Omega-3 fatty acids are able to modulate the painful symptoms associated to cyclophosphamide-induced-hemorrhagic cystitis in mice.
This study investigated the effects of the long-term dietary fish oil supplementation or the acute administration of the omega-3 fatty acid docosahexaenoic acid (DHA) in the mouse hemorrhagic cystitis (HC) induced by the anticancer drug cyclophosphamide (CYP). HC was induced in mice by a single CYP injection (300mg/kg ip). Animals received four different diets containing 10% and 20% of corn or fish oil, during 21days. Separated groups received DHA by ip (1μmol/kg) or intrathecal (i.t.; 10μg/site) routes, 1h or 15min before CYP. The behavioral tests (spontaneous nociception and mechanical allodynia) were carried out from 1h to 6h following CYP injection. Bladder inflammatory changes, blood cell counts and serum cytokines were evaluated after euthanasia (at 6h). Immunohistochemistry analysis was performed for assessing spinal astrocyte and microglia activation or GPR40/FFAR1 expression. Either fish oil supplementation or DHA treatment (ip and i.t.) markedly prevented visceral pain, without affecting CYP-evoked bladder inflammatory changes. Moreover, systemic DHA significantly prevented the neutrophilia/lymphopenia caused by CYP, whereas this fatty acid did not significantly affect serum cytokines. DHA also modulated the spinal astrocyte activation and the GPR40/FFAR1 expression. The supplementation with fish oil enriched in omega-3 fatty acids or parenteral DHA might be interesting nutritional approaches for cancer patients under chemotherapy schemes with CYP.
PUCRS, Programa de Pós-Graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brasil; PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brasil.
Raquel D S
RD
Freitas
PUCRS, Programa de Pós-Graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brasil; PUCRS, Laboratório de Genômica e Biologia Molecular, Faculdade de Biociências, Porto Alegre, RS, Brasil; PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brasil.
Kesiane M
KM
Costa
PUCRS, Programa de Pós-Graduação em Biologia Celular e Molecular, Porto Alegre, RS, Brasil; PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brasil.
Natália F
NF
Nicoletti
PUCRS, Programa de Pós-Graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brasil; PUCRS, Laboratório de Genômica e Biologia Molecular, Faculdade de Biociências, Porto Alegre, RS, Brasil.
Luiza W
LW
Kist
PUCRS, Programa de Pós-Graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brasil; PUCRS, Programa de Pós-Graduação em Biologia Celular e Molecular, Porto Alegre, RS, Brasil; PUCRS, Laboratório de Genômica e Biologia Molecular, Faculdade de Biociências, Porto Alegre, RS, Brasil; PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brasil.
Maurício R
MR
Bogo
PUCRS, Programa de Pós-Graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brasil; PUCRS, Programa de Pós-Graduação em Biologia Celular e Molecular, Porto Alegre, RS, Brasil; PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brasil; PUCRS, Faculdade de Odontologia, Porto Alegre, RS, Brasil. Electronic address: maria.campos@pucrs.br.
Maria M
MM
Campos
D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D001743:Urinary Bladder / Q000201:enzymology
D015525:Fatty Acids, Omega-3; D003520:Cyclophosphamide; D009195:Peroxidase
Cyclophosphamide; DHA; GPR40; Hemorrhagic cystitis; Mice; Omega-3