Electroacupuncture at the “Zusanli(ST36)” acupoints alleviates 5-fluorouracil-induced renal injury in colorectal cancer-bearing mice by exerting effects on oxidative stress, inflammatory responses, and cell apoptosis

Chemotherapy is a major treatment modality for colorectal cancer. It can be used in colorectal cancer patients who have recurrent disease or are ineligible for surgery and as postoperative adjuvant therapy. Chemotherapy drugs inhibit tumor growth by blocking the growth and proliferation of tumor cells. However, such drugs exert killing effects on both tumor cells and normal cells of the body. This leads to the emergence of different types and degrees of toxic side effects from the clinical use of chemotherapy drugs, which seriously affect the quality of life and survival of patients [1]. Among the various types of side effects, tumor-associated renal injury has been extensively studied in the field of renal disease [2].

5-fluorouracil (5-FU) is the first-choice chemotherapy drug for patients with mid- to late-stage colorectal cancer who are not candidates for surgery. It is also the most commonly used uracil-based antimetabolite drug in clinical practice. It induces the apoptosis of tumor cells mainly by interfering with DNA synthesis and mRNA translation [3]. 5-FU is considered a nephrotoxic compound that induces oxidative stress [4], inflammatory responses, and cell apoptosis [5] in renal tissue. During redox imbalance in cells, excess reactive oxygen species (ROS) act on biomolecules such as lipids, proteins, and DNA [6], and are capable of activating NF-κB [7], leading to inflammatory responses and apoptosis in cells. Various degrees of renal injury such as glomerulosclerosis, atrophy of convoluted tubules, and interstitial fibrosis may then occur in the kidneys, ultimately resulting in renal dysfunction [8].

The bilateral “ST36” acupoints are located on the foot yangming stomach meridian. Modern research has reported that electroacupuncture(EA) at "ST36" reduces renal oxidative stress and attenuates renal injury in type 2 diabetic rats [9], and is capable of inhibiting endoplasmic reticulum (ER) stress, reducing renal cell apoptosis [10], inhibiting inflammatory factors, and alleviating immune disorders in the kidneys [11]. Acupuncture therapy can reduce adverse reactions induced by chemotherapy drugs. Given the scarcity of research on the effects of acupuncture in the prevention and treatment of chemotherapy-associated renal injury, the present study aimed to construct a colorectal cancer-bearing mouse model to observe whether EA at “ST36” attenuates renal injury caused by 5-FU chemotherapy through the regulation of oxidative stress, inflammatory responses, and cell apoptosis. Our results can provide experimental support for the use of acupuncture to treat post-chemotherapy renal injury.

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