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(3R, 3'R)-zeaxanthin protects the retina from photo-oxidative damage via modulating the inflammation and visual health molecular markers
(Taylor & Francis Ltd, 2019) Sahin, Kazim; Akdemir, Fatih; Orhan, Cemal; Tuzcu, Mehmet; Gencoglu, Hasan; Sahin, Nurhan; Ozercan, Ibrahim H.
Purpose: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan (R); OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. Methods: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration. Retinal morphology was analyzed by histopathology, and target gene expressions were detected with real-time polymerase chain reaction methods. Results: OMX treatment significantly increased the serum zeaxanthin concentration (p < 0.001) and ameliorated oxidative damage by increasing the antioxidant enzyme activities in the retina induced by light (p < 0.001). OMX administration significantly upregulated the expression of genes, including Rhodopsin (Rho), Rod arrestin (SAG), G alpha Transducin 1 (GNAT-1), neural cell adhesion molecule (NCAM), growth-associated protein 43 (GAP43), nuclear factor-(erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase (HO-1) and decreased the expression of nuclear factor-kappa B (NF- kappa B) and GFAP by OMX treatment rats. The histologic findings confirmed the antioxidant and gene expression data. Conclusions: This study suggests that OMX is a potent substance that can be used to protect photoreceptor cell degeneration in the retina exposed to intense light.
3R, 3?R zeaxanthin Protects Retina from Photo-Oxidative Damage: in vivo model
(Wiley, 2017) Sahin, Nurhan; Akdemir, Fatih; Orhan, Cemal; Tuzcu, Mehmet; Yilmaz, Ismet; Juturu, Vijaya
[Abstract Not Available]
Comparative evaluation of the sexual functions and NF-?B and Nrf2 pathways of some aphrodisiac herbal extracts in male rats
(Bmc, 2016) Sahin, Kazim; Orhan, Cemal; Akdemir, Fatih; Tuzcu, Mehmet; Gencoglu, Hasan; Sahin, Nurhan; Turk, Gaffari
Background: Mucuna pruriens, Tribulus terrestris and Ashwagandha (Withania somnifera) are widely known as antioxidant effective herbals and have been reported to possess aphrodisiac activities in traditional usages. In this study, we determined the effects of these herbals on sexual functions, serum biochemical parameters, oxidative stress and levels of NF-kappa B, Nrf2, and HO-1 in reproductive tissues. Methods: Thirty-five male rats were divided into five groups: the control group, sildenafil-treated group (5 mg/kg/d), Mucuna, Tribulus and Ashwagandha groups. The extract groups were treated orally either with Mucuna, Tribulus or Ashwagandha (300 mg/kg b.w.) for 8 weeks. Results: All of the extracts were found to be significantly effective in sexual functioning and antioxidant capacity and Tribulus showed the highest effectiveness. Serum testosterone levels significantly increased in Tribulus and Ashwagandha groups in comparison to control group. Tribulus was able to reduce the levels of NF-kappa B and increase the levels of Nrf2 and HO-1 to a much greater extent than Mucuna and Ashwagandha. Conclusions: These results demonstrate for the first time that Mucuna, Tribulus and Ashwagandha supplementation improves sexual function in male rats via activating Nrf(2)/HO-1 pathway while inhibiting the NF-kappa B levels. Moreover, Tribulus terrestris extract was found to be more bioavailable from Ashwagandha extract followed by Mucuna extract.
