Tayem, YIY;
(2006)
The role of haem oxygenase-1 modulation by isothiocyanates in drug-induced renal failure.
Doctoral thesis , UCL (University College London).
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Abstract
The effect of two isothiocyanates (ITCs), S-(N-benzylthiocarbamoyl)-L-cysteine (BTCC) and S-(N-3-phenylpropylthiocarbamoyl)-L-cysteine (PTCC), in modulating the haem oxygenase-1 (HO-1) pathway was investigated in order to identify a possible strategy for protecting renal cells and tissue against drug-induced toxicity. HO-1 is a versatile inducible enzyme that provides cytoprotection by generating the signalling molecule carbon monoxide (CO) and the antioxidant couple biliverdin (BV) and bilirubin (BR). When cultured renal tubular epithelial (LLC-PK1) cells were exposed to BTCC and PTCC, an increase in HO-1 expression and activity was observed in a time- and concentration-dependent manner. This effect required activation of MAPKs, PKC and PI-3K signal transduction pathways. Interestingly, both BTCC and PTCC caused apoptosis in LLC-PK1 cells when used at concentrations above 20 uM but rendered these cells resistant to apoptotic cell death when low concentrations (5 and 10 uM) were used. In fact, pre-incubation of LLC-PK1 cells with 5 or 10 uM BTCC or PTCC conferred major resistance to apoptosis mediated by cisplatin (CP), an effective anti-neoplastic agent known to cause nephrotoxicity by damaging proximal tubular cells.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | The role of haem oxygenase-1 modulation by isothiocyanates in drug-induced renal failure |
| Identifier: | PQ ETD:593192 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1445868 |
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