Protective effect of aged garlic extract (AGE) on the apoptosis of intestinal epithelial cells caused by methotrexate

Li, Tiesong; Ito, Kousei; Sumi, Shin-ichiro; Fuwa, Tohru; Horie, Toshiharu

doi:10.1007/s00280-008-0809-4

Cited by 27 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Caspase-3, the main downstream effector, cleaves the majority of cellular substrates in apoptotic cells (21,35). Several studies showed that caspase-3 activity was increased in the process of intestinal apoptosis during chemotherapy, including 5-FU treatment (5,25,44). We observed a marked increase in immunopositive cells for cleaved caspase-3, the active form of caspase-3, which localized to the intestinal crypt in a manner consistent with the localization of apoptotic cells in WT mice.…”

Section: Discussionsupporting

confidence: 51%

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Yasuda

Kato

Yamanaka

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

. Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice. Am J Physiol Gastrointest Liver Physiol 302: G1133-G1142, 2012. First published March 7, 2012 doi:10.1152/ajpgi.00535.2011.-Although NADPH oxidase 1 (NOX1) has been shown to be highly expressed in the gastrointestinal tract, the physiological and pathophysiological roles of this enzyme are not yet fully understood. In the present study, we investigated the role of NOX1 in the pathogenesis of intestinal mucositis induced by the cancer chemotherapeutic agent 5-fluorouracil (5-FU) in mice. Intestinal mucositis was induced in Nox1 knockout (Nox1KO) and littermate wild-type (WT) mice via single, daily administration of 5-FU for 5 days. In WT mice, 5-FU caused severe intestinal mucositis characterized by a shortening of villus height, a disruption of crypts, a loss of body weight, and diarrhea. In Nox1KO mice, however, the severity of mucositis was significantly reduced, particularly with respect to crypt disruption. The numbers of apoptotic caspase-3-and caspase-8-activated cells in the intestinal crypt increased 24 h after the first 5-FU administration but were overall significantly lower in Nox1KO than in WT mice. Furthermore, the 5-FU-mediated upregulation of TNF-␣, IL-1␤, and NOX1 and the production of reactive oxygen species were significantly attenuated in Nox1KO mice compared with that in WT mice. These findings suggest that NOX1 plays an important role in the pathogenesis of 5-FU-induced intestinal mucositis. NOX1-derived ROS production following administration of 5-FU may promote the apoptotic response through upregulation of inflammatory cytokines.

show abstract

Section: Discussionsupporting

confidence: 51%

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Yasuda

Kato

Yamanaka

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Gao and Horie [3] showed that MTX inhibits the de novo purine synthesis and thymidine kinase in the salvage pathway of pyrimidine synthesis in crypt cells of the small intestine, leading to villous degeneration. Li et al [12] reported that MTX treatment increases the cell death and decreases cell number in the intestinal epithelium. In our study, MTX treatment was associated with damage to intestinal tissue in the form of villous shortening, epithelial atrophy, crypt loss, inflammatory cells infiltration in the lamina propria and goblet cell loss .…”

Section: Discussionmentioning

confidence: 98%

Protective role of lipoic acid on methotrexate induced intestinal damage in rabbit model

Somi

Hajipour

Abad

et al. 2011

Indian J Gastroenterol

View full text Add to dashboard Cite

Methotrexate (MTX), a folate antagonist agent, is mainly used in treatment of malignant tumors and auto immune diseases and affects not only tumor cells, but also gastrointestinal mucosa. The present study was undertaken to determine whether lipoic acid (LA) could ameliorate methotrexate-induced oxidative intestine injury in rabbits. Twenty-one rabbits were randomly assigned into three groups: Group 1 (control group), Group 2 (received 20 mg/kg MTX), Group 3 (received MTX plus LA 75 mg/kg orally). On the 6th day rabbits were anesthetized and intestinal tissue sampled for pathologic and biochemical assessment. The intestinal tissue injury index and malondialdehyde (MDA) levels were lower in MTX+LA group as compared to the MTX group, and tissue glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were higher in MTX+LA group than in the MTX group (p < 0.05). These findings suggest that co-administration of LA with MTX is associated with reduction in oxidative injury and tissue damage in the intestine. We suggest that lipoic acid may have a protective role in the MTX-induced oxidative injury.

show abstract

“…Conversely, certain natural products have protective effects against apoptosis. Ginkgo biloba extract protected rat pheochromocytoma (PC12) cells from possible oxidative damage induced by trophic factors and garlic extracts are also protective against the apoptosis of intestinal epithelial cells caused by methotrexate (28,29). Therefore, the effect of natural products on mitochondrial function remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Bak is a key molecule in apoptosis induced by methanol extracts of Codonopsis lanceolata and Tricholoma matsutake in HSC-2 human oral cancer cells

Shin

Kim²,

Hong

et al. 2012

Oncology Letters

View full text Add to dashboard Cite

Abstract. Since the 5-year survival rate of oral cancer remains low, more effective and non-toxic therapeutic and preventive strategies are required. Certain natural products possess anticancer properties. The present study investigated the effects of the methanol extracts of Codonopsis lanceolata (MECI) and Tricholoma matsutake (METM) and identified the molecular target in HSC-2 human oral cancer cells. The results revealed that MECI and METM inhibited growth and induced apoptosis, as demonstrated by poly (ADP-ribose) polymerase (PARP) cleavage and nuclear condensation and fragmentation. The compounds also increased Bak protein expression, while Bax, Bcl-XL and Mcl-1 were not affected. The results of the present study show that MECI and METM induce apoptosis to inhibit tumor growth of HSC-2 cells by modulating the Bak protein and suggest that Codonopsis lanceolata and Tricholoma matsutake are potential anticancer drug candidates for oral cancer.

show abstract

Protective effect of aged garlic extract (AGE) on the apoptosis of intestinal epithelial cells caused by methotrexate

Abstract: The MTX-induced apoptosis of IEC-6 cells was shown to be depressed by AGE. AGE may be useful for the cancer chemotherapy with MTX, since AGE reduces the MTX-induced intestinal damage.

Cited by 27 publications

References 34 publications

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Protective role of lipoic acid on methotrexate induced intestinal damage in rabbit model

Bak is a key molecule in apoptosis induced by methanol extracts of Codonopsis lanceolata and Tricholoma matsutake in HSC-2 human oral cancer cells

Contact Info

Product

Resources

About