Thyroid hormones are well-established as a key regulator of many cellular metabolic pathways developed in various pathogeneses. Here, we dedicated the current work to investigate the role of thyroid hormone analogue (L-thyroxine, L-TH) in regulating the renal cytotoxicity using in vivo and in vitro models. Swiss mice were exposed to gamma radiation (IRR, 6Gy) or treated with cisplatin (CIS, 15 mg/kg, i.p.) for induction of nephrotoxicity. Remarkably, pretreatment with L-TH (1μg/kg) ameliorated the elevated kidney function biomarkers, oxidative stress and protected the renal tissue from the subsequent cellular damage. Likewise, L-TH inhibited the apoptotic cascade by down-regulating the extreme consumption of the cellular energy (ATP), the expression of caspase-3 and Bax, and the stimulation of cyclic ADP ribose (cADPR)/calcium mobilization. Moreover, incubation with L-TH (120nM/4h) significantly blocked the cytotoxicity of CIS on Vero cells and the depletion of NAD+ content as well as modified the ADP-ribose cyclase (CD38) enzymatic activity. High doses of L-TH (up to30 nM/4h) inversely increased the radiosensitivity of Vero cells towards IRR (up to 6Gy). On the other hand, L-TH did not interfere CIS-induced cytotoxicity of colorectal adenocarcinoma (Caco-2) cell line. In conclusion, pretreatment with L-TH could be a promising protective approach to the renal cellular damage induced during either CIS or IRR therapy by regulating the unbalanced oxidative status, the expression of pro-apoptotic biomarkers via modulation of cADPR mediated-calcium mobilization.
N UCLEAR medicine is one the most important fields to inspect and treat tumors by radiation or by introducing labeled radiopharmaceuticals, which are in the spot of our interest. In this study, the authors investigated the possibility of using mebeverine as a solid tumor marker. Mebeverine was labeled with Technetium ( 99m Tc-Meb) reaching a radiochemical yield (RCY) of 97% via a reduction reaction using SnCl 2 . The tracer showed a high stability in the serum for 12 hours which is essential to avoid any undesired accumulations in the non-target organs. Its bioevaluation in normal and induced tumored mice was performed to identify the capability of the use of the tracer for the diagnosis of solid tumors. The uptake by the tumor was 14.2% after 30 min of injection and increased to 18.5%, viewing a decline after 3 hours, this could be attributed to that washout to the tumored muscle extravasation. Tumored /Non-Tumored (T/ NT) ratio was applied, the ratio reached 3.14 which shows the selectivity of 99m Tc-Meb to the solid tumor induced in the right thigh.
The objective of this study is to label Amoxicillin with radioactive iodine (125I-AC) via direct electrophilic substitution to act as a promising tracer for inflammation imaging. The highest labeling yield of 80% was achieved after studying all the parameters affecting the labeling reaction using Iodogen (IG) as an oxidizing agent. Molecular Modeling Structure was done using MOE program to predict the suitable 125I position. The product structure was established by a cold iodination reaction using Iodine-127. Biological evaluation of (125I-AC) was carried out using groups of inflamed mice with different exogenous agents such as E.Coli and Turpentine oil. The (125I-AC) shows an in vitro stability of about 97% after 24 h.While doing in vivo studies over 4 h, the tracer stability of 99% was observed.
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