?-Cryptoxanthin ameliorates metabolic risk factors by regulating NF-?B and Nrf2 pathways in insulin resistance induced by high-fat diet in rodents
(Pergamon-Elsevier Science Ltd, 2017) Sahin, Kazim; Orhan, Cemal; Akdemir, Fatih; Tuzcu, Mehmet; Sahin, Nurhan; Yilmaz, Ismet; Juturu, Vijaya
The aim of this experiment was to determine the effects of beta-cryptoxanthin (BCX) on the cardiometabolic health risk factors and NF-kappa B and Nrf2 pathway in insulin resistance induced by high-fat diet (HFD) in rodents. Twenty-eight Sprague-Dawley rats were allocated into four groups: (1) Control, rats fed a standard diet for 12 weeks; (2) BCX, rats fed a standard diet and supplemented with BCX (2.5 mg/kg BW) for 12 weeks; (3) HFD, rats fed a HFD for 12 weeks, (4) HFD + BCX, rats fed a HFD and supplemented with BCX for 12 weeks. BCX reduced cardio-metabolic health markers and decreased inflammatory markers (P < 0.001). Rats fed a HFD had the lower total antioxidant capacity and antioxidant enzymes activities and higher MDA concentration than control rats (P < 0.001 for all). Comparing with the HFD group, BCX in combination with HFD inhibited liver NF-kappa B and TNF-alpha expression by 22% and 14% and enhanced liver Nrf2, HO-1, PPAR-alpha, and p-IRS-1 by 1.43,1.41, 3.53, and 1.33 fold, respectively (P < 0.001). Furthermore, in adipose tissue, BCX up-regulated Nrf2, HO-1, PPAR-alpha, and p-IRS-1 expression, whereas, down-regulated NF-kappa B and TNF-alpha expression. In conclusion, BCX decreased visceral fat and cardiometabolic health risk factors through modulating expressions of nuclear transcription factors. (C) 2017 Elsevier Ltd. All rights reserved.
Dietary Mango Ginger May Enhance the Exercise Performance and Reduces Lipid Profile when Combined with Treadmill Running in a Rat Model
(Wiley, 2017) Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Akdemir, Fatih; Pala, Ragip; Juturu, Vijaya
[Abstract Not Available]
The effect of dietary colostrum powder on performance, carcass yields and serum lipid peroxidation levels in Japanese quails (Coturnix coturnix japonica)
(Taylor & Francis Ltd, 2018) Akdemir, Fatih; Bayril, Tahir; Baran, Murat Sedat; Yildiz, Ahmet Sener; Kahraman, Mucahit; Orhan, Cemal; Sahin, Kazim
Colostrum is a nutrient-dense fluid secreted by female mammals for the first few days following birth. Colostrum can be supplemented to poultry diets as a feed additive due to its nutritious and performance-enhancing properties. This study was conducted to determine the effect of dietary colostrum powder (CL-P, Alpha Lipid Lifeline Colostrum, New Zealand) on growing performance, carcass weight and yield, organ weights, serum vitamins and malondialdehyde (MDA) levels in quails (Coturnix coturnix japonica). A total of 90 birds, one day old, were divided into 3 groups consisting of 6 replicate cages, 5 birds per cage. Birds were randomly fed on one of three diets: basal diet and basal diet supplemented with 2.5% or 5% of CL-P. At the end of the period of 42 days, CL-P supplementation increased final body weight (P < .0001), weight gain (P < .0001), feed intake (P = .03), feed efficiency (P < .0001), carcass weight (P < .0001) and carcass yield (P < .01). Amounts of serum MDA (P < .001) levels also increased with increasing supplemental CL-P. As a result, growth performance can be improved and serum lipid peroxidation can effectively be attenuated by dietary CL-P supplementation at 5% of diets in Japanese quail.
Effect of inositol -stabilized arginine silicate on arthritis in a rat model
(Pergamon-Elsevier Science Ltd, 2019) Sahin, Kazim; Ojalvo, Sara Perez; Akdemir, Fatih; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Ozercan, Ibrahim H.
The purpose of this study was to test the effects of arginine-silicate-inositol complex (ASI), compared to a combination of the individual ingredients (A + S + I) of the AM, on inflammatory markers and joint health in a collagen-induced arthritis (CIA) rat model. A total of 28 Wistar rats were divided into four groups: (i) Control; (ii) Arthritic group, rats subjected to CIA induction by injection of bovine collagen type II (A); (iii) Arthritic group treated with equivalent doses of the separate components of the ASI complex (arginine hydrochloride, silicon, and inositol) (A + S + I); (iv) Arthritic group treated with the ASI complex. The ASI complex treatment showed improved inflammation scores and markers over the arthritic control and the A + S + I group. ASI group had also greater levels of serum and joint-tissue arginine and silicon than the A + S + I group. Joint tissue IL-6, NF-kappa B, COX-2, TNF-alpha, p38 MAPK, WISP-1, and beta-Catenin levels were lower in the ASI group compared to the other groups (P < 0.05 for all). In conclusion, these results demonstrate that the ASI complex may be effective in reducing markers of inflammation associated with joint health and that the AM complex is more effective than a combination of the individual ingredients.
