Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-104 |
Sentence |
denotes |
Chloroacetaldehyde as a sulfhydryl reagent: the role of critical thiol groups in ifosfamide nephropathy. |
T2 |
105-269 |
Sentence |
denotes |
Chloroacetaldehyde (CAA) is a metabolite of the alkylating agent ifosfamide (IFO) and putatively responsible for renal damage following anti-tumor therapy with IFO. |
T3 |
270-371 |
Sentence |
denotes |
Depletion of sulfhydryl (SH) groups has been reported from cell culture, animal and clinical studies. |
T4 |
372-479 |
Sentence |
denotes |
In this work the effect of CAA on human proximal tubule cells in primary culture (hRPTEC) was investigated. |
T5 |
480-608 |
Sentence |
denotes |
Toxicity of CAA was determined by protein content, cell number, LDH release, trypan blue exclusion assay and caspase-3 activity. |
T6 |
609-659 |
Sentence |
denotes |
Free thiols were measured by the method of Ellman. |
T7 |
660-784 |
Sentence |
denotes |
CAA reduced hRPTEC cell number and protein, induced a loss in free intracellular thiols and an increase in necrosis markers. |
T8 |
785-876 |
Sentence |
denotes |
CAA but not acrolein inhibited the cysteine proteases caspase-3, caspase-8 and cathepsin B. |
T9 |
877-930 |
Sentence |
denotes |
Caspase activation by cisplatin was inhibited by CAA. |
T10 |
931-1055 |
Sentence |
denotes |
In cells stained with fluorescent dyes targeting lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. |
T11 |
1056-1153 |
Sentence |
denotes |
The effects of CAA on cysteine protease activities and thiols could be reproduced in cell lysate. |
T12 |
1154-1343 |
Sentence |
denotes |
Acidification, which slowed the reaction of CAA with thiol donors, could also attenuate effects of CAA on necrosis markers, thiol depletion and cysteine protease inhibition in living cells. |
T13 |
1344-1449 |
Sentence |
denotes |
Thus, CAA directly reacts with cellular protein and non-protein thiols, mediating its toxicity on hRPTEC. |
T14 |
1450-1494 |
Sentence |
denotes |
This effect can be reduced by acidification. |
T15 |
1495-1586 |
Sentence |
denotes |
Therefore, urinary acidification could be an option to prevent IFO nephropathy in patients. |