The effect of microencapsulated watermelon rind (Citrullus lanatus) and beetroot (Beta vulgaris L.) ingestion on ischemia/reperfusion-induced endothelial dysfunction: a randomised clinical trial.

Endothelial dysfunction is commonly associated with a cardiovascular event, such as myocardial infarction. Myocardial infarction is marked by an ischemia/reperfusion (IR) phenomenon associated with endothelial dysfunction, contributing even more to future cardiovascular events. Although the supplementation with L-citrulline and nitrate from watermelon and beetroot have been used to improve vascular function, the effect of microencapsulated watermelon rind (WR) or its co-ingestion with beetroot (WR + B) on endothelial IR injury has not been addressed. Therefore, this study aimed to investigate the effect of a single dose of WR and WR + B on IR-induced macro-and microvascular dysfunction. In a randomized, crossover, placebo-controlled study, 12 volunteers underwent macro (flow-mediated dilation) and microvascular (muscle oxygen saturation) assessment and blood collection (to measure L-citrulline, L-arginine, nitrate and nitrite) before and after 20 min of blood occlusion in WR, WR + B and placebo conditions. Prolonged ischemia induced endothelial dysfunction in the macro but not in the microvasculature. The WR and WR + B supplementation significantly restored FMD after IR injury compared to the placebo (p < 0.05). However, there was no significant difference between WR and WR + B in the macrovascular function (p > 0.05). Plasma L-citrulline, L-arginine, nitrate, and nitrite significantly increased (p > 0.05) after WR and WR + B supplementation compared to the placebo. A single dose of WR and WR + B effectively minimizes IR-induced macrovascular endothelial dysfunction in healthy individuals. Beetroot co-ingestion with watermelon did not provide an additional effect of endothelial dysfunction induced by IR (NCT04781595, March 4, 2021).

Ferroptosis: A Double-Edged Sword in Gastrointestinal Disease.

Ferroptosis is a novel form of regulated cell death (RCD) that is typically accompanied by iron accumulation and lipid peroxidation. In contrast to apoptosis, autophagy, and necroptosis, ferroptosis has unique biological processes and pathophysiological characteristics. Since it was first proposed in 2012, ferroptosis has attracted attention worldwide. Ferroptosis is involved in the progression of multiple diseases and could be a novel therapeutic target in the future. Recently, tremendous progress has been made regarding ferroptosis and gastrointestinal diseases, including intestinal ischemia/reperfusion (I/R) injury, inflammatory bowel disease (IBD), gastric cancer (GC), and colorectal cancer (CRC). In this review, we summarize the recent progress on ferroptosis and its interaction with gastrointestinal diseases. Understanding the role of ferroptosis in gastrointestinal disease pathogenesis could provide novel therapeutic targets for clinical treatment.

Dietary intake of n-3 polyunsaturated fatty acids alters the lipid mediator profile of the kidney but does not attenuate renal insufficiency.

The efficacy of n-3 polyunsaturated fatty acids (PUFAs) in improving outcomes in a renal ischemia-reperfusion injury (IRI) model has previously been reported. However, the underlying mechanisms remain poorly understood and few reports demonstrate how dietary n-3 PUFAs influence the composition of membrane phospholipids in the kidney. Additionally, it has not been elucidated whether perilla oil (PO), which is mainly composed of the n-3 alpha-linolenic acid, mitigates renal IRI. In this study, we investigated the effect of dietary n-3 PUFAs (PO), compared with an n-6 PUFA-rich soybean oil (SO) diet, on IRI-induced renal insufficiency in a rat model. Levels of membrane phospholipids containing n-3 PUFAs were higher in the kidney of PO-rich diet-fed rats than the SO-rich diet-fed rats. Levels of blood urea nitrogen and serum creatinine were significantly higher in the ischemia-reperfusion group than the sham group under both dietary conditions. However, no significant differences were observed in blood urea nitrogen, serum creatinine, or histological damage between PO-rich diet-fed rats and SO-rich diet-fed rats. In the kidney of PO-rich diet-fed rats, levels of arachidonic acid and arachidonic acid-derived pro-inflammatory lipid mediators were lower than SO-rich diet-fed rats. Eicosapentaenoic acid and eicosapentaenoic acid-derived lipid mediators were significantly higher in the kidney of PO-rich than SO-rich diet-fed rats. These results suggest that dietary n-3 PUFAs alter the fatty acid composition of membrane phospholipids and lipid mediators in the kidney; however, this does not attenuate renal insufficiency or histological damage in a renal IRI model.

