title: Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice.
abstract: Oxaliplatin (OXA) is a platinum compound widely used in the treatment of some solid tumors, especially colorectal cancer. Despite its usefulness, oxaliplatin-associated neurotoxicity represents the main dose-limiting factor of this drug, and until now, there is no suitable treatment. Chemotherapy with oxaliplatin also increases the rate of developing hepatic damages with inflammatory activity, termed chemotherapy-associated steatohepatitis (CASH). In the present study, we aimed to compare the effects of a series of antioxidant compounds on simultaneous development of oxaliplatin-induced hepato- and neurotoxicity in mice. Mice BALB/c were treated with oxaliplatin for 6 weeks, 10 mg/kg, intraperitoneally, resulting in mechanical allodynia and hepatic steatosis. We administered the following antioxidant compounds--rutin (RT) (20 mg/kg), resveratrol (RVS) (100 mg/kg), quercetin (QT) (20 mg/kg), and quercetin nanoemulsion (NQT) (20 mg/kg)--daily by gavage to BALB/c, and N-acetylcysteine (NAC) was used as positive control. Treatments with RSV, RUT, or NQT were able to prevent mechanical allodynia when compared to the OXA group, and this effect was associated with decreased c-Fos immunopositivity in the lumbar spinal cord. Regarding the effects on steatohepatitis, RVS, QT, and NQT almost completely reversed the mean liver weight increase induced by OXA. In accordance with these previous data, histological evaluation indicated attenuation of all features of hepatic steatosis evaluated in RSV, RUT, QT, and NQT groups. These compounds were able to reduce the immunopositivity for the apoptosis marker caspase-3. On the other hand, only QT and NQT treatments were able to reduce neutrophil migration measured by myeloperoxidase (MPO) activity. These results suggest that the compounds tested, RSV, RUT, QT, and NQT, would be useful for the clinical treatment of neuro- and hepatoxicity induced by oxaliplatin.
authors.affiliation: Programa de Pós Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Tania E
authors.initials: TE
authors.lastname: Schwingel
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Klein
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Nicoletti
authors.forename: Cristiana L
authors.initials: CL
authors.lastname: Dora
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hadrich
authors.forename: Cláudia G
authors.initials: CG
authors.lastname: Bica
authors.forename: Tiago G
authors.initials: TG
authors.lastname: Lopes
authors.forename: Vinicius Duval
authors.initials: VD
authors.lastname: da Silva
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Morrone
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D004655:Emulsions; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy; D008159:Lumbar Vertebrae; D008297:Male; D008807:Mice, Inbred BALB C; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000378:metabolism; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D009195:Peroxidase / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology / Q000627:therapeutic use*; D000077185:Resveratrol; D012431:Rutin / Q000494:pharmacology / Q000627:therapeutic use*; D013116:Spinal Cord / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D009944:Organoplatinum Compounds; D016760:Proto-Oncogene Proteins c-fos; D013267:Stilbenes; D000077150:Oxaliplatin; D012431:Rutin; D011794:Quercetin; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D000077185:Resveratrol