Effects of Curcumin on Iron Overload in Rats

Background: Iron overload, common in patients with hematological disorders, is a key target in drug development. This study investigated the effects of curcumin on iron overload in rats. Methods: Forty male Wistar rats weighing 139.78 ± 11.95 gm (Mean ± SD) were divided into three equal groups: (i) controls; (ii) iron overload group that received six doses of iron dextran 1000 mg/kg–1 by intraperitoneal injections (i.p.); and (iii) iron overload curcumin group that received six doses of curcumin (1000 mg/kg BW by i.p.).  In addition to six doses of iron dextran 1000 mg/kg–1 by i.p., we studied the effects of curcumin on liver function enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]); antioxidant enzymes (malondialdehyde [MDA], total oxidant status [TOS], total antioxidant status [TAS]); hematological parameters (hemoglobin [Hb], hematocrit [Hct], red blood cells [RBC], white blood cells [WBC], mean corpus volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC]); and iron parameters (serum iron profile, transferrin, total iron-binding capacity [TIBC], ferritin, and transferrin saturation [TS%]). Results: Curcumin caused a significant decrease in the Hct and Hb concentrations in Group III (P < 0.05). It also significantly reduced the serum levels of ALT (52.45 ± 4.51 vs 89.58 ± 4.65 U/L) and AST (148.03 ± 6.47 vs 265.27 ± 13.02 U/L) at the end of the study (P < 0.05). The TIBC, transferrin levels, and TS significantly decreased when the rats were administered curcumin serum iron (P < 0.05). The TAS level significantly increased in Group III in comparison to Group I (the control group) (P < 0.05). At the end of the study, curcumin significantly reduced the serum levels of TOS (12.03 ± 2.8 vs 16.95 ± 5.05 mmol H2O2/L) while the TAS (1.98 ± 0.42 vs 1.06 ± 0.33 mmol Trolox equiv./L) was increased. Conclusion: The findings of the present study suggest the therapeutic potential of curcumin against iron overload

The effects of daylight exposure on melatonin levels, Kiss1 expression, and melanoma formation in mice

Aim To determine how daylight exposure in mice affects melatonin protein expression in blood and Kiss1 gene expression in the hypothalamus. The second aim was to assess the relationship between skin cancer formation, daylight exposure, melatonin blood level, and kisspeptin gene expression level. Methods New-born mice (n = 96) were assigned into the blind group or daylight group. The blind group was raised in the dark and the daylight group was raised under 12 hours light/12 hours dark cycle for 17 weeks. At the end of the 11th week, melanoma cell line was inoculated to mice, and tumor growth was observed for 6 weeks. At the end of the experiment, melatonin level was measured from blood serum and Kiss1 expression from the hypothalamus. Results The blind group had significantly higher melatonin and lower Kiss1 expression levels than the daylight group. Tumor volume was inversely proportional to melatonin levels and directly proportional to Kiss1 expression levels. Tumor growth speed was lower in the blind than in the daylight group. Conclusion Melatonin and Kiss1 were shown to be nvolved in tumor suppression. They were affected by daylight and were mutually affected by each other