The effect of lycopene on antioxidant status in rainbow trout (Oncorhynchus mykiss) reared under high stocking density
(Elsevier Science Bv, 2014) Sahin, Kazim; Yazlak, Hasan; Orhan, Cemal; Tuzcu, Mehmet; Akdemir, Fatih; Sahin, Nurhan
Lycopene, the major carotenoid found in tomato, exhibits health beneficial effects by virtue of its antioxidant activity. As stocking density is known as a stress factor in fish, the effects of dietary lycopene supplementation (0, 200 or 400 mg kg(-1)) on growth performance and antioxidant status in rainbow trout under normal (20 kg m(3-1)) and high (100 kg m(3-1)) stocking density were studied. Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) activities were evaluated, as well as lipid peroxidation measured as malondialdehyde (MDA). Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), erythroid-derived 2-like 2 (Nrf2) and heme-oxygenase 1 (HO-1) levels were also assayed as an indicator of detoxifying/antioxidant defense mechanisms to cope with oxidative stress. Results showed that exposure to high stocking density depressed feed intake by 6.8% and body weight gain by 12.1%, increased plasma and hepatic MDA level by 88.5 and 124.3% and decreased hepatic SOD, CAT and GSH-Px activities by 22.1, 43.4 and 51.7%, respectively. In fish under crowded conditions, an expression of hepatic NF-kappa B was increased by 71.5%, being suppressed in Nrf2 and HO-1 by 40.6 and 42.7%, respectively. Lycopene supplementation increased linearly fish growth performance and antioxidant enzyme activity, and decreased linearly MDA concentration in both low and high stocking densities. NF-kappa B levels decreased hepatic Nrf2 and HO-1 levels increased linearly with lycopene supplementation at a greater extent in fish under low stocking condition. In conclusion, dietary supplementation of lycopene to fish reduces the detrimental effects of high stocking density on growth performance and modulates oxidative status via activating host defense system at cellular level. It appears that lycopene can be added up to 400 mg kg(-1) to rainbow trout diets to improve meat quality. (C) 2013 Elsevier B.V. All rights reserved.
The efficacy of dietary curcumin on growth performance, lipid peroxidation and hepatic transcription factors in rainbow trout Oncorhynchus Mykiss (Walbaum) reared under different stocking densities
(Wiley, 2017) Akdemir, Fatih; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Juturu, Vijaya; Sahin, Kazim
Curcumin, derived from Curcuma longa, exerts antioxidant, antibacterial, anticancer and immunomodulatory properties. This study was conducted to determine the effect of dietary water-soluble curcumin (0, 200 or 400mgkg(-1)) on growth performance and antioxidant status in rainbow trout (Oncorhynchus mykiss, Walbaum) rearing under normal (20kgm(-3)) or high (100kgm(-3)) stocking density conditions. A significant increase in body weight (FBW), feed intake (FI) and weight gain (BWG) was observed in fish fed with curcumin-supplemented diet at 200mgkg(-1) of diet levels of high stocking density conditions (P<0.0001), whereas feed conversion ratio (FCR) was not significant. Also, serum and liver malondialdehyde (MDA) levels were decreased by dietary curcumin in crowded fish (P<0.01, for both). With curcumin supplementation, expressions of heat shock protein 70 (HSP70; P<0.0001) and hepatic nuclear factor kappa-B (NF-B; P<0.01) decreased, whereas expressions of hepatic nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) (P<0.001, for both) increased in fish exposed to high stocking density. In conclusion, curcumin supplementation alleviates adverse effects of high stocking density on performance through modulating expressions of stress-related nuclear transcription factors in rainbow trout.
