-4-(4-chloro-phen-yl)-1-phenethyl-piperidin-4-ol(2011-06-01) Aydin A.; Akkurt M.; Mete E.; Sahin E.; Gul H.In the title compound, C26H25Cl2NO 2, the piperidine ring adopts a chair conformation with a cis configuration of the carbonyl and hy-droxy substituents. The dihedral angle between the aromatic rings of the chloro-benzene groups is 24.3 (2)°. The phenyl ring forms dihedral angles of 59.4 (3) and 44.1 (3)° with the benzene rings. In the crystal, mol-ecules are linked by inter-molecular O - H⋯N and C - H⋯O hydrogen bonds and C - H⋯π inter-actions into layers parallel to the bc plane.Publication 3-(4-Chloro-benzo-yl)-4-(4-chloro-phen-yl)-1-phenethyl-piperidin-4-ol(2011-06-01) Aydin A., Akkurt M., Mete E., Sahin E., Gul H.; Aydin, A, Akkurt, M, Mete, E, Sahin, E, Gul, HIIn the title compound, C26H25Cl2NO 2, the piperidine ring adopts a chair conformation with a cis configuration of the carbonyl and hy-droxy substituents. The dihedral angle between the aromatic rings of the chloro-benzene groups is 24.3 (2)°. The phenyl ring forms dihedral angles of 59.4 (3) and 44.1 (3)° with the benzene rings. In the crystal, mol-ecules are linked by inter-molecular O - H⋯N and C - H⋯O hydrogen bonds and C - H⋯π inter-actions into layers parallel to the bc plane.Publication 3-({4-[(2-Methyl-benzyl-idene)amino]-5-sulfanyl-idene-1H-1,2,4-triazol-3-yl}meth-yl)-1,3-benzoxazol-2(3H)-one.(2013-02-01T00:00:00Z) Aydın, Abdullah, Hekimoğlu, Nuray, Akkurt, Mehmet, Onkol, Tijen, Ciçekli, Sölen Urlu, Büyükgüngör, OrhanIn the title compound, C(18)H(15)N(5)O(2)S, a weak intra-molecular C-H⋯S hydrogen bond results in a small dihedral angle of 3.71 (9)° between the methyl-phenyl and triazole rings, which, in turn, form dihedral angles of 80.09 (8) and 77.32 (8)°, respectively, with the benzoxazolone mean plane. In the crystal, N-H⋯O hydrogen bonds link mol-ecules into chains along [001], and weak C-H⋯N hydrogen bonds and π-π inter-actions between the five- and six-membered rings [centroid-centroid distances = 3.5074 (11) and 3.616 (1) Å] consolidate the crystal packing.Scopus 3-({4-[(2-Methylbenzylidene)amino]-5-sulfanylidene-1H-1,2,4-triazol-3-yl} methyl)-1,3-benzoxazol-2(3H)-one(2013-02-01) Aydn A.; Hekimoǧlu N.; Akkurt M.; Önkol T.; Çiçekli S.U.; Büyükgüngör O.In the title compound, C18H15N5O2S, a weak intramolecular C - H⋯S hydrogen bond results in a small dihedral angle of 3.71 (9)° between the methylphenyl and triazole rings, which, in turn, form dihedral angles of 80.09 (8) and 77.32 (8)°, respectively, with the benzoxazolone mean plane. In the crystal, N - H⋯O hydrogen bonds link molecules into chains along [001], and weak C - H⋯N hydrogen bonds and π-π interactions between the five- and six-membered rings [centroid-centroid distances = 3.5074 (11) and 3.616 (1) Å] consolidate the crystal packing.Publication 3-Anilinomethyl-5-chloro-1,3 - Benzoxazol-2(3H)-one(2012-05-01) Aydin A., Soyer Z., Akkurt M., Büyükgüngör O.; Aydin, A, Soyer, Z, Akkurt, M, Buyukgungor, OIn the title compound, C14H11ClN2O 2, the 2,3-dihydro-1,3-benzoxazole ring system is essentially planar [maximum deviation = 0.009 (2) Å] and makes a dihedral angle of 79.15 (7)°with the phenyl ring. Inter-molecular N - H⋯O and weak C - H⋯Cl hydrogen bonds occur in the crystal structure. © Aydn et al. 2012.Scopus 3-Anilinomethyl-5-chloro-1,3 - Benzoxazol-2(3H)-one(2012-05-01) Aydin A.; Soyer Z.; Akkurt M.; Büyükgüngör O.In the title compound, C14H11ClN2O 2, the 2,3-dihydro-1,3-benzoxazole ring system is essentially planar [maximum deviation = 0.009 (2) Å] and makes a dihedral angle of 79.15 (7)°with the phenyl ring. Inter-molecular N - H⋯O and weak C - H⋯Cl hydrogen bonds occur in the crystal structure. © Aydn et al. 2012.Scopus 4-[(2E)-2-(4-Chlorobenzylidene)hydrazinylidene]-1-methyl-1, 4-dihydro-pyridine monohydrate(2010-06-11) Aydn A.; Akkurt M.; Alptüzün V.; Büyükgüngör O.; Holzgrabe U.; Radacki K.In the title compound, C13H12ClN3· H2O, the organic mol-ecule is almost planar, with a dihedral angle of 3.22 (10)° between the benzene and pyridine rings. The crystal structure is stabilized by O - H⋯N and C - H⋯O hydrogen bonding and π-π stacking inter-actions [centroid-centroid distances = 3.630 (1) and 3.701 (1) Å].Publication 4-[(2E)-2-(4-Chlorobenzylidene)hydrazinylidene]-1-methyl-1, 4-dihydro-pyridine monohydrate(2010-06-11) Aydn A., Akkurt M., Alptüzün V., Büyükgüngör O., Holzgrabe U., Radacki K.; Aydin, A, Akkurt, M, Alptuzun, V, Buyukgungor, O, Holzgrabe, U, Radacki, KIn the title compound, C13H12ClN3· H2O, the organic mol-ecule is almost planar, with a dihedral angle of 3.22 (10)° between the benzene and pyridine rings. The crystal structure is stabilized by O - H⋯N and C - H⋯O hydrogen bonding and π-π stacking inter-actions [centroid-centroid distances = 3.630 (1) and 3.701 (1) Å].Scopus A cardioprotective role of Nerium oleander with the expression of hypoxia inducible factor 2A mRNA by increasing antioxidant enzymes in rat heart tissue(2018-01-01) Hitit M.; Corum O.; Corum D.D.; Donmez H.; Cetin G.; Dik B.; Er A.Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes. Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene. The expression of manganese superoxide dismutase (MnSOD) mRNA was in a steady state level between the control group and group 2 (P > 0.05); however, it significantly increased in group 3 and 4 compared with that in the control (P < 0.05). Expression of catalase (CAT) mRNA was significantly higher in group 2 than in the control group (P < 0.05) although it was lower in group 3 and 4 than in group 2 (P < 0.05); however, it appeared to be similar among the control group, group 3, and group 4 (P > 0.05). Copper (Cu) SOD mRNA was equally expressed in both the control group and group 2 (P > 0.05) but was lower in group 3 and 4 than in group 2 (P < 0.05). Expressions of HIF1A, HIF2A, and HIF3A mRNA were detected in the rat heart tissues in the control and 2, 4, and 8 h after administration of NO distillate. Expression of HIF1A mRNA was in a steady state and did not differ among groups 2, 3, and 4 (P > 0.05). Similarly, the expression of HIF2A mRNA did not change between the control group and group 2 (P > 0.05); however, it was higher in group 3 than in the control (P < 0.05) and tended to be higher in group 3 than in group 2 (P = 0.063). HIF3A mRNA expression did not change significantly in the heart tissue of any of the groups (P > 0.05). Discussion: The present study using rats determined that MnSOD, CAT, CuSOD, HIF1A, HIF2A, and HIF3A mRNA are expressed in the heart tissues after administration of NO distillate. The increased expression of HIF2A mRNA after 4 h in accordance with a rise in CAT mRNA after 2 h, and MnSOD mRNA after 4 and 8 h might confirm the role of HIF2A mRNA in oxidative stress defense by regulating antioxidant enzymes; consequently, this study may expand our understanding of uses of NO distillate with respect to molecular pathways.Publication A cardioprotective role of Nerium oleander with the expression of hypoxia inducible factor 2A mRNA by increasing antioxidant enzymes in rat heart tissue(2018-01-01) Hitit M., Corum O., Corum D.D., Donmez H., Cetin G., Dik B., Er A.; Hitit, M, Corum, O, Corum, DD, Donmez, H, Cetin, G, Dik, B, Er, ABackground: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes. Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene. The expression of manganese superoxide dismutase (MnSOD) mRNA was in a steady state level between the control group and group 2 (P > 0.05); however, it significantly increased in group 3 and 4 compared with that in the control (P < 0.05). Expression of catalase (CAT) mRNA was significantly higher in group 2 than in the control group (P < 0.05) although it was lower in group 3 and 4 than in group 2 (P < 0.05); however, it appeared to be similar among the control group, group 3, and group 4 (P > 0.05). Copper (Cu) SOD mRNA was equally expressed in both the control group and group 2 (P > 0.05) but was lower in group 3 and 4 than in group 2 (P < 0.05). Expressions of HIF1A, HIF2A, and HIF3A mRNA were detected in the rat heart tissues in the control and 2, 4, and 8 h after administration of NO distillate. Expression of HIF1A mRNA was in a steady state and did not differ among groups 2, 3, and 4 (P > 0.05). Similarly, the expression of HIF2A mRNA did not change between the control group and group 2 (P > 0.05); however, it was higher in group 3 than in the control (P < 0.05) and tended to be higher in group 3 than in group 2 (P = 0.063). HIF3A mRNA expression did not change significantly in the heart tissue of any of the groups (P > 0.05). Discussion: The present study using rats determined that MnSOD, CAT, CuSOD, HIF1A, HIF2A, and HIF3A mRNA are expressed in the heart tissues after administration of NO distillate. The increased expression of HIF2A mRNA after 4 h in accordance with a rise in CAT mRNA after 2 h, and MnSOD mRNA after 4 and 8 h might confirm the role of HIF2A mRNA in oxidative stress defense by regulating antioxidant enzymes; consequently, this study may expand our understanding of uses of NO distillate with respect to molecular pathways.