Kurkumin demir (III) kompleksinin demir şelasyonunun in vitro etkileri

Purpose: The aim of this study was to investigate the cytotoxicity effect, iron chelator and antioxidant activities of iron (III) ions with curcumin ligand that may be used in the treatment of iron overload. Materials and Methods: The cytotoxic activities of the ligand and the complex were evaluated by the MTT assay. The SOD activity of the complex of curcumin was determined by using its ability to inhibit the reduction of NBT. The catalytic activity studies of Fe(III) complex in DMSO towards the disproportionation of hydrogen peroxide were also performed. Results: The IC50 values are found in 6.8 μM catalase activity was measured. Where at a concentration of 2.0 mM, the activity was equivalent to 183.30 U/L. The complex shows a catalase activity. The complex showed minimal toxicity. IC50 values found 5.3 mg/ml. The observed cytotoxicity could be pursued to obtain a potential drug. The iron chelator effects were determined by Ferrozine reagent. Curcumin, the most active extract interfered with the formation of ferrous and ferrozine complex. It demonstrated strong chelating activities. The result showed that the complexes possess considerable SOD activity. This finding indicates that the iron complex is capable of removing free radicals. Conclusion: The study results revealed that the iron(III) complex of curcumin with an appropriate potential drug may act as a protector against oxidative stress. Therefore, all results suggest that curcumin may represent a new approach in the treatment of iron overload.Amaç: Bu çalışmanın amacı, aşırı demir yüklenmesinin tedavisinde kullanılması muhtemel olan kurkumin ligandı ve demir(III) iyonlarının sitotoksik etkisini, demir şelatörünü ve antioksidan etkinliğini araştırmaktır. Gereç ve Yöntem: Ligandın ve kompleksin sitotoksik etkileri MTT yöntemi kullanılarak değerlendirildi. Kurkumin kompleksinin SOD etkinliği, kompleksin NBT azaltımını inhibe etme kabiliyetine göre belirlendi. Buna ilaveten, demir(III) kompleksinin DMSO’daki hidrojen peroksitin disproporsiyonu reaksiyonuna yönelik katalitik etkinliği de çalışıldı. Bulgular: IC50 değerleri, 6.8 μM katalaz etkinliğinde ölçüldü. Konsantrasyonun 2.0 mM, olduğu durumda etkinlik seviyesi 183.30 U/L olarak ölçüldü. Kompleksin katalaz etkinliği gösterdiği ve minimal seviyede toksisiteye sebep olduğu görüldü. IC50 değerlerinin, 5.3 mg/ml’ye denk geldiği görüldü. Gözlenen sitotoksisitenin takip edilmesiyle, potansiyel bir ilacın elde edilmesinin muhtemel olduğu görüldü. Demir şelatörün etkileri Ferrozin reaktif bileşiği ile belirlendi. Demir ve Ferrozine kompleksinin oluşmasına müdahale eden en aktif ekstraktın kurkumin olduğu görüldü. Ayrıca, kurkuminin güçlü şelasyon etkinliğine sahip olduğu görüldü. Elde edilen bulgular bu komplekslerin önemli derecede SOD etkinliğine sahip oldukları görüldü. Dolaysıyla bu bulgular demir kompleksinin serbest radikalleri yok etme gücüne sahip olduğuna işaret etmektedirler. Sonuç: Bu çalışmada elde edilen bulgular, uygun bir potansiyel ilaç ile beraber kullanıldığında demir(III) kurkumin kompleksinin oksidatif strese karşı bir koruyucu olarak işlev görebileceğini göstermektedir. Dolayısıyla elde edilen bütün bulgular, kurkuminin aşırı demir yüklenmesinin tedavisinde yeni bir yaklaşım olabileceğine işaret etmektedirler

Investigation of muscarinic receptors in mesenchymal stem cells obatined from different sources in vitro and influence of receptor blockadge on differentiation.