Lutein and Zeaxanthin isomers (L/Zi) Modulate Photo-Oxidative Retinal Damage in an Animal Model
(Assoc Research Vision Ophthalmology Inc, 2017) Juturu, Vijaya; Akdemir, Fatih; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Yilmaz, Ismet; Sahin, Kazim
[Abstract Not Available]
Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats
(Academic Press Inc Elsevier Science, 2019) Sahin, Kazim; Gencoglu, Hasan; Akdemir, Fatih; Orhan, Cemal; Tuzcu, Mehmet; Sahin, Nurhan; Yilmaz, Ismet
Background: Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. Methods: Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/8hD, 24hL/OhD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-kappa B), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. Results: L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IG1, Nrf2, and HO-1 levels. However, the levels of NF-kappa B and GFAP levels were decreased by administration of L/Zi. Conclusions: According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress. (C) 2019 Elsevier Inc. All rights reserved.
Lycopene improves activation of antioxidant system and Nrf2/HO-1 pathway of muscle in rainbow trout (Oncorhynchus mykiss) with different stocking densities
(Elsevier, 2014) Sahin, Kazim; Orhan, Cemal; Yazlak, Hasan; Tuzcu, Mehmet; Sahin, Nurhan
The purpose of this study was to describe the effect of lycopene on antioxidant status, heat shock protein 70 (Hsp70), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme-oxygenase 1(HO-1) levels in the muscle of rainbow trout (Oncorhynchus mykiss). The fish were kept at low(20 kg m(3 - 1)) or high(100 kg m(3 - 1)) stocking densities till the end of study and fed a basal diet or the basal diet supplemented with either 200 or 400 mg of lycopene kg(-1) of diet. The protein, lipid and ash contents in the muscle were not changed by the supplementation of lycopene in rainbow trout kept under high or low stocking densities. In response to increasing supplemental lycopene level, there were linear increases in lycopene levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities (P < 0.001) and Nrf2 and HO-1 levels of muscle; linear decreases in muscle malondialdehyde (MDA) and Hsp70 levels (P < 0.001). In conclusion, lycopene supplementation to fish reduces the detrimental effects of oxidative stress and lipid peroxidation resulting from stocking densities via activating host defence system at cellular level. (C) 2014 Elsevier B.V. All rights reserved.
MAT, a Novel Polyherbal Aphrodisiac Formulation, Enhances Sexual Function and Nrf2/HO-1 Pathway While Reducing Oxidative Damage in Male Rats
(Hindawi Ltd, 2018) Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Gencoglu, Hasan; Sahin, Nurhan; Akdemir, Fatih; Turk, Gaffari
Mucuna pruriens, Ashwagandha, and Tribulus terrestris are known as the enhancers for sexual health, functional activities, vitality, and longevity. These herbs had been widely used in the Ayurveda medicine as aphrodisiacs through the ages, and their efficacy was also verified separately in our previous publication. Therefore, the aim of this study was to determine the effects of Mucuna, Ashwagandha, and Tribulus complexes on sexual function in rats. Twenty-eight male rats allocated to four groups as follows: (i) negative control (C); (ii) positive control or sildenafil citrate treated group (5 mg/kg) (S); (iii) MAT1 (combination of 10 mg Mucuna (M) + 10 mg Ashwagandha (A) + 10 mg Tribulus (T)/kg BW); (iv) MAT 2 (20 mg Mucuna + 20 mg Ashwagandha + 20 mg Tribulus/kg BW). There was no significant difference found between the MAT1 and MAT2 groups while they showed significantly increased testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels when compared to the negative control. Significant increases in Nrf2/HO1 levels and decreases in NF-kappa B were detected in MAT groups similar to the decrease in serum and testis malondialdehyde (MDA) levels as compared to both controls. The spermmotility, count, and rate also significantly improved in both MAT groups, while ALT, AST, creatinine, ALP, and urea levels did not change in any of the groups. Oral consumption of MATs combination in male rats resulted in inhibition of NF-kappa B and MDA and also increased sex hormones with Nrf2-mediated HO-1 induction. MAT combinations may improve sexual functions by increasing levels of sexual hormones and regulation of NF-kappa B and Nrf2/HO-1 signaling pathways.
Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model
(Mary Ann Liebert, Inc, 2016) Orhan, Cemal; Akdemir, Fatih; Tuzcu, Mehmet; Sahin, Nurhan; Yilmaz, Ismet; Deshpande, Jayant; Juturu, Vijaya
Purpose: Mesozeaxanthin (MZ) is able to protect against chronic and cumulative eye damage and neutralize free radicals produced by oxidative stress. The objective of the present study was to evaluate the protective potential of MZ against retinal oxidative damage and growth and transcription factors of the retina in rats fed with high-fat diet (HFD). Methods: Twenty-eight Sprague Dawley rats were randomly divided into the following 4 groups: (1) Control, (2) MZ (100 mg/kg bw/d), (3) HFD (42% of calories as fat), and (4) HFD+MZ (100 mg/kg bw/d) group rats were administered daily as supplement for 12 weeks. Results: Consumption of HFD was associated with hyperglycemia and oxidative stress as reflected by increased serum MDA concentration (P < 0.001). No measurable zeaxanthin (Z)+MZ and lutein (L) could be detected in the serum of control and HFD rats, whereas they were observed in the serum of MZ-administered rats. Retinal antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities were significantly decreased in the HFD group compared to the normal group (P < 0.01). However, retinal antioxidant enzymes were restored close to normal levels in HFD+MZ-treated rats (P < 0.05). The retina of rats fed with HFD had increased levels of vascular endothelial growth factor (VEGF), inducible nitric oxide (iNOS), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor-kappa B (NF-kappa B) levels and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1(HO-1) levels compared to the healthy rat retina (P < 0.001). Rats treated with MZ partially alleviated the inflammation as reflected by suppressed VEGF, iNOS, ICAM, and NF-kB levels and increased Nrf2 and HO-1 levels in the retina of rats fed (P < 0.05). Conclusions: Results from the present study suggest that MZ has protective effects on the retina and the ability to modulate oxidative stress of retina in rats fed an HFD by suppressing retinal lipid peroxidation and regulating growth and transcription factors.
Mesozeaxanthin protects the liver and reduces cardio-metabolic risk factors in an insulin resistant rodent model
(Taylor & Francis Ltd, 2017) Sahin, Kazim; Orhan, Cemal; Akdemir, Fatih; Tuzcu, Mehmet; Sahin, Nurhan; Yilmaz, Ismet; Ali, Shakir
Background: Mesozeaxanthin (MZ) is a macular carotenoid which has been reported to have a number of pharmacological properties, including the antioxidant, and anticarcinogenic property, and has been stated to decrease the hepatocyte lipid content. Objective: In this study, we investigated the effect of MZ on cardio-metabolic health risk (CMHR) and its probable mechanisms of action in rats fed a high-fat diet (HFD). Design: Rats were randomly divided into four groups consisting of (i) Control, (ii) MZ, (iii) HFD, and (iv) HFD+MZ. Results: MZ treatment increased the antioxidant enzyme activities and helped improve the liver function. The treatment alleviated CMHR and decreased the level of nuclear factor kappa B (NF-kappa B p65) and tumor necrosis factor-alpha (TNF-alpha). The levels of hepatic peroxisome proliferator-activated receptor gamma (PPAR-gamma), phosphorylated insulin receptor substrate 1 (p-IRS-1), beta,beta-carotene 9', 10'-oxygenase 2 (BCO2) and nuclear factor erythroid 2-related factor 2 (Nrf2), which decrease in HFD rats, were found to be significantly higher in MZ supplemented animals. Conclusion: MZ has antioxidant and anti-inflammatory properties and can is reported in this study toprotect against fatty liver and cardio-metabolic syndrome, possibly through regulation of PPAR-gamma, IRS-1, Nrf2 and NF-kappa B proteins, in an insulin-resistant rodent model.
A Schiff base derivative for effective treatment of diethylnitrosamine induced liver cancer in vivo
(Anticancer Drugs, 2015) Demirci, Selami; Doğan, Ayşegül; Başak, Neşe; Dede, Bülent; Telci, Dilek; Orhan, Cemal; Tuzcu, Mehmet; Şahin, Kazım; Şahin, Nurhan; Özercan, İbrahim; Şahin, Fikrettin
Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-κB p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-κB (NF-κB p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.