Consumption of Anacardium Occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO-1 and NF-kB Pathways.

Ischemia/reperfusion injury is a severe disorder associated with a high mortality. Several antioxidant and pharmacological properties of cashew nuts (Anacardium occidentale L.) and its metabolites from different countries have recently been described. It is a medicinal plant with important therapeutic effects. This study aimed to verify the effect of an oral administration of cashew nuts in a rat model of ischemia/reperfusion (I/R). Adult male rats were subjected to intestinal I/R injury by clamping the superior mesenteric artery for 30 min and then allowing animals to 1 h of reperfusion. Rats subjected to I/R of the gut showed a significant increase in different biochemical markers. In particular, we evaluated lipid peroxidation, tissue myeloperoxidase activity, protein carbonyl content, reactive oxygen species generation and decreased antioxidant enzyme activities. Western blot analysis showed the activation of the NRF2 and NF-kB pathways. Increased immunoreactivity to nitrotyrosine, PARP, P-selectin, and ICAM-1 was observed in the ileum of rats subjected to I/R. Administration of cashew nuts (100 mg/kg) significantly reduced the mortality rate, the fall in arterial blood pressure, and oxidative stress and restored the antioxidant enzyme activities by a mechanism involving both NRF2 and NF-kB pathways. Cashew nuts treatments reduced cytokines plasma levels, nitrotyrosine, and PARP expression as well as adhesion molecules expressions. Additionally, cashew nuts decreased the intestinal barrier dysfunction and mucosal damage, the translocation of toxins and bacteria, which leads to systemic inflammation and associated organs injuries in particular of liver and kidney. Our study demonstrates that cashew nuts administration exerts antioxidant and pharmacological protective effects in superior mesenteric artery occlusion-reperfusion shock.

Dietary methionine restriction attenuates renal ischaemia/reperfusion-induced myocardial injury by activating the CSE/H2S/ERS pathway in diabetic mice.

Methionine restrictive diet may alleviate ischaemia/reperfusion (I/R)-induced myocardial injury, but its underlying mechanism remains unclear. HE staining was performed to evaluate the myocardial injury caused by I/R and the effect of methionine-restricted diet (MRD) in I/R mice. IHC and Western blot were carried out to analyse the expression of CSE, CHOP and active caspase3 in I/R mice and hypoxia/reoxygenation (H/R) cells. TUNEL assay and flow cytometry were used to assess the apoptotic status of I/R mice and H/R cells. MTT was performed to analyse the proliferation of H/R cells. H2S assay was used to evaluate the concentration of H2S in the myocardial tissues and peripheral blood of I/R mice. I/R-induced mediated myocardial injury and apoptosis were partially reversed by methionine-restricted diet (MRD) via the down-regulation of CSE expression and up-regulation of CHOP and active caspase3 expression. The decreased H2S concentration in myocardial tissues and peripheral blood of I/R mice was increased by MRD. Accordingly, in a cellular model of I/R injury established with H9C2 cells, cell proliferation was inhibited, cell apoptosis was increased, and the expressions of CSE, CHOP and active caspase3 were dysregulated, whereas NaHS treatment alleviated the effect of I/R injury in H9C2 cells in a dose-dependent manner. This study provided a deep insight into the mechanism underlying the role of MRD in I/R-induced myocardial injury.

Effects of Dioscorea polystachya 'yam gruel' on the cognitive function of diabetic rats with focal cerebral ischemia-reperfusion injury via the gut-brain axis.

