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10.1371/journal.pone.0184157

http://scihub22266oqcxt.onion/10.1371/journal.pone.0184157
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suck abstract from ncbi


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pmid28892514      PLoS+One 2017 ; 12 (9): ä
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  • L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization #MMPMID28892514
  • El-Hamoly T; El-Sharawy DM; El Refaye MS; Abd El-Rahman SS
  • PLoS One 2017[]; 12 (9): ä PMID28892514show ga
  • 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 (1?g/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.
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