Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats

Ozyigit, Filiz; Deger, Ayse Nur; Kocak, Fatma Emel; Ekici, Mehmet Fatih; Simsek, Hasan; Arık, Ozlem

doi:10.1590/acb391124

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Acta Cirúrgica Brasileira

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Original Article • Acta Bras Cir 39 • 2024 • https://doi.org/10.1590/acb391124 copy

Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Purpose:

This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion.

Methods:

Fifty male Sprague Dawley rats (250–300 g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100 mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45 minutes ischemia and 60 minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acid–Schiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined.

Results:

Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue.

Conclusions:

Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.

Key words
Hesperidin; Ischemia; Reperfusion; Wounds and Injuries

Parameters group 1 (mean ± SD) (Control) (n = 10)	Group 2 (Sham)(n = 10)	Group 3 (Ischemia) (n = 10)	Group 4 (I/R)(n = 10)	Group 5 (H + IR) (n = 10)	P-value
TT (μmol/mg 22.5 ± 3.34)	21.5 ± 4.07	10.31 ± 2.33^ab	7.08 ± 1.15^abc	11.46 ± 2.83^abd	< 0.0001
TAS(mmol Trolox 0.11 ± 0.013 Eq/mg protein)	0.11 ± 0.019	0.072 ± 0.013^ab	0.042 ± 0.01^abc	0.076 ± 0.015^abd	< 0.0001
TOS 0.022 ± 0.015(μmol H₂O₂ Eq/mg protein)	0.027 ± 0.013	0.058 ± 0.014^ab	0.078 ± 0.015^ab	0.049 ± 0.019^abd	< 0.0001
OSI (Arbitrary 0.02 ± 0.013 Unit)	0.024 ± 0.01	0.083 ± 0.021^ab	0.19 ± 0.031^abc	0.067 ± 0.021^abd	< 0.0001
SOD (U/mg 1.39 ± 0.22 protein)	1.25 ± 0.15	0.82 ± 0.10^ab	0.53 ± 0.14^abc	1.07 ± 0.26^acd	< 0.0001
GSH-PX (U/mg 7.69 ± 1.73 protein)	7.34 ± 1.34	4.02 ± 1.12^ab	2.60 ± 0.65^abc	4.58 ± 1.42^abd	< 0.0001
MDA (μM/mg 0.23 ± 0.06 protein)	0.24 ± 0.08	0.70 ± 0.20^ab	0.76 ± 0.14^ab	0.48 ± 0.13^abcd	< 0.0001

Parameters (mean ± SD)		Group 1	Group 2	Group 3	Group 4	Group 5	P-value
Parameters (mean ± SD)		(Control)	(Sham)	(Ischemia)	(I/R)	(H + IR)	P-value
	PAS	0.0 (0.0–0.0)	0.0 (0.0–0.0)	2.0 (1.0–2.0)^ab	2.0 (2.0–2.3)^ab	1.0 (1.0–1.3)^abd	< 0.0001
Gastric damage		(n = 10) 0.0 (0.0–0.0)	(n = 10) 0.0 (0.0–0.0)	(n = 10) 2.0 (1.0–2.0)^ab	(n = 10) 2.0 (2.0–2.0)^ab	(n = 10) 1.0 (1.0–1.0)^abcd	< 0.0001
(H&E)
	Apoptotic index	2.2 ± 1.2	2.3 ± 1.0	11.1 ± 3.5^ab	14.8 ± 3.9^ab	6.1 ± 1.2^abcd	< 0.0001
	HIF-1α	8.8 ± 3.4	7.9 ± 4.2	14.8 ± 5.8^b	16.9 ± 6.3^ab	9.2 ±. 5.6^d	< 0.0001
	PCNA	41.3 ± 14.2	33.0 ± 8.1	19.9 ± 2.1^ab	15.7 ± 5.3^ab	31.0 ± 5.8^cd	< 0.0001

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: fozyigit@bandirma.edu.tr