title: Supplementation of fish oil augments efficacy and attenuates toxicity of 5-fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium-induced colon carcinogenesis.
abstract: OBJECTIVE
  5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer, but has low therapeutic response rate and severe side effects. Recently, fish oil (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anticancer drugs. Therefore, the current study is designed to evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)-induced colon cancer model.
  
  
  METHODS
  The therapeutic efficacy of 5-FU along with FO was analyzed through assessment of survival rate, tumor burden, volume, serum sialic acid levels, cytokeratin 19 (CK19) expression and index of cell proliferation such as cell cycle progression. Toxicological aspects were evaluated by standard functional and structural parameters related to spleen, gastrointestinal, liver and kidney.
  
  
  RESULTS
  In the present study, 5-FU in combination with FO increased the survival rate in carcinogen-treated animals. Synergism of 5-FU and FO was also reflected in significant inhibition in tumor growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination dosage significantly augmented the inhibition of cell cycle progression, as shown by CK19 expression. Additionally, FO ameliorated hematologic depression, gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a marked improvement in structural and functional alterations of these organs.
  
  
  CONCLUSIONS
  The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh, 160014, India.
authors.forename: Isha
authors.initials: I
authors.lastname: Rani
authors.forename: Kim
authors.initials: K
authors.lastname: Vaiphei
authors.forename: Navneet
authors.initials: N
authors.lastname: Agnihotri
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity*; D019587:Dietary Supplements; D005395:Fish Oils / Q000627:therapeutic use*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000964:Antimetabolites, Antineoplastic; D002273:Carcinogens; D005395:Fish Oils; D016264:Dextran Sulfate; D019813:1,2-Dimethylhydrazine; D005472:Fluorouracil