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Review
. 2022 May 9:2022:7255497.
doi: 10.1155/2022/7255497. eCollection 2022.

The Intestinal Redox System and Its Significance in Chemotherapy-Induced Intestinal Mucositis

Qing-Qing Yu  1   2 , Heng Zhang  3 , Yujin Guo  2 , Baoqin Han  1   4 , Pei Jiang  2
Affiliations
Review

The Intestinal Redox System and Its Significance in Chemotherapy-Induced Intestinal Mucositis

Qing-Qing Yu et al. Oxid Med Cell Longev. .

Abstract

Chemotherapy-induced intestinal mucositis (CIM) is a significant dose-limiting adverse reaction brought on by the cancer treatment. Multiple studies reported that reactive oxygen species (ROS) is rapidly produced during the initial stages of chemotherapy, when the drugs elicit direct damage to intestinal mucosal cells, which, in turn, results in necrosis, mitochondrial dysfunction, and ROS production. However, the mechanism behind the intestinal redox system-based induction of intestinal mucosal injury and necrosis of CIM is still undetermined. In this article, we summarized relevant information regarding the intestinal redox system, including the composition and regulation of redox enzymes, ROS generation, and its regulation in the intestine. We innovatively proposed the intestinal redox "Tai Chi" theory and revealed its significance in the pathogenesis of CIM. We also conducted an extensive review of the English language-based literatures involving oxidative stress (OS) and its involvement in the pathological mechanisms of CIM. From the date of inception till July 31, 2021, 51 related articles were selected. Based on our analysis of these articles, only five chemotherapeutic drugs, namely, MTX, 5-FU, cisplatin, CPT-11, and oxaliplatin were shown to trigger the ROS-based pathological mechanisms of CIM. We also discussed the redox system-mediated modulation of CIM pathogenesis via elaboration of the relationship between chemotherapeutic drugs and the redox system. It is our belief that this overview of the intestinal redox system and its role in CIM pathogenesis will greatly enhance research direction and improve CIM management in the future.

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Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
The anatomical, cellular, and subcellular locations of the intestinal oxidoreductases. The anatomical location of oxidoreductase is shown in red color (the top line). The cellular and subcellular locations of oxidoreductases are represented by yellow or brown color.
Figure 2
Figure 2
Intestinal redox regulation. OS regulation via oxidoreductases maintains normal physiological intestinal homeostasis, similar to the balance of the “Tai Chi” theory. The regulation of NOX, CAT, PRDX, and NOS was mainly at the posttranslational level; the others were at the translational level.
Figure 3
Figure 3
The intestinal oxidation-reduction (redox) system “Tai Chi” in normal physiological function. To support normal physiological function, the level of redox species was maintained in a certain limitation using subtle and complex regulatory methods, including local (induced by the oxidoreductases in different cell, tissue, and organ location) and global (induced by the products of oxidoreductases inside and outside the cell, even inside and outside the intestine) horizontal regulation. Additionally, the intestinal physiological function mainly includes the absorption of nutrients (water with the white point and inorganic salt with the black point) and the defense against pathogenic microorganisms.
Figure 4
Figure 4
A flow diagram of the identification of articles included in this review.
Figure 5
Figure 5
The intestinal oxidation-reduction (redox) “Tai Chi” system in CIM pathogenesis. MTX, 5-FU, cisplatin, CPT-11, and oxaliplatin induced high levels of O2−, H2O2, NO, and HA via regulation of oxidoreductases, which disrupted the balance of intestinal redox “Tai Chi” system, and resulted in apoptosis and inflammation of the intestine, which contributed to the pathogenesis of CIM.
Figure 6
Figure 6
The mechanism of CIM treatment strategies in studies included in this review. The treatment strategies can be divided into 3 categories, according to the targets: proanthocyanidins, UFMG A-905, rutin, salecan, melatonin, and magnolol target redox and inflammation; lutein and pomegranate juice target redox and apoptosis; and vitamin E and FITOPROT target redox, inflammation, and apoptosis.
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