Focal cerebral ischemia-reperfusion injury is closely related to hyperglycemia and gut microbiota imbalance, while gut microbiota contributes to the regulation of brain function through the gut-brain axis. Previous studies in patients with diabetes have found that 'yam gruel' is a classic medicated diet made from Dioscorea polystachya, increases the content of Bifidobacterium, regulates oxidative stress, and reduces fasting blood glucose levels. The research reported here investigated the effects of 'yam gruel' on the cognitive function of streptozotocin-induced diabetic rats with focal cerebral ischemia-reperfusion injury and explored the mechanism underlying the role of the gut-brain axis in this process. 'Yam gruel' was shown to improve cognitive function as indicated by increased relative content of probiotic bacteria, and short-chain fatty acids in the intestinal tract and cerebral cortex reduced oxidative stress and inflammatory response and promotion of the expression of neurotransmitters and brain-derived neurotrophic factor. Thus, it is concluded that 'yam gruel' has a protective effect on cognitive function via a mechanism related to the gut-brain axis.

Combined docosahexaenoic acid and thyroid hormone supplementation as a protocol supporting energy supply to precondition and afford protection against metabolic stress situations.

Liver preconditioning (PC) refers to the development of an enhanced tolerance to injuring stimuli. For example, the protection from ischemia-reperfusion (IR) in the liver that is obtained by previous maneuvers triggering beneficial molecular and functional changes. Recently, we have assessed the PC effects of thyroid hormone (T3; single dose of 0.1 mg/kg) and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs; daily doses of 450 mg/kg for 7 days) that abrogate IR injury to the liver. This feature is also achieved by a combined T3 and the n-3 LCPUFA docosahexaenoic acid (DHA) using a reduced period of supplementation of the FA (daily doses of 300 mg/kg for 3 days) and half of the T3 dosage (0.05 mg/kg). T3 -dependent protective mechanisms include (i) the reactive oxygen species (ROS)-dependent activation of transcription factors nuclear factor-κB (NF-κB), AP-1, signal transducer and activator of transcription 3, and nuclear factor erythroid-2-related factor 2 (Nrf2) upregulating the expression of protective proteins. (ii) ROS-induced endoplasmic reticulum stress affording proper protein folding. (iii) The autophagy response to produce FAs for oxidation and ATP supply and amino acids for protein synthesis. (iv) Downregulation of inflammasome nucleotide-bonding oligomerization domain leucine-rich repeat containing family pyrin containing 3 and interleukin-1ß expression to prevent inflammation. N-3 LCPUFAs induce antioxidant responses due to Nrf2 upregulation, with inflammation resolution being related to production of oxidation products and NF-κB downregulation. Energy supply to achieve liver PC is met by the combined DHA plus T3 protocol through upregulation of AMPK coupled to peroxisome proliferator-activated receptor-γ coactivator 1α signaling. In conclusion, DHA plus T3 coadministration favors hepatic bioenergetics and lipid homeostasis that is of crucial importance in acute and clinical conditions such as IR, which may be extended to long-term or chronic situations including steatosis in obesity and diabetes. © 2019 IUBMB Life, 71(9):1211-1220, 2019.

Fasting reduces oxidative stress, mitochondrial dysfunction and fibrosis induced by renal ischemia-reperfusion injury.

Food deprivation protects against ischemia-reperfusion (IR) injury through unknown mechanisms. In an experimental rat model of acute IR injury, we found that preoperative fasting for 3 days protects rats from tubular damage and renal functional decline by increasing antioxidant protection independently of the NF-E2-related factor 2 (Nrf2), and by maintaining mitochondrial morphology and function. In addition, further analysis revealed that fasting protects against tubulointerstitial fibrosis. In summary, our results point out to fasting as a robust nutritional intervention to limit oxidative stress and mitochondrial dysfunction in early acute kidney injury and also to promote long-term protection against fibrosis.

l-Homocarnosine attenuates inflammation in cerebral ischemia-reperfusion injury through inhibition of nod-like receptor protein 3 inflammasome.

