In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats

WOS: 000243214100044PubMed ID: 17387769Radiotherapy is one of the most common therapies for treating human cancers. Several studies have indicated that irradiation induces reactive oxygen species (ROS), which play an important role in radiation damage of the cell. It has been shown that Nigella sativa L. (NS) and reduced glutathione (GSH) have both an antiperoxidative effect on different tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant and radioprotective roles of INS and GSH against irradiation-induced oxidative injury in an experimental model. The INS group was administrated INS (1 mL/kg body weight), the GSH group was injected GSH (150 mg/kg body weight) and the control group was given physiologic saline solution (1 mL/kg body weight) for 30 consecutive days before exposure to a single dose of 6 Gy of radiation. Animals were sacrificed after irradiation. Malondialdehyde, nitrate, nitrite (oxidative stress markers) and ascorbic acid, retinol, beta-carotene, GSH and ceruloplasmin (nonenzymatic antioxidant markers) levels and peripheral blood lymphocytes were measured in all groups. There were statistically significant differences between the groups for all parameters (P < 0.05). Whole-body irradiation caused a significant increase in blood malondial-dehyde, nitrate and nitrite levels. The blood oxidative stress marker levels in irradiated rats that were pretreated with NS and GSH were significantly decreased; however, nonenzymatic antioxidant levels were significantly increased. Also, our results suggest that NS and GSH administration prior to irradiation prevent the number of alpha-naphthyl acetate esterase peripheral blood T lymphocytes from declining. These results clearly show that NS and GSH treatment significantly antagonize the effects of radiation. Therefore, NS and GSH may be a beneficial agent in protection against ionizing radiation-related tissue injury

Synthesis and biodistribution studies of two novel radiolabeled estrone derivatives

WOS: 000253841300016PubMed ID: 18396789Background: Two Tc-99m-DTPA attached estrone derivatives were synthesized and their radiopharmaceutical potential was determined using female albino Wistar rats. Materials and Methods: Two novel radiolabeled estrone derivatives, Tc-99m-2,2',2 '',2'''-(2,2-(2-(3-methoxy-13-methyl-17-oxo- 7, 8, 9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-diyl))bis(azanettiyl) tetraacetic acid (Tc-99m-2-DTPA-3-methoxy estrone) and Tc-99m-2,2',2 '',2'''-(2,2'-(2-(3-methoxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-4-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-dlyl))bis(azanettiyl)tetraacetic acid (Tc-99m-4DTPA-3-methoxy estrone) were synthesized starting from estrone (3-hydroxy-13-methyl-7,8, 9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one) and DTPA anhydride (2-(bis(2-(2,6-dioxomorpholino)ethyl)amino)acetic acid) as potential estrogen receptor imaging agents. The products were crystallized in ethyl alcohol (95%), purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). The effect of the radiolabeled compounds on the biological behaviour of the molecules was evaluated through biodistribution studies in female albino Wistar rats. The rats were sacrificed at various time intervals, their organs were removed, and the activities of organs were counted using a gamma counter equipped with a Cd(Te) solid state detector. Results and Conclusion: Organ uptake was calculated as activity/gram tissue and time versus activity curves were generated. The tissue distribution studies exhibited a receptor-mediated uptake in the target organs of the rats for each compound. Both Tc-99m-2-DTPA-3-methoxy estrone and (99m)Tc4-DTPA-3-methoxy estrone were stable in vitro and were mainly excreted through the hepatobiliary pathway.. The biological data showed that the Tc-99m-2-DTPA-3-methoxy estrone had higher uptake in the target tissues than the Tc-99m-4-DTPA-3-methoxy estrone. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical applications

Synthesis of a Novel Antiestrogen Radioligand (Tc-99m-TOR-DTPA)

WOS: 000272955600009PubMed ID: 20025551This study was aimed at developing a hydrophilic radioligand as an antiestrogen drug derivative to be used for imaging breast tumors. Toremifene [TOR; 4-chloro-1,2-diphenyl-1-(4-(2-(N,N-di-methylamino)ethoxy)phenyl)-1-butene, as citrate salt] was selected as the starting material to be derived, since it has been used extensively as an antiestrogen drug for treatment and prevention of human breast cancer. An antiestrogen drug derivative, TOR attached to diethylenetriamine pentaacetic acid (DTPA), was synthesized by two experimental treatments, including a purification and a reaction step. We described the synthesis of this TOR derivative, (3Z)-4-{4-[2-(dimethylamino) ethoxy] phenyl}-3,4-diphenylbut-3-en-1-ylN,N-bis[2-(2,6-dioxomorpholin-4-yl)ethyl]glycinate (TOR-DTPA), in detail. Mass spectroscopy confirmed the expected structures. TOR-DTPA was labeled with technetium-99m (Tc-99m), using stannous chloride (SnCl2) as the reducing agent. Biodistribution studies were performed on female Albino Wistar rats. Quality controls, radiochemical yield, and stability studies were done utilizing high-performance liquid chromatography, radioelectrophoresis, thin-layer chromatography, and thin-layer radiochromatography methods. The synthesized compound was found to be hydrophilic and anionic, with high stability for the duration of the testing period in vitro. The results indicated that the radiolabeled compound has estrogen-receptor specificity, especially for the breast tissue. It is highly possible that this compound could be used for imaging breast tumors as a novel technetium-labeled hydrophilic estrogen derivative radioligand.Turkish Prime Ministry, State Planning Organization [06 DPT 06]; Ege University Research FundEge University [2007 NBE 006]This work was funded by the Turkish Prime Ministry, State Planning Organization (contact no. 06 DPT 06) and Ege University Research Fund (contact no. 2007 NBE 006, Izmir, Turkey). The authors thank Prof. Dr. Feza Ozturk for editing the English language. The authors also thank Prof. Dr. Tamerkan Ozgen and research assistant, Murat Erdogan, for GS/MS/MS measurements in the Izmir Institute of Technology, Department of Chemistry