Increased Antioxidant Capacity of Serum Did Not Prevent Lipid Peroxidation in the Intermittent Ischemia-Reperfusion of Rat Small Intestine

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

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The nitric oxide donor molsidomine prevents ischemia/reperfusion injury of the adult rat small intestine

Pediatric Surgery International ◽

10.1007/s00383-002-0746-y ◽

2003 ◽

Vol 19 (4) ◽

pp. 305-308 ◽

Cited By ~ 4

Author(s):

Hayrettin Öztürk ◽

Mustafa Aldemir ◽

Ali İhsan Dokucu ◽

Yusuf Yağmur ◽

Nihal Kilinç ◽

...

Keyword(s):

Nitric Oxide ◽

Small Intestine ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Nitric Oxide Donor ◽

Rat Small Intestine ◽

Adult Rat

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Effect of Aminoguanidine on Ischemia/Reperfusion Injury in Rat Small Intestine

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.34.1737 ◽

2011 ◽

Vol 34 (11) ◽

pp. 1737-1743 ◽

Cited By ~ 9

Author(s):

Yusuke Takizawa ◽

Takuya Kitazato ◽

Haruka Ishizaka ◽

Naomi Kamiya ◽

Mikio Tomita ◽

...

Keyword(s):

Small Intestine ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Rat Small Intestine

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Involvement of hyaluronan in the adaptive changes of the rat small intestine neuromuscular function after ischemia/reperfusion injury

Scientific Reports ◽

10.1038/s41598-020-67876-9 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Michela Bistoletti ◽

Annalisa Bosi ◽

Ilaria Caon ◽

Anna Maria Chiaravalli ◽

Paola Moretto ◽

...

Keyword(s):

Small Intestine ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Neuromuscular Function ◽

Rat Small Intestine ◽

Adaptive Changes

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Gene expression in human small intestinal mucosa in vivo is mediated by iron-induced oxidative stress

Physiological Genomics ◽

10.1152/physiolgenomics.00114.2005 ◽

2006 ◽

Vol 25 (2) ◽

pp. 242-249 ◽

Cited By ~ 7

Author(s):

Freddy J. Troost ◽

Robert-Jan M. Brummer ◽

Guido R. M. M. Haenen ◽

Aalt Bast ◽

Rachel I. van Haaften ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Lipid Peroxidation ◽

Small Intestine ◽

Antioxidant Capacity ◽

Intestinal Mucosa ◽

Thiobarbituric Acid ◽

Thiobarbituric Acid Reactive Substances ◽

Oxidative Challenge ◽

Gene Reporters

Iron-induced oxidative stress in the small intestine may alter gene expression in the intestinal mucosa. The present study aimed to determine which genes are mediated by an iron-induced oxidative challenge in the human small intestine. Eight healthy volunteers [22 yr(SD2)] were tested on two separate occasions in a randomized crossover design. After duodenal tissue sampling by gastroduodenoscopy, a perfusion catheter was inserted orogastrically to perfuse a 40-cm segment of the proximal small intestine with saline and, subsequently, with either 80 or 400 mg of iron as ferrous gluconate. After the intestinal perfusion, a second duodenal tissue sample was obtained. Thiobarbituric acid-reactive substances, an indicator of lipid peroxidation, in intestinal fluid samples increased significantly and dose dependently at 30 min after the start of perfusion with 80 or 400 mg of iron, respectively ( P < 0.001). During the perfusion with 400 mg of iron, the increase in thiobarbituric acid-reactive substances was accompanied by a significant, momentary rise in trolox equivalent antioxidant capacity, an indicator of total antioxidant capacity ( P < 0.05). The expression of 89 gene reporters was significantly altered by both iron interventions. Functional mapping showed that both iron dosages mediated six distinct processes. Three of those processes involved G-protein receptor coupled pathways. The other processes were associated with cell cycle, complement activation, and calcium channels. Iron administration in the small intestine induced dose-dependent lipid peroxidation and a momentary antioxidant response in the lumen, mediated the expression of at least 89 individual gene reporters, and affected at least six biological processes.

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