Korean J Physiol Pharmacol.  2021 Jul;25(4):261-272. 10.4196/kjpp.2021.25.4.261.

Protective effects and mechanism of coenzyme Q10 and vitamin C on doxorubicin-induced gastric mucosal injury and effects of intestinal flora

• Zhao X
• Feng X
• Ye N
• Wei P
• Zhang Z
• Lu W

• KMID: 2516866
• DOI: http://doi.org/10.4196/kjpp.2021.25.4.261

Abstract

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKβ, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora.

Keyword

Coenzyme Q10; Doxorubicin; NF-κB pathway; Vitamin C

Figure

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  Fig. 1 Schematic diagram of experiment. i.g., intragastric administration; i.v., intravenous injection; Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C.

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  Fig. 2 Effects of Dox, VC and CoQ10 on the apoptosis of GES-1 cells (×100 magnification). Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C.

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  Fig. 3 Effects of Dox, VC and CoQ10 on the expression of IκKβ, IκBα, NF-κB/p65 and TNF-α protein levels in GES-1 cells. Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C. *p < 0.05 (vs. control); **p < 0.01 (vs. control); ##p < 0.01 (vs. Dox).

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  Fig. 4 The expression of GSH and MDA in gastric tissue of different groups. GSH, glutathione; MDA, malondialdehyde; Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C. **p < 0.01 (vs. control); #p < 0.05 (vs. Dox); and ##p < 0.01 (vs. Dox).

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  Fig. 5 The expression levels of TNF-α, IL-6 and INF-γ mRNA in gastric tissue of different groups. Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C. *p < 0.05 (vs. control); **p < 0.01 (vs. control); #p < 0.05 (vs. Dox); ##p < 0.01 (vs. Dox).

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  Fig. 6 Weighted Unifrac heatmap. Dox, doxorubicin; C, coenzyme Q10; V, vitamin C.

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  Fig. 7 Venn diagrams of OTUs included in four groups. We grouped all gastric tissue samples into Blank, V-Dox, C-Dox, Dox, representing blank control group, VC-Dox treatment group, CoQ10-Dox treatment group, Dox treatment group, respectively. Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C.

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  Fig. 8 Species distribution stacked graph. Dox, doxorubicin; C, coenzyme Q10; V, vitamin C.

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  Fig. 9 Pathway abundance heat map. Dox, doxorubicin; CoQ10, coenzyme Q10; VC, vitamin C.

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  Fig. 10 LEFse difference analysis diagram. Dox, doxorubicin.

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