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Updated: Mar 23, 2026
Analyzing Oxidative Stress in Murine Intestinal Organoids using Reactive Oxygen Species-Sensitive Fluorogenic Probe
Published on: September 17, 2021
Oxidative stress balance is dysregulated and represents an additional target for treating cholangiocarcinoma
Daisuke Uchida1, Akinobu Takaki1, Hisashi Ishikawa1
1a Department of Gastroenterology and Hepatology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan ;
Background:
Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model.
Methods:
We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy.
Results:
Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. l-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers.
Conclusion:
Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent l-carnitine is a good candidate to control oxidative stress conditions.
Insights
Oxidative stress imbalance is linked to poor outcomes in cholangiocarcinoma. L-carnitine shows promise in managing oxidative stress, unlike vitamin E, which increased stem-like cells in a mouse model.
Area of Science:
- Oncology
- Biochemistry
- Gastroenterology
Background:
- Pancreatic-biliary malignancies share obesity links and poor prognoses, necessitating novel treatments.
- Oxidative stress plays a dual role in cancer, inducing DNA damage but also possessing anti-infection and anti-cancer properties.
- Understanding oxidative stress's impact on cancer progression is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To evaluate oxidative stress and antioxidant balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients.
- To investigate the effect of add-on antioxidant therapy on chemotherapy in a mouse cholangiocarcinoma model.
Main Methods:
- Recruited 84 CC and 80 PC patients.
- Measured serum reactive oxygen metabolites (ROM) and OXY-adsorbent test levels to determine the oxidative index.
- Utilized a diabetic mouse model to assess antioxidant therapy effects on cholangiocarcinoma.
Main Results:
- CC patients with poor outcomes showed higher ROM and lower antioxidant OXY levels; PC patients showed no significant differences.
- In mice, vitamin E increased stem-like cells and hemeoxygenase (HO)-1 expression.
- L-carnitine improved gut microbiome and bile acid balance, upregulating Cpt1 gene expression without affecting stem-like cells.
Conclusions:
- Oxidative stress dysregulation is associated with poor outcomes in cholangiocarcinoma.
- L-carnitine, a mitochondrial function supporter, is a potential agent for managing oxidative stress in CC.
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