TEZ12441Tez (Doktora) -- Çukurova Üniversitesi, Adana, 2016.Kaynakça (s. 76-84) var.xiv, 85 s. :_res. (gnl. rnk.), tablo ;_29 cm.Hücreler birbirleri ile endojen maddeler ve reseptörleri aracılığı ile iletişim kurarak fonksiyonel aktivitelerini yerine getirirler. Rejenerasyon amacıyla nakli yapılan kök hücrelerin de yerleştikleri yeni dokuda dokunun gerektirdiği fonksiyonel aktiviteleri göstermeleri uygun reseptörleri hücre yüzeylerinde taşımaları ile mümkün olabilir. Mezenkimal kök hücrelerde hangi reseptörlerin bulunduğunun gösterilmesi bu hücrelerin rejenerasyon amacıyla daha uygun kullanılmasını sağlayacaktır. Bu çalışmada insan plasenta fetal membranı (FM) ve kemik iliğinden (Kİ) elde edilen MKH'lerde, 1., 2. ve 3. pasajda, osteojenik, adipojenik farklılaşmada, ek olarak atropin etkisindeki farklılaşmada, muskarinik reseptörlerin M1, M2, M3, M4, M5alt gruplarının mRNA ekspresyon düzeyleri RT-qPCR ile gösterildi. Blokörlerin farklılaşmaya etkisinin tespit edilmesi amacıyla osteojenik açıdan Bone Morphogenetic Protein (BMP-6) ve Peroxisome Proliferator-Activated Receptor Gamma (PPAR?), adipojenik açıdan PPAR? mRNA ekspresyonları da RT-qPCR ile araştırıldı. Çalışmamızda, kontrol grubuna göre, M1 mRNA ekspresyonunda FM gruplarında genel olarak anlamlı bir artış saptandı. Farklı olarak bu durum Kİ grupları için azalma yönünde görüldü. M5 mRNA ekspresyonu yönünden kontrole göre FM gruplarında anlamlı değişiklikler bulunmadı fakat aynı reseptörün Kİ gruplarında anlamlı azalma yönünden sonuçlar elde edildi. Osteojenik farklılaşmış hücrelerde FM ve Kİ gruplarında BMP-6 mRNA ekspresyonları, farklılaşmamış hücrelere göre anlamlı derecede artış gösterdi fakat, atropin etkisinde osteojenik farklılaşan hücrelerde, normal osteojenik farklılaşmış gruba göre BMP-6 mRNA ekspresyonlarında anlamlı fark saptanmadı. Her iki kaynaktan elde edilen gruplarda adipojenik farklılaşmış hücrelerde PPAR? mRNA ekspresyonlarında kontrol grubuna göre anlamlı artışlar tespit edidi. Farklı olarak FM grubunda atropin etkisinde farklılaşan hücre grubu, normal adipojenik farklılaşan gruba göre ekspresyonda anlamlı olmasa da artış gösterirken, Kİ için bu durum azalma yönünde saptandı. Bu sonuçlar muskarinik reseptörlerin ekspresyonları yönünden farklı kaynaklardan elde edilen hücrelerin farklı davrandıklarını ve aynı kaynaktan olan hücrelerde de pasaj ve farklılaşmalara göre değişiklikler olduğunu göstermektedir. Bu nedenle klinik amaçlı kullanılan bu hücrelerin daha etkili kullanılmaları için farklı kaynaklardan ve aynı kaynaktan farklı pasajlardan elde edilerek in-vivo çalışmalarla muskarinik reseptör ve diğer reseptörler açısından araştırılmaları önem göstermektedir.Cells carry out their functional activity by communicating via endogenous substances and receptors with each other. The stem cells also transplanted so as to regeneration settled into the new tissue, to show the functional activities as required of the tissuemay be able to transport the receptors on their surface of the cells. To show thatwhichreceptors reside in themesenchymalstem cellswill be providedtouseof more convenient of the cells so as to regeneration. In this study, human placenta, fatal membrane (FM) and bone marrow (BM)derived MSCs in the1st, 2 ndand 3 rdpassage, osteogenic andadipogenicdifferentation,additively, in the differentiation under the effect of atropine, Mrna expression levels M1, M2, M3, M4 and M5 subtypes of muscarinic receptorswereshown by RT-qPCR. So as todetermination of the blockers the effects on differentiation from osteogenic aspectBoneMorphogenetic Protein (BMP-6) andPeroxisomeproliferator-Activated Receptor gamma (PPAR) were investigatedfromadipogenicaspectPPAR?, mRNA expressions were investigated via RT-qPCR. In our study, compared to the control groups, generally determined significantly increase on M1 mRNA expressions of FM groups. M5 mRNA expression compared to control group did notchanged significantly but in the KI groups of the samereceptorshowedsignificantly decreased. BMP-6 mRNA expressions in the FM and KI groupsof osteogenicdifferentiatedcells showedincrease significantly compare to undifferentiated cells, but did not determined significantly change theBMP-6 mRNA expressionstheeffect of atropine in the osteogenicdifferentiated cells compared to normal osteogenic differentiated cells. In the groups derived from both sourcesPPAR?mRNA expressions inadipogenicdifferentiatedcellsshowed the significant increase compared to control group. Distinctly, whereas the cell group of the atropine effect in the FM groupincreasednonsignificantlycompared to normaladipogenicdifferentiatedcells, it decreased this expressionsignificantly. This results indicatethe cells obtained from the different sources in that the expressions of muscarinic receptors behave disparately and indicate that there are also some changes derived from the same sources cells according to the passage and differentiation. Therefore, thiscellsused so as to clinical purposeto use moreeffective obtaining from the different sources and from the different passages in the same sourcedemonstratetheimportance to investigate in terms of muscarinicreceptorsand the other receptors with in vivo studies.Bu çalışma Ç.Ü. Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Proje No: TF2014D2

