Romano, Giulia
(2008)
Contrast agents and renal cell apoptosis.
[Tesi di dottorato]
(Unpublished)
| Item Type: |
Tesi di dottorato
|
| Lingua: |
English |
| Title: |
Contrast agents and renal cell apoptosis |
| Creators: |
| Creators | Email |
|---|
| Romano, Giulia | romanogiul@yahoo.it |
|
| Date: |
11 December 2008 |
| Number of Pages: |
75 |
| Institution: |
Università degli Studi di Napoli Federico II |
| Department: |
Biologia e patologia cellullare e molecolare "L. Califano" |
| Scuola di dottorato: |
Medicina molecolare |
| Dottorato: |
Patologia e fisiopatologia molecolare |
| Ciclo di dottorato: |
21 |
| Coordinatore del Corso di dottorato: |
| nome | email |
|---|
| Avvedimento, Vittorio Enrico | avvedim@unina.it |
|
| Tutor: |
| nome | email |
|---|
| Condorelli, Gerolama | UNSPECIFIED |
|
| Date: |
11 December 2008 |
| Number of Pages: |
75 |
| Uncontrolled Keywords: |
Contrast media, Kidney, Apoptosis, Prevention |
| Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
| Date Deposited: |
06 Nov 2009 10:23 |
| Last Modified: |
30 Apr 2014 19:35 |
| URI: |
http://www.fedoa.unina.it/id/eprint/3073 |
| DOI: |
10.6092/UNINA/FEDOA/3073 |
Abstract
Contrast media (CM) induce a direct toxic effect on renal tubular cells. This toxic effect may have a role in the
pathophysiology of contrast nephropathy.
I evaluated: (i) the cytotoxicity of CM [both low-osmolality (LOCM) and iso-osmolality (IOCM)], of iodine alone,and of an hyperosmolar solution (mannitol 8%) on human embryonic kidney (HEK 293), porcine proximal renal
tubular (LLC-PK1), and canine Madin–Darby distal tubular renal (MDCK) cells; and (ii) the effectiveness of
various antioxidant compounds [N-acetylcysteine (NAC), ascorbic acid and sodium bicarbonate] in preventing CM
cytotoxicity. The cytotoxicity of CM was assessed at different time points, with different methods: cell viability,DNA laddering, flow cytometry, and caspase activation.
Both LOCM and IOCM produced a concentration- and time-dependent increase in cell death as assessed by the
different methods. On the contrary, iodine alone and hyperosmolar solution did not induce any significant cytotoxic effect. There was not any significant difference in the cytotoxic effect between LOCM and IOCM. Furthermore, both LOCM and IOCM caused a marked increase in caspase-3 and -9 activities and poly(ADP-ribose) fragmentation, while
no effect on caspase-8/-10 was observed, thus indicating that the CM activated apoptosis mainly through the intrinsic
pathway. Both CM induced an increase in protein expression levels of pro-apoptotic members of the Bcl2 family (Bim
and Bad). NAC and ascorbic acid but not sodium bicarbonate had a dose-dependent protective effect on renal cells
after 3 h incubation with high dose (200 mg iodine/mL) of both LOCM and IOCM. Both LOCM and IOCM induce a dose-dependent renal cell apoptosis. NAC and ascorbic acid but not sodium bicarbonate prevent this contrast-induced apoptosis.
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