We investigated the therapeutic effects of l-homocarnosine against inflammation in a rat model of cerebral ischemia-reperfusion injury. Rats were grouped into control, middle cerebral artery occlusion (MCAO), 0.5 mM l-homocarnosine + MCAO, and 1 mM l-homocarnosine + MCAO treatment groups. Superoxide dismutase (SOD), glutathione peroxidase (Gpx), catalase, lipid peroxidation, and reduced glutathione (GSH) levels were measured. Neurological scores were assessed, and histopathology, scanning electron microscopy (SEM), and fluorescence microscopy analyses were conducted. The mRNA expression levels of nod-like receptor protein 3 (NLRP3), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) and protein expression levels of NLRP3 were assessed. l-Homocarnosine supplementation substantially increased SOD, catalase, Gpx, and GSH levels, whereas it reduced the levels of lipid peroxidation relative to MCAO rats. l-Homocarnosine significantly reduced the infarct area and neurological deficit score, as well as histopathological alteration, apoptosis, and necrosis in brain tissue. The mRNA expression levels of NLRP3, TNF-α, and IL-6 were increased in MCAO rats, whereas l-homocarnosine supplementation reduced mRNA expression by >40%, and NLRP3 protein expression was reduced by >30% in 1 mM l-homocarnosine-treated MCAO rats. We propose that l-homocarnosine exerts a protective effect in cerebral ischemia-reperfusion injury-induced rats by downregulating NLRP3 expression.

Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p≤0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

Supplementation with different teas from Camellia sinensis prevents memory deficits and hippocampus oxidative stress in ischemia-reperfusion.

Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis. Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis.

Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation.

Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms.

Partial Enteral Nutrition Mitigated Ischemia/Reperfusion-Induced Damage of Rat Small Intestinal Barrier.

BACKGROUND AND AIMS: This study was designed to investigate a relatively optimum dose of partial enteral nutrition (PEN) which effectively attenuates intestinal barrier dysfunction initiated by ischemia/reperfusion injury (IRI). METHODS: In experiment 1, 60 male Sprague-Dawley (SD) rats were subjected to intestinal IRI and assigned to six groups according to the different proportion of EN administrations: namely total parenteral nutrition (TPN or 0%EN), 10%EN, 20%EN, 40%EN, 60%EN, and total enteral nutrition (TEN or 100%) groups, the deficits of intraluminal calorie were supplemented by PN. In experiment 2, 50 male SD rats were subjected to intestinal IRI and divided into five groups based on the results of experiment 1: TPN, TEN, 20%EN, TPN plus pretreatment with NF-κB antagonist 30 min before IRI (TPN+PDTC), and TPN plus pretreatment with HIF-1α antagonist 30 min before IRI (TPN+YC-1) groups. RESULTS: In experiment 1, previous IRI combined with subsequent EN shortage disrupted the structure of intestinal epithelial cell and tight junctions (TJs). While 20% dose of EN had an obviously protective effect on these detrimental consequences. In experiment 2, compared with TPN only, 20%EN exerted a significant protection of barrier function of intestinal epithelium. Analogous results were observed when TPN combined with specific NF-κB/HIF-1α inhibitors (PDTC and YC-1). Meanwhile, the expression of NF-κB/HIF-1α had a similar trend among the groups. CONCLUSIONS: Our findings indicate that 20%EN is the minimally effective dosage of EN which promotes the recovery of intestinal barrier function after IRI in a rat model. Furthermore, we discreetly speculate that this benefit is, at least partly, related to NF-κB/HIF-1α pathway expression.

Selenium Pretreatment for Mitigation of Ischemia/Reperfusion Injury in Cardiovascular Surgery: Influence on Acute Organ Damage and Inflammatory Response.

Ischemia/reperfusion injury (IRI) contributes to morbidity and mortality after cardiovascular surgery requiring cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Multi-organ damage is associated with substantial decreases of blood selenium (Se) levels in patients undergoing cardiac surgery with CPB. We compared the influence of a dietary surplus of Se and pretreatment with ebselen, a mimic of the selenoenzyme glutathione peroxidase, on IRI-induced tissue damage and inflammation. Male Wistar rats were fed either a Se-adequate diet containing 0.3 ppm Se or supplemented with 1 ppm Se (as sodium selenite) for 5 weeks. Two other groups of Se-adequate rats received intraperitoneal injection of ebselen (30 mg/kg) or DMSO (solvent control) before surgery. The animals were connected to a heart-lung-machine and underwent 45 min of global ischemia during circulatory arrest at 16 °C, followed by re-warming and reperfusion. Selenite and ebselen suppressed IRI-induced leukocytosis and the increase in plasma levels of tissue damage markers (AST, ALT, LDH, troponin) during surgery but did not prevent the induction of proinflammatory cytokines (IL-6, TNF-α). Both Se compounds affected phosphorylation and expression of proteins related to stress response and inflammation: Ebselen increased phosphorylation of STAT3 transcription factor in the heart and decreased phosphorylation of ERK1/2 MAP kinases in the lungs. Selenite decreased ERK1/2 phosphorylation and HSP-70 expression in the heart. Pretreatment with selenite or ebselen protected against acute IRI-induced tissue damage during CPB and DHCA. Potential implications of their different actions with regard to molecular stress markers on the recovery after surgery represent promising targets for further investigation.

