Stimulation of the calcium-sensing receptor induces relaxations of rat mesenteric arteries by endothelium-dependent and -independent pathways via BKCa and KATP channels.

Stimulation of the calcium-sensing receptor (CaSR) induces both vasoconstrictions and vasorelaxations but underlying cellular processes remain unclear. This study investigates expression and effect of stimulating the CaSR by increasing external Ca2+ concentration ([Ca2+ ]o ) on contractility of rat mesenteric arteries. Immunofluorescence studies showed expression of the CaSR in perivascular nerves, vascular smooth muscle cells (VSMCs), and vascular endothelium cells. Using wire myography, increasing [Ca2+ ]o from 1 to 10 mM induced vasorelaxations which were inhibited by the calcilytic Calhex-231 and partially dependent on a functional endothelium. [Ca2+ ]o -induced vasorelaxations were reduced by endothelial NO synthase (eNOS, L-NAME) and large conductance Ca2+ -activated K+ channels (BKCa , iberiotoxin), with their inhibitory action requiring a functional endothelium. [Ca2+ ]o -induced vasorelaxations were also markedly inhibited by an ATP-dependent K+ channel (KATP ) blocker (PNU37883), which did not require a functional endothelium to produce its inhibitory action. Inhibitor studies also suggested contributory roles for inward rectifying K+ channels (Kir ), Kv7 channels, and small conductance Ca2+ -activated K+ channels (SKCa ) on [Ca2+ ]o -induced vasorelaxations. These findings indicate that stimulation of the CaSR mediates vasorelaxations involving multiple pathways, including an endothelium-dependent pathway involving NO production and activation of BKCa channels and an endothelium-independent pathway involving stimulation of KATP channels.

Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries.

OBJECTIVE: This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA). METHODS: Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography. RESULTS: High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619. CONCLUSION: These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.

Melatonin prevents overproduction of reactive oxygen species and vascular dysfunction induced by cyclophosphamide.

AIMS: Overproduction of reactive oxygen species (ROS) is a pathologic hallmark of cyclophosphamide toxicity. For this reason, antioxidant compounds emerge as promising tools for preventing tissue damage induced by cyclophosphamide. We hypothesized that melatonin would display cytoprotective action in the vasculature by preventing cyclophosphamide-induced oxidative stress. MATERIALS AND METHODS: Male C57BL/6 mice (22-25 g) were injected with a single dose of cyclophosphamide (300 mg/kg; i.p.). Mice were pretreated or not with melatonin (10 mg/kg/day, i.p.), given during 4 days before cyclophosphamide injection. Functional (vascular reactivity) and oxidative/inflammatory patterns were evaluated at 24 h in resistance arteries. The antioxidant action of melatonin was assessed in vitro in cultured vascular smooth muscle cells (VSMCs) of mesenteric arteries. KEY FINDINGS: Cyclophosphamide induced ROS generation in both mesenteric arterial bed (MAB) and cultured VSMCs, and this was normalized by melatonin. Cyclophosphamide-induced ROS generation and lipoperoxidation in the bladder and kidney was also prevented by melatonin. Increased levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were detected in the MAB of cyclophosphamide-treated mice, all of which were prevented by melatonin. Functional assays using second-order mesenteric arteries of cyclophosphamide-treated mice revealed a decrease in vascular contractility. Melatonin prevented vascular hypocontractility in the cyclophosphamide group. Melatonin partially prevented the decrease in myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities in the MAB of the cyclophosphamide group. SIGNIFICANCE: Melatonin may constitute a novel and promising therapeutic approach for management of the toxic effects induced by cyclophosphamide in the vasculature.

Acute, pro-contractile effects of prorenin on rat mesenteric arteries.

Prorenin and the prorenin receptor ((P)RR) are important, yet controversial, members of the renin-angiotensin-aldosterone system. The ((P)RR) is expressed throughout the body, including the vasculature, however, the direct effect of prorenin on arterial contractility is yet to be determined. Within rat mesenteric arteries, immunostaining and proximity ligation assays were used to determine the interacting partners of (P)RR in freshly isolated vascular smooth muscle cells (VSMCs). Wire myography examined the functional effect of prorenin. Simultaneous changes in [Ca2+ ]i and force were recorded in arteries loaded with Fura-2AM. Spontaneously transient outward currents were recorded via perforated whole-cell patch-clamp configuration in freshly isolated VSMCs. We found that the (P)RR is located within a distance of less than 40 nm from the V-ATPase, caveolin-1, ryanodine receptors, and large conductance Ca2+ -activated K+ channels (BKCa ) in VSMCs. [Ca2+ ]i imaging and isometric tension recordings indicate that 1 nM prorenin enhanced α1-adrenoreceptor-mediated contraction, associated with an increased number of Ca2+ waves, independent of voltage-gated Ca2+ channels activation. Incubation of VSMCs with 1 nM prorenin decreased the amplitude and frequency of spontaneously transient outward currents and attenuated BKCa -mediated relaxation. Inhibition of the V-ATPase with 100 nM bafilomycin prevented prorenin-mediated inhibition of BKCa -derived relaxation. Renin (1 nM) had no effect on BKCa -mediated relaxation. In conclusion, prorenin enhances arterial contractility by inhibition of BKCa and increasing intracellular Ca2+ release. It is likely that this effect is mediated through a local shift in pH upon activation of the (P)RR and stimulation of the V-ATPase.

