Protective effect of curcumin on chemotherapy-induced intestinal dysfunction.
OBJECTIVE
Chemotherapy is one of most important treatments for human cancers. However, side effects such as intestine dysfunction significantly impaired its clinical efficacy. This study aimed to investigate the protective effect of Curcumin on chemotherapy-induced intestinal dysfunction in rats.


METHODS
Sixty healthy Wistar rats were randomly divided into control group (normal saline), 5-FU group and 5-FU+Curcumin group. The weight, serum level of endotoxin, DAO and D-lactate were determined. The pathological change of intestinal mucosa structure was studied under light microscopy and electron microscopy. The expression of Bax, Bcl-2 and Caspase-3 were assessed by immunohistochemical staining.


RESULTS
The Curcumin intragastrically administrated obviously reduced 5-FU-induced weight-loss. 5-FU induced dramatic increase of serum endotoxin, D-lactate and D-Amino-Acid Oxidase (DAO) that were significantly reversed by Curcumin treatment. Meanwhile, 5-FU-induced-damage to intestinal mucosa structure was markedly recovered by Curcumin. The expression of Bax and Caspase-3 were dramatically increased after 5-FU treatment (p<0.01) and Curcumin treatment significantly reduced Bax expression (p<0.05) but had only a moderate effect on reducing caspase-3 expression (p>0.05). Interestingly, Bcl-2 expression was low in control group but increased after 5-FU treatment (p>0.05) and Curcumin treatment further stimulated Bcl-2 expression (p<0.05).


CONCLUSIONS
Curcumin can significantly reverse chemotherapy-induced weight-loss, increase of serum endotoxin, D-lactate and DAO and damage to intestinal mucosa structure. Curcumin also reduced the expression of pro-apoptotic Bax but stimulated anti-apoptotic Bcl-2 to attenuate 5-FU-induced apoptosis of intestinal epithelial cells. The clinical administration of Curcumin may improve chemotherapy-induced intestinal dysfunction, thus increasing the clinical efficacy of chemotherapy.
Department of Oncology, The First Affiliated Hospital of Zhejiang Traditional Chinese Medical University Hangzhou, Zhejiang Province, China.
Qinghua
Q
Yao
Xiaozheng
X
Ye
Lu
L
Wang
Jianzhong
J
Gu
Ting
T
Fu
Yun
Y
Wang
Yuebiao
Y
Lai
Yuqi
Y
Wang
Xian
X
Wang
Hongchuan
H
Jin
Yong
Y
Guo
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection; D003605:D-Amino-Acid Oxidase / Q000097:blood; D004731:Endotoxins / Q000097:blood; D005472:Fluorouracil / Q000633:toxicity*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019344:Lactic Acid / Q000097:blood; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C494828:Bax protein, rat; D015415:Biomarkers; D004731:Endotoxins; D020011:Protective Agents; D051028:bcl-2-Associated X Protein; D019344:Lactic Acid; D003605:D-Amino-Acid Oxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D003474:Curcumin; D005472:Fluorouracil
5-FU; Bax; Bcl-2; Curcumin; chemotherapy-induced; intestinal dysfunction; ultrastructures