Calorie restriction attenuates cerebral ischemic injury via increasing SIRT1 synthesis in the rat.

Caloric restriction (CR) has been shown to have several health benefits and provides protection against type 2 diabetes, neurodegenerative and cerebral vascular diseases. It reduces the brain infarct size and promotes neurological functional recovery after cerebral ischemia. Sirtuin 1 (SIRT1) plays an important role in the biological effects induced by CR. This study investigated the role of SIRT1 in ischemic tolerance in the brain induced by CR. Sprague drawly rats were divided into two groups based on food intake. Ad libitum (AL) group was fed with normal diet while the CR group received 60% calories compared to AL. All animals were subjected to a middle cerebral artery occlusion for 90 min. Results showed the neurological function score of CR group was higher and the brain infarct volume was markedly reduced in CR group compared to AL group at 24h after reperfusion (p < 0.05). CR increased the synthesis of SIRT1 significantly (p < 0.05), and ameliorated the down regulation of SIRT1 expression at 6 and 12h after middle cerebral artery occlusion (p < 0.05, p < 0 .01, respectively). Knockdown of SIRT1 by siRNA in vivo reversed the neuroprotective effect of CR. From this study, we deduce that CR induces brain ischemic tolerance on rats via increasing the synthesis of SIRT1.

Effects of kefir on ischemia-reperfusion injury.

OBJECTIVE: We aimed to investigate the effect of kefir on Ischemia-Reperfusion (I/R) injury on rats. MATERIALS AND METHODS: 24 male Sprague-Dawley rats between 250-350 g were selected. Rats were divided into three groups, and there were eight rats in each group. Rats were fed for 60 days. All of the rats were fed with the same diet for the first 30 days. In the second thirty days, kefir [10 cc/kg/day body weight (2 x 109 cfu/kg/day)] was added to the diet of the study group by gavage method. In all groups, lung and kidney tissues were removed after the procedure and rats were sacrificed. The biochemical and histopathological changes were observed in the lung and kidney within the samples. Serum urea, creatinine and tumor necrosis factor (TNF-α) were determined. RESULTS: Kefir + I/R groups was compared with I/R groups, a significant decrease (p < 0.05) was seen in Lipid peroxidation (MDA) levels of lung and renal tissues. Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSH-Px) activities of lung and kidney tissues decreased in I/R groups (p < 0.05). The enzyme activities in Kefir + I/R groups of renal tissues were significantly (p < 0.05) higher than I/R, not significantly different in lung tissues (p < 0.05). Kefir reduced the levels of serum urea, creatinine and TNF-α significantly. CONCLUSIONS:   This would be useful in this model against ischemia/reperfusion, and shows the protective effect of kefir in tissue and serum functions.

n-3 PUFA induce microvascular protective changes during ischemia/reperfusion.

Ischemia/reperfusion (I/R) injury can occur in consequence of myocardial infarction, stroke and multiple organ failure, the most prevalent cause of death in critically ill patients. I/R injury encompass impairment of endothelial dependent relaxation, increase in macromolecular permeability and leukocyte-endothelium interactions. Polyunsaturated fatty acids (n-3 PUFA), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) found in fish oil have several anti-inflammatory properties and their potential benefits against I/R injury were investigated using the hamster cheek pouch preparation before and after ischemia. Before the experiments, hamsters were treated orally with saline, olive oil, fish oil and triacylglycerol (TAG) and ethyl ester (EE) forms of EPA and DHA at different daily doses for 14 days. Fish oil restored the arteriolar diameter to pre ischemic values during reperfusion. At onset and during reperfusion, Fish oil and DHA TAG significantly reduced the number of rolling leukocytes compared to saline and olive oil treatments. Fish oil, EPA TAG and DHA TAG significantly prevented the rise on leukocyte adhesion compared to saline. Fish oil (44.83 ± 3.02 leaks/cm(2)), EPA TAG (31.67 ± 2.65 leaks/cm(2)), DHA TAG (41.14 ± 3.63 leaks/cm(2)), and EPA EE (30.63 ± 2.25 leaks/cm(2)), but not DHA EE (73.17 ± 2.82 leaks/cm(2)) prevented the increase in macromolecular permeability compared to saline and olive oil (134.80 ± 1.49 and 121.00 ± 4.93 leaks/cm(2), respectively). On the basis of our findings, we may conclude that consumption of n-3 polyunsaturated fatty acids, especially in the triacylglycerol form, could be a promising therapy to prevent microvascular damage induced by ischemia/reperfusion and its consequent clinical sequelae.