Small artery remodeling and stiffening in deoxycorticosterone acetate-salt hypertensive rats involves the interaction between endogenous ouabain/Na + K + -ATPase/cSrc signaling.

OBJECTIVE: Endogenous ouabain (EO) increases in some patients with hypertension and in rats with volume-dependent hypertension. When ouabain binds to Na + K + -ATPase, cSrc is activated, which leads to multieffector signaling activation and high blood pressure (BP). In mesenteric resistance arteries (MRA) from deoxycorticosterone acetate (DOCA)-salt rats, we have demonstrated that the EO antagonist rostafuroxin blocks downstream cSrc activation, enhancing endothelial function and lowering oxidative stress and BP. Here, we examined the possibility that EO is involved in the structural and mechanical alterations that occur in MRA from DOCA-salt rats. METHODS: MRA were taken from control, vehicle-treated DOCA-salt or rostafuroxin (1 mg/kg per day, for 3 weeks)-treated DOCA-salt rats. Pressure myography and histology were used to evaluate the mechanics and structure of the MRA, and western blotting to assess protein expression. RESULTS: DOCA-salt MRA exhibited signs of inward hypertrophic remodeling and increased stiffness, with a higher wall:lumen ratio, which were reduced by rostafuroxin treatment. The enhanced type I collagen, TGFß1, pSmad2/3 Ser465/457 /Smad2/3 ratio, CTGF, p-Src Tyr418 , EGFR, c-Raf, ERK1/2 and p38MAPK protein expression in DOCA-salt MRA were all recovered by rostafuroxin. CONCLUSION: A process combining Na + K + -ATPase/cSrc/EGFR/Raf/ERK1/2/p38MAPK activation and a Na + K + -ATPase/cSrc/TGF-1/Smad2/3/CTGF-dependent mechanism explains how EO contributes to small artery inward hypertrophic remodeling and stiffening in DOCA-salt rats. This result supports the significance of EO as a key mediator for end-organ damage in volume-dependent hypertension and the efficacy of rostafuroxin in avoiding remodeling and stiffening of small arteries.

[Features of the upper gastrointestinal tract mucous membrane state in patients with atherosclerosis of the mesenteric arteries].

AIM: To evaluate the clinical and endoscopic features of diseases of the upper gastrointestinal tract (GIT) in patients with atherosclerosis of the mesenteric arteries (MA). MATERIALS AND METHODS: The study included 48 patients with atherosclerosis of MA and 43 patients without atherosclerosis of MA, who were hospitalized in the department of vascular surgery of the Chelyabinsk Regional Clinical Hospital in the period from 2019 to 2021. All patients underwent multispiral computed tomoangiography of the visceral and lower limb arteries, esophagogastroduodenoscopy. RESULTS: Assessment of lesions of the upper gastrointestinal tract revealed a higher incidence of erosive and ulcerative gastroduodenopathies among patients with atherosclerosis of MA (60.4%), compared with patients without atherosclerosis MA (39.5%); p=0.047. Signs of severe atrophy according to the data of histological examination were statistically significantly more frequent among patients with atherosclerosis of MA (29.2 and 11.6%; p=0.031). According to the results of logistic regression, the following predictors of erosions and ulcers of the upper gastrointestinal tract were revealed: the severity of stenosis of the superior mesenteric artery (SMA) is more than 35%, the body mass index (BMI) is less than 25.9 and the total score on the HADS scale is more than 6.5 points for depression (p=0.008). CONCLUSION: Erosive-ulcerative gastroduodenopathies and atrophy of the gastric mucosa are significantly more common in the group of patients with MA atherosclerosis. The main risk factors for erosions and ulcers of the upper gastrointestinal tract in patients with MA atherosclerosis are: the severity of SMA stenosis is more than 35%, a decrease in BMI is less than 25.9 and an increase in the HADS score is more than 6.5 points.

PFI-3 induces vasorelaxation with potency to reduce extracellular calcium influx in rat mesenteric artery.

Background: PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone. Methods: A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca2+]i, a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells). Results: PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K+-induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K+ channel blockers (Gli/TEA). PFI-3 abolished Ca2+-induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca2+-free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca2+-induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca2+-free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques. Conclusions: PFI-3 blunted PE and high K+-induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs).