Kurkumin demir(III) kompleksinin demir şelasyonunun in vitro etkileri

Purpose: The aim of this study was to investigate the cytotoxicity effect, iron chelator and antioxidant activities of iron (III) ions with curcumin ligand that may be used in the treatment of iron overload. Materials and Methods: The cytotoxic activities of the ligand and the complex were evaluated by the MTT assay. The SOD activity of the complex of curcumin was determined by using its ability to inhibit the reduction of NBT. The catalytic activity studies of Fe(III) complex in DMSO towards the disproportionation of hydrogen peroxide were also performed. Results: The IC50 values are found in 6.8 μM catalase activity was measured. Where at a concentration of 2.0 mM, the activity was equivalent to 183.30 U/L. The complex shows a catalase activity. The complex showed minimal toxicity. IC50 values found 5.3 mg/ml. The observed cytotoxicity could be pursued to obtain a potential drug. The iron chelator effects were determined by Ferrozine reagent. Curcumin, the most active extract interfered with the formation of ferrous and ferrozine complex. It demonstrated strong chelating activities. The result showed that the complexes possess considerable SOD activity. This finding indicates that the iron complex is capable of removing free radicals. Conclusion: The study results revealed that the iron(III) complex of curcumin with an appropriate potential drug may act as a protector against oxidative stress. Therefore, all results suggest that curcumin may represent a new approach in the treatment of iron overload.Amaç: Bu çalışmanın amacı, aşırı demir yüklenmesinin tedavisinde kullanılması muhtemel olan kurkumin ligandı ve demir(III) iyonlarının sitotoksik etkisini, demir şelatörünü ve antioksidan etkinliğini araştırmaktır. Gereç ve Yöntem: Ligandın ve kompleksin sitotoksik etkileri MTT yöntemi kullanılarak değerlendirildi. Kurkumin kompleksinin SOD etkinliği, kompleksin NBT azaltımını inhibe etme kabiliyetine göre belirlendi. Buna ilaveten, demir(III) kompleksinin DMSO’daki hidrojen peroksitin disproporsiyonu reaksiyonuna yönelik katalitik etkinliği de çalışıldı. Bulgular: IC50 değerleri, 6.8 μM katalaz etkinliğinde ölçüldü. Konsantrasyonun 2.0 mM, olduğu durumda etkinlik seviyesi 183.30 U/L olarak ölçüldü. Kompleksin katalaz etkinliği gösterdiği ve minimal seviyede toksisiteye sebep olduğu görüldü. IC50 değerlerinin, 5.3 mg/ml’ye denk geldiği görüldü. Gözlenen sitotoksisitenin takip edilmesiyle, potansiyel bir ilacın elde edilmesinin muhtemel olduğu görüldü. Demir şelatörün etkileri Ferrozin reaktif bileşiği ile belirlendi. Demir ve Ferrozine kompleksinin oluşmasına müdahale eden en aktif ekstraktın kurkumin olduğu görüldü. Ayrıca, kurkuminin güçlü şelasyon etkinliğine sahip olduğu görüldü. Elde edilen bulgular bu komplekslerin önemli derecede SOD etkinliğine sahip oldukları görüldü. Dolaysıyla bu bulgular demir kompleksinin serbest radikalleri yok etme gücüne sahip olduğuna işaret etmektedirler. Sonuç: Bu çalışmada elde edilen bulgular, uygun bir potansiyel ilaç ile beraber kullanıldığında demir(III) kurkumin kompleksinin oksidatif strese karşı bir koruyucu olarak işlev görebileceğini göstermektedir. Dolayısıyla elde edilen bütün bulgular, kurkuminin aşırı demir yüklenmesinin tedavisinde yeni bir yaklaşım olabileceğine işaret etmektedirler