Temporal changes in hepatic antioxidant enzyme activities after ischemia and reperfusion in a rat liver ischemia model: effect of dietary fish oil.

This study investigated the hypothesis that administration of tilapia fish oil diet would attenuate warm liver ischemia/reperfusion injury (IRI) and whether fish oil modulates prooxidant/antioxidant status. Male Wistar rats were subjected to 30 min of approximately 70% hepatic ischemia followed by 1, 12, and 24 h reperfusion. Rats were randomly divided into three groups: sham-operated group (SO), control-warm hepatic ischemia (WI) group, and Oil-WI group given tilapia oil for 3 weeks followed by liver IRI. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured in the plasma. Levels of thiobarbituric acid reactive substances (TBARS) and antioxidant enzymes as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured in liver fractions. In the sham group, there was no enzymatic or histological change. I/R caused significant increase in serum AST, ALT, and tissue TBARS levels. As compared to the control group, animals treated with tilapia oil experienced a significant decrease (p < 0.05) in AST and ALT levels in reperfusion periods. Tissue TBARS levels in Oil-WI group were significantly (p < 0.05) reduced as compared to control group at 60 min after reperfusion. After ischemia, 1, 12, and 24 h of reperfusion, CAT, SOD, and GPx values were the lowest in the Oil-WI group and highest in the control group and were statistically significant (p < 0.05). Histological analysis also revealed that fish oil provided some protection compared with the control group. Tilapia oil exerts a protective effect during the early phase of reperfusion, and it modulates prooxidant/antioxidant status of rat liver subjected to warm IRI.

The TSC complex is required for the benefits of dietary protein restriction on stress resistance in vivo.

Protein restriction (PR) is important for the benefits of dietary restriction on longevity and stress resistance, but relevant nutrient sensors and downstream effectors in mammals remain poorly defined. We used PR-mediated protection from hepatic ischemia reperfusion injury to probe genetic requirements for the evolutionarily conserved nutrient sensors GCN2 and mTORC1 in stress resistance. One week of PR reduced free amino acids and circulating growth factors, activating GCN2 and mTORC1 repressor tuberous sclerosis complex (TSC). However, although GCN2 was dispensable for PR-induced protection, hepatic TSC1 was required. PR improved hepatic insulin sensitivity in a TSC1-dependent manner prior to ischemia, facilitating increased prosurvival signaling and reduced apoptosis after reperfusion. These benefits were partially abrogated by pharmacological PI3K inhibition or genetic deletion of the insulin receptor in hepatocytes. In conclusion, improved insulin sensitivity upon short-term PR required TSC1, facilitated increased prosurvival signaling after injury, and contributed partially to PR-mediated resistance to clinically relevant ischemia reperfusion injury.

Benefits of short-term dietary restriction in mammals.

Dietary or calorie restriction (DR, CR), defined as reduced food intake without malnutrition, imparts many benefits in model organisms. Extended longevity is the most popularized benefit but the least clinically relevant due to the requirement for long-term food restriction. DR also promotes stress resistance and metabolic fitness. Emerging data in experimental models and in humans indicate that these benefits occur rapidly upon initiation of DR, suggesting potential clinical relevance. Here we review data on the ability of short-term DR to induce beneficial effects on clinically relevant endpoints including surgical stress, inflammation, chemotherapy and insulin resistance. The encouraging results obtained in these preclinical and clinical studies, and the general lack of mechanistic understanding, both strongly suggest the need for further research in this emerging area.