Abstract | INTRODUCTION: AIM: MATERIALS AND METHODS: Male Swiss mice were treated intraperitoneal (i.p.) with saline (control), glutathione (125, 250 or 500 mg/kg) or amifostine (25, 50 or 100 mg/kg), and 30 min later they received a single i.p. injection of IFS at a dose of 400 mg/kg. To investigate the systemic effects of the antioxidants on ACR-induced HC, the animals were treated with saline, amifostine (50 mg/kg, i.p.) or glutathione (500 mg/kg, i.p.), and 30 min afterward with 75 mug ACR intravesically (i.ve.). In another set of experiments, the antioxidants were injected directly into the bladder, where the mice received a single i.ve injection of ACR (75 mug) plus amifostine (1.5 mg/kg) or glutathione (2 mg/kg). HC was measured 3 h after IFS or ACR injection according to bladder wet weight, macroscopic ( edema and hemorrhage) and microscopic changes, i.e., edema, hemorrhage, cellular infiltration, fibrin deposition and urothelial desquamation. RESULTS: Pretreatments with amifostine or glutathione prevented IFS-induced HC in a dose-dependent manner. Furthermore, ACR-induced HC was also prevented by systemic (i.p.) or local (i.ve.) pretreatment with glutathione or amifostine. The greatest protective effect was seen with local amifostine treatment (2 mg/kg i.ve.) (P < 0.05). CONCLUSIONS:
Glutathione and amifostine show a beneficial effect in experimental IFS- and ACR-induced HC. Thus, they should be investigated as an alternative treatment to prevent HC observed in patients undergoing IFS treatment.
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Authors | C K L P Batista, J M S C Mota, M L P Souza, B T A Leitão, M H L P Souza, G A C Brito, F Q Cunha, R A Ribeiro |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 59
Issue 1
Pg. 71-7
(Jan 2007)
ISSN: 0344-5704 [Print] Germany |
PMID | 16708234
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antidotes
- Antineoplastic Agents, Alkylating
- Radiation-Protective Agents
- Acrolein
- Glutathione
- Amifostine
- Ifosfamide
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Topics |
- Acrolein
(antagonists & inhibitors, toxicity)
- Amifostine
(therapeutic use)
- Animals
- Antidotes
(therapeutic use)
- Antineoplastic Agents, Alkylating
(antagonists & inhibitors, toxicity)
- Cystitis
(chemically induced, pathology, prevention & control)
- Dose-Response Relationship, Drug
- Edema
(chemically induced, pathology, prevention & control)
- Glutathione
(therapeutic use)
- Hemorrhage
(chemically induced, pathology, prevention & control)
- Ifosfamide
(antagonists & inhibitors, toxicity)
- Injections, Intraperitoneal
- Injections, Intravenous
- Male
- Mice
- Radiation-Protective Agents
(therapeutic use)
- Urinary Bladder
(pathology)
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