Mesenchymal stem cells have ameliorative effect on the colitis model via Nrf2/HO-1 pathway

Bozkurt, Mehmet Fatih; Bhaya, Muhammed Nasir; Dibekoğlu, Cengiz; Akat, Ayberk; Ateş, Utku; Erbaş, Oytun

doi:10.1590/acb370704

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Acta Cirúrgica Brasileira

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Sumário

ORIGINAL ARTICLE • Acta Bras Cir 37 (7) • 2022 • https://doi.org/10.1590/acb370704 copy

Mesenchymal stem cells have ameliorative effect on the colitis model via Nrf2/HO-1 pathway

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Purpose:

To evaluate the ameliorative effect of mesenchymal stem cells (MSCs) on acetic acid colitis model via Nrf2/HO-1 pathway in rats.

Methods:

In this study, 30 rats were divided into three groups. Acute colitis was induced by rectal administration of 4% solution of acetic acid. MSCs were injected intraperitoneally in the treatment group.

Results:

Increased levels of tumor necrosis factor-α (TNF-α), pentraxin-3, and malondialdehyde (MDA) in colitis group were revealed biochemically. Increased level of TNF-α and decreased levels of Nrf2 and interleukin-10 (IL-10) were observed in rectum tissues. Increased fibrous tissue proliferation, vascularization and inflammatory cell infiltration were described in the colitis group. Significant improvement was observed in MSCs treated group histopathologically. Increased immunopositivity of TNF-α, vascular endothelial growth factor (VEGF) and CD68 markers was observed in the colitis group cells, and decreased level of this positivity was observed in MSCs treated group.

Conclusions:

Biochemical, histopathological and immunohistochemical results strongly support the ameliorative effect of MSCs against acetic induced colitis model via Nrf2/HO-1 pathway in rats.

Key words
Inflammation; Acetic Acid; Mesenchymal Stem Cells; NF-E2-Related Factor 2; Vascular Endothelial Growth Factor A

Biochemical parameters	Control group	Colitis and % 0.9 NaCl (saline) given group	Colitis and MSCgiven group
Plasma TNF-α level (pg/mL)	16.7 ± 1.1	63.9 ± 2.7^* * p < 0.05 significant difference from normal groups;	38.3 ± 5.4^## ## p < 0.001 significant difference from colitis and MSCs treated groups; MSC: mesenchymal stem cells; TNF-α: tumor necrosis factor-α; PTX-3: pentraxin-3; MDA: malondialdehyde; IL: interleukine.
Plasma PTX-3 level (ng/mL)	0.74 ± 0.06	3.1 ± 0.15^ p < 0.001 significant difference from normal groups;	1.6 ± 0.09^## ## p < 0.001 significant difference from colitis and MSCs treated groups; MSC: mesenchymal stem cells; TNF-α: tumor necrosis factor-α; PTX-3: pentraxin-3; MDA: malondialdehyde; IL: interleukine.
Plasma MDA level (nM)	58.5 ± 9.3	102.6 ± 12.6^ p < 0.001 significant difference from normal groups;	98.9 ± 7.5^# # p < 0.01 significant difference from colitis and MSCs treated groups;
Rectum TNF-α level (pg/mg tissue)	61.1 ± 4.2	113.8 ± 9.2^* * p < 0.05 significant difference from normal groups;	77.4 ± 6.6^# # p < 0.01 significant difference from colitis and MSCs treated groups;
Rectum Nrf-2 level (pg/mg protein)	27.6 ± 3.5	10.3 ± 2.06^ p < 0.001 significant difference from normal groups;	19.2 ± 1.5^# # p < 0.01 significant difference from colitis and MSCs treated groups;
Rectum IL-10 level (pg/mg protein)	1.08 ± 0.03	0.65 ± 0.02^ p < 0.001 significant difference from normal groups;	0.84 ± 0.02^# # p < 0.01 significant difference from colitis and MSCs treated groups;

Groups	H&E results
Control group	0.00 ± 0.00
Colitis and % 0.9 NaCl (saline) given group	3.40 ± 0.69^ p < 0.001 significant difference from normal groups;
Colitis and MSC given group	2.10 ± 1.10^# ## p < 0.001 significant difference from colitis and MSCs treated groups; MSC: mesenchymal stem cells; H&E: hematoxylin and eosin.

Groups	TNF	VEGF	CD68
Control group	0.70 ± 0.48	0.90 ± 0.32	0.00 ± 0.00
Colitis and % 0.9 NaCl (saline) given group	2.40 ± 0.70^ p < 0.001 significant difference from normal groups;	2.50 ± 0.71^ p < 0.001 significant difference from normal groups;	1.30 ± 0.67^ p < 0.001 significant difference from normal groups;
Colitis and MSC given group	1.10 ± 0.57^## ## p < 0.001 significant difference from colitis and MSCs treated groups.	1.50 ± 0.85^## ## p < 0.001 significant difference from colitis and MSCs treated groups.	0.70 ± 0.67^## ## p < 0.001 significant difference from colitis and MSCs treated groups.

Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia https://actacirbras.com.br/ - São Paulo - SP - Brazil
E-mail: actacirbras@gmail.com

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[1] *Corresponding author: fbozkurt@gmail.com | (90 53) 18506172