Abstract
PurposeHigh-dose chemotherapy using methotrexate (MTX) frequently induces side effects such as mucositis that leads to intestinal damage and diarrhea. Several natural compounds have been demonstrated of their effectiveness in protecting intestinal epithelial cells from these adverse effects. In this paper, we investigated the protection mechanism of lutein against MTX-induced damage in IEC-6 cells originating from the rat jejunum crypt.MethodsThe cell viability, induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential in IEC-6 cells under MTX treatment were examined in the presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR.ResultsThe cell viability of IEC-6 cells exposed to MTX was decreased in a dose- and time-dependent manner. MTX induces mitochondrial membrane potential loss, ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre-treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The expression of SOD was up-regulated by the pre-treatment of lutein in the MTX-treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells from the chemo-drugs induced damage through increasing ROS scavenging ability.ConclusionThe MTX-induced apoptosis of IEC-6 cells was shown to be repressed by the pre-treatment of lutein, which may represent a promising adjunct to conventional chemotherapy for preventing intestinal damages.
Highlights
Cancers are leading causes of mortality in both adults and children
The effect of MTX is attributed to its inhibition of dihydrofolate reductase, purine synthesis or blocking DNA repair, but can cause an acute injury to the intestinal epithelium characterized by reduced mitosis in the crypts and shortened villi [1,2]
We examined the effects of lutein to protect the intestine from MTX-induced cytotoxic injuries in an IEC-6 intestinal epithelial cell chemotherapy damage model
Summary
Cancers are leading causes of mortality in both adults and children. Multiple drugs have been developed to treat cancers. MTX is known as a pro-oxidant compound that causes depletion of the dihydrofolate pool It directly affects the synthesis of thymidilate, suppresses DNA synthesis, inhibits epithelial proliferation, and induces apoptosis in the small intestinal crypts [7]. In order to minimize the side effects in patients taking MTX as chemotherapeutic agent, it is important to reduce the damages and to stimulate tissue repair [9]. Growth factors such as insulin-like growth factor 1 and keratinocyte growth factor were reported to protect mice from gastrointestinal injury by stimulating growth of the damaged intestine [10,11]. Other studies using vitamin A [6,12], aged garlic extract (AGE) [8], apricot, beta-carotene [13], melatonin [14] and prostaglandins [15], showed protective effect on the MTX-induced damages to the small intestine in rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