A Schiff base derivative for effective treatment of diethylnitrosamine-induced liver cancer in vivo
(Lippincott Williams & Wilkins, 2015) Demirci, Selami; Dogan, Aysegul; Basak, Nese; Telci, Dilek; Dede, Bulent; Orhan, Cemal; Tuzcu, Mehmet
Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II) Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-kappa B p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-kappa B (NF-kappa B p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
Schiff base poloxamer P85 combination prevents prostate cancer progression in C57 Bl6 mice
(Prostate, 2016) Doğan, Ayşegül; Demirci, Selami; Başak, Neşe; Çağlayan, Ahmet Burak; Aydın, Safa; Telci, Dilek; Kılıç, Ertuğrul; Şahin, Kazım; Orhan, Cemal; Tuzcu, Mehmet; Şahin, Fikrettin; Doğan Ekinci, Işın Asiye
BACKGROUND. Prostate cancer which is the second most common cause of death among men has a high incidence in recent years. Current therapeutic regimens should be improved to overcome drug resistance. At the metastatic stage, tumors become refractory to established chemotherapeutic treatments and cause serious problems at the clinics. Development of new drug molecules that are able to transport through the membrane easily and kill tumor cells rapidly is of great interest. METHOD. In the current study, a novel Heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used for prostate cancer treatment in vivo. Tramp-C1 cells injected animals were subjected to chemotherapeutic formulation treatment and results were analyzed by toxicology analysis, tumor volume measurements, and histopathological analysis. 0.5 mg/kg Schiff base was selected and combined with 0.05% P85 according to the toxicology analysis showing the enzyme levels, blood parameters, and multiple organ toxicity. RESULTS. Results demonstrated that Heterodinuclear copper(II)Mn(II) complex-P85 combination decreased tumor formation and tumor volume steadily over the course of experiments. CONCLUSIONS. Overall, Heterodinuclear copper(II)Mn(II) complex-P85 exerted remarkable anti-cancer activity in vivo in C57/B16 mice. Prostate 76:1454–1463, 2016. # 2016 Wiley Periodicals, Inc.
Sıçanlarda, 7,12 Dimetil Benzantrasen ile Oluşturulan Yumuşak Doku Sarkomunda Genisteinin Koruyucu Rolü
(Fırat Üniversitesi Sağlık Bilimleri Veteriner Dergisi, 2018) Gençoğlu, Hasan; Tuzcu, Zeynep; Tuzcu, Mehmet; Orhan, Cemal; Akdemir, Fatih; Özercan, İbrahim H.; Şahin, Nurhan; Şahin, Kazım
Öz: Genistein, soya fasülyesinde bulunan biyolojik olarak en aktif izoflavondur. Genisteinin östrojenik, antiöstrojenik, anti kanserojenik ve immun regülatör özellikleri bilinmektedir. Bu çalışmada, genisteinin sıçanlarda kimyasal olarak oluşturulan yumuşak doku sarkomu üzerine etkileri araştırlmıştır. Bu amaçla, 45 adet Wistar albino ırkı erkek sıçan, her biri 15 hayvan içeren 3 deney grubuna rastgele ayrılmıştır. (i) Kontrol: Herhangi bir uygulama yapılmayan normal kontrol sıçanlarından oluştu. (ii) DMBA grubu: 7,12 dimetil benzantrasen (susam yağında çözülmüş DMBA, 50 mg/kg i.p.) ile fibroid tümör oluşturulan sıçanlardan oluştu. (iii) DMBA+Genistein grubu: Fibroid tümör oluşturulmak amacıyla DMBA’yı i.p. olarak ikinci gruba benzer şekilde alan ve 20 hafta boyunca genistein (400 mg/kg diyet) verilen sıçanlardan oluştu. Genistein takviyesi DMBA ile kıyaslandığında fibroid tümörlerin görülme sıklığını azalttı (P<0.01). Genistein ile beslenen sıçanlarda oluşan tümörler DMBA grubunda bulunanlardan daha küçüktü (P<0.001). Serum malondialdehit (MDA) (P<0.01), 8-izoprostan ve 4-hidroksialkenal (HAE) (P<0.05) düzeyleri genistein grubunda DMBA grubuna göre düşük bulundu. Gruplarda oksidatif hasarın bir göstergesi olan serum 8-OHdG konsantrasyonları, DMBA grubuna kıyasla DMBA+Genistein grubunda belirgin olarak azaldı (P<0.05). Bu sonuçlar, genistein takviyesinin sıçanlarda DMBA kaynaklı yumuşak doku sarkomlarının gelişimini inhibe edebildiğini göstermektedir.

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