Aged Garlic Extract Protects against Methotrexate-Induced Apoptotic Cell Injury of IEC-6 Cells

Abstract

Gastrointestinal toxicity is one of the most serious side effects of methotrexate (MTX) treatment. The side effects often disrupt the cancer chemotherapy. We previously reported that aged garlic extract (AGE) protects the small intestine of rats from MTX-induced damage. In this study, the protection of AGE against MTX-induced damage of IEC-6 cells originating from the rat jejunum crypt was investigated. MTX decreased the viability of IEC-6 cells, but this effect was prevented by AGE (0.5%). The MTX-induced apoptosis of IEC-6 cells was depressed by AGE. These results indicated that AGE protects IEC-6 cells from the MTX-induced damage. AGE may be useful in cancer chemotherapy with MTX because it reduces MTX-induced intestinal damage.

The effect of mirtazapine on methotrexate-induced toxicity in rat liver

“…In contrast, in the MMTX group there were only a few necrotic cells. Previous studies have also shown that methotrexate intensifies apoptosis 23 . Caspase is a gene that controls cell apoptosis.…”

Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

“…13,32 5-FU inhibited normal intestinal cell proliferation and reduced villus height in rats, 30 while Methotrexate (MTX), another anti-metabolite chemotherapy drug, has been shown to decrease viability and induce apoptosis in IEC-6 cells. 33 Smaller PAs (3-7mers) are thought to not cross the intestinal barrier and remain bioactive in the gut. 34 Erlejman et al 34 demonstrated that hexameric procyanidins were most effective in preventing oxidative damage in Caco-2 colonic cells.…”

“…GSE represents a readily available source of polyphenols, which is particularly rich in PAs. 21 In the current study, IEC-6 cells were used in an in vitro assay of normal intestinal cell 5-FU damage as they are non-malignant intestinal cells derived from rat ileum 33 and have been previously used to study gastrointestinal toxicity such as that induced by MTX. 33 Exposure of IEC-6 cells to 5-FU greatly reduced IEC-6 cell viability relative to non-damaged control cells, as measured by neutral red assay.…”

“…21 In the current study, IEC-6 cells were used in an in vitro assay of normal intestinal cell 5-FU damage as they are non-malignant intestinal cells derived from rat ileum 33 and have been previously used to study gastrointestinal toxicity such as that induced by MTX. 33 Exposure of IEC-6 cells to 5-FU greatly reduced IEC-6 cell viability relative to non-damaged control cells, as measured by neutral red assay. However, cell viability was restored by GSE pre-incubation of 35 demonstrated that GSE was effective against other classes of chemotherapy drugs.…”

Salvia miltiorrhiza causes tonic contraction in rat ileum through Ca2+-calmodulin pathway

“…IEC-6 cells have the characteristics of crypttype intestinal cells and have been extensively used as an in vitro intestinal model for gastrointestinal regeneration (Horie et al, 2006;Santos et al, 1997). In the present study, the SM extracts induce extracellular Ca 2 þ entry and massive intracellular Ca 2 þ release in Ca 2 þ -contained medium, and induce intracellular Ca 2 þ release in Ca 2 þ -free medium.…”