Effects of curcumin on iron overload in rats

Background: Iron overload, common in patients with hematological disorders, is a key target in drug development. This study investigated the effects of curcumin on iron overload in rats.Methods: Forty male Wistar rats weighing 139.78 ± 11.95 gm (Mean ± SD) were divided into three equal groups: (i) controls; (ii) iron overload group that received six doses of iron dextran 1000 mg/kg−−1 by intraperitoneal injections (i.p.); and (iii) iron overload curcumin group that received six doses of curcumin (1000 mg/kg BW by i.p.). In addition to six doses of iron dextran 1000 mg/kg−−1 by i.p., we studied the effects of curcumin on liver function enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]); antioxidant enzymes (malondialdehyde [MDA], total oxidant status [TOS], total antioxidant status [TAS]); hematological parameters (hemoglobin [Hb], hematocrit [Hct], red blood cells [RBC], white blood cells [WBC], mean corpus volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC]); and iron parameters (serum iron profile, transferrin, total iron-binding capacity [TIBC], ferritin, and transferrin saturation [TS%]).Results: Curcumin caused a significant decrease in the Hct and Hb concentrations in Group III (P < 0.05). It also significantly reduced the serum levels of ALT (52.45 ± 4.51 vs 89.58 ± 4.65 U/L) and AST (148.03 ± 6.47 vs 265.27 ± 13.02 U/L) at the end of the study (P < 0.05). The TIBC, transferrin levels, and TS significantly decreased when the rats were administered curcumin serum iron (P < 0.05). The TAS level significantly increased in Group III in comparison to Group I (the control group) (P < 0.05). At the end of the study, curcumin significantly reduced the serum levels of TOS (12.03 ± 2.8 vs 16.95 ± 5.05 mmol H2O2/L) while the TAS (1.98 ± 0.42 vs 1.06 ± 0.33 mmol Trolox equiv./L) was increased.Conclusion: The findings of the present study suggest the therapeutic potential of curcumin against iron overload

Biological behaviors of muscarinic receptors in mesenchymal stem cells derived from human placenta and bone marrow

WOS: 000498871600017Objective(s): Cells perform their functional activities by communicating with each other through endogenous substances and receptors. Post-translation, stem cells function properly in new host tissue by carrying specific cell surface receptors. We aimed to characterize muscarinic receptor subtypes in mesenchymal stem cells (MSCs) together with osteogenic and adipogenic differentiation markers. Materials and Methods: mRNA levels of 5 muscarinic receptor subtypes (CHRM1 to 5), BMP-6, and PPAR gamma during osteogenic and adipogenic differentiation, under the effect of atropine blockade, were measured in MSCs obtained from human fetal membrane (FM) and bone marrow (BM). Additionally, the effect of atropine on differentiation in the 1st, 2nd, and 3rd passages of MSCs, obtained from human FM and BM, were analyzed by RT-qPCR. Results: CHRM1 mRNA levels increased in the FM group, while decreasing in the BM group. We found significant decreases in CHRM3 and CHRM5 mRNA levels in FM and BM groups, respectively. Atropine had variable effects based on cell source and receptor type. BMP-6 mRNA levels in differentiated osteogenic cells increased significantly compared to undifferentiated cells in both FM and BM groups. In MSCs derived from both sources, PPAR gamma mRNA levels in differentiated adipogenic cells increased significantly. Atropine showed no effect on MSCs differentiation. Conclusion: These results indicate that expressions of muscarinic receptors in MSCs derived from BM and FM can vary and these cells keep the potential of osteogenic and adipogenic differentiation in vitro. Besides, atropine had no effect on adipogenic and osteogenic differentiation of MSCs.Cukurova University, Scientific Research Projects Fund, Adana, Turkey [TF2014D2]The results presented in this paper were part of a student thesis. The authors express their great gratitude to Canan Cansun and Nilay Oktar for their invaluable help in the RT-qPCR technique. This study was supported by Cukurova University, Scientific Research Projects Fund, Adana, Turkey (project no: TF2014D2)

Dipyrone ameliorates behavioural changes induced by unpredictable chronic mild stress: gender differences

Purpose: Antidepressant effects of analgesics have been investigate in both clinical and experimental studies. The purpose of this study was to investigate if the analgesic-antipyretic drug, dipyrone, also had antidepressant-like effects. Methods: Depression-like effects were investigated in an unpredictable chronic mild stress (UCMS) model in both male and female mice. Cage changes, light-dark cycle reversal, cage tilting, wet floor, empty cage, foreign material on the floor and predator sounds were used to induce light stress at different times for six weeks. Dipyrone was administered intraperitoneally beginning from the third week. Splash, rota-rod (RR) and forced swimming (FST) tests were performed at the seventh week as behavioural tests to evaluate the antidepressant-like effects of dipyrone. Coat state score (CSS) and weights of animals were recorded at seventh weeks. Results were analyzed using one or two-way ANOVA followed by the Bonferonni post hoc test. Results: Weight of UCMS-exposed mice did not change compared with controls; however, significant changes were observed in CSS in both sexes of stressed mice (