ROK and RSK2-kinase pathways differ between senescent human renal and mesenteric arteries.

OBJECTIVE: Small arteries from different organs vary with regard to the mechanisms that regulate vasoconstriction. This study investigated the impact of advanced age on the regulation of vasoconstriction in isolated human small arteries from kidney cortex and periintestinal mesenteric tissue. METHODS: Renal and mesenteric tissues were obtained from patients (mean age 71 ±â€Š9 years) undergoing elective surgery. Furthermore, intrarenal and mesenteric arteries from young and aged mice were studied. Arteries were investigated by small vessel myography and western blot. RESULTS: Human intrarenal arteries (h-RA) showed higher stretch-induced tone and higher reactivity to α 1 adrenergic receptor stimulation than human mesenteric arteries (h-MA). Rho-kinase (ROK) inhibition resulted in a greater decrease in Ca 2+ and depolarization-induced tone in h-RA than in h-MA. Basal and α 1 adrenergic receptor stimulation-induced phosphorylation of the regulatory light chain of myosin (MLC 20 ) was higher in h-RA than in h-MA. This was associated with higher ROK-dependent phosphorylation of the regulatory subunit of myosin light-chain-phosphatase (MLCP), MYPT1-T853. In h-RA phosphorylation of ribosomal S6-kinase II (RSK2-S227) was significantly higher than in h-MA. Stretch-induced tone and RSK2 phosphorylation was also higher in interlobar arteries (m-IAs) from aged mice than in respective vessels from young mice and in murine mesenteric arteries (m-MA) from both age groups. CONCLUSION: Vasoconstriction in human intrarenal arteries shows a greater ROK-dependence than in mesenteric arteries. Activation of RSK2 may contribute to intrarenal artery tone dysregulation associated with aging. Compared with h-RA, h-MA undergo age-related remodeling leading to a reduction of the contractile response to α 1 adrenergic stimulation.

Management of spontaneous isolated mesenteric artery dissection.

Spontaneous isolated mesenteric arterial dissection (SIMAD) is an uncommon subset of non-traumatic dissection of the mesenteric arteries without concurrent aortic dissection. Due to the widespread use of computer tomography angiography, SIMAD cases have been increasingly reported in the past 20 years. Common risk factors associated with SIMAD include male gender, age 50-60 years, hypertension and smoking. This review summarises the diagnostic pathway and management of SIMAD based on contemporary literature and proposes a treatment algorithm for SIMAD. The presentation of SIMAD can be divided into symptomatic and asymptomatic cases. Symptomatic patients should be carefully assessed to detect the development of complications, particularly bowel ischemia or vessel rupture. Although these complications are rare, they necessitate urgent surgical management. The vast majority of symptomatic SIMAD cases are uncomplicated and can be managed safely with conservative treatment that includes antihypertensive therapy, bowel rest, with or without antithrombotic therapy. For asymptomatic SIMAD cases, expectant management with outpatient surveillance imaging appears to be a safe strategy.

Botulinum toxin infusion into the mesenteric artery has selective action on peristalsis in a rat model: experimental research.

OBJECTIVE: Botulinum toxin type A (BoNT/A) reversibly blocks neurotransmission at voluntary and autonomic cholinergic nerve terminals, inducing paralysis. The aim of this study was to block panenteric peristalsis in rats through BoNT/A administration into the superior mesenteric artery (SMA) and to understand whether the toxin's action is selectively restricted to the perfused territory. MATERIALS AND METHODS: Rats were infused through a 0.25-mm surgically inserted SMA catheter with different doses of BoNT/A (10 U, 20 U, 40 U BOTOX®, Allergan Inc.) or with saline for 24 h. Animals were free to move on an unrestricted diet. As a sign of bowel peristalsis impairment, body weight and oral/water intake were collected for 15 days. Statistical analysis was conducted with nonlinear mixed effects models to study the variation over time of the response variables. In three 40 U-treated rats, the selectivity of the intra-arterial delivered toxin action was studied by examining bowel and voluntary muscle samples and checking the presence of BoNT/A-cleaved SNAP-25 (the smoking gun of the toxin action) using the Immunofluorescence (IF) method through a specific antibody recognition. RESULTS: While control rats exhibited an increasing body weight, treated rats showed an initial dose-dependent weight reduction (p<0.001 control vs. treated) with recovery after Day 11 for 10 and 20 U-treated rats. Food and water intake over time showed significantly different half-saturation constants with rats treated with higher doses who reached half of the maximum achievable in a greater number of days (p<0.0001 control vs. treated rats). BoNT/A-cleaved SNAP-25 was identified in bowel wall NMJs and not in voluntary muscles, demonstrating the remarkable selectivity of arterially infused BoNT/A. CONCLUSIONS: Blockade of intestinal peristalsis, can be induced in rats by slow infusion of BoNT/A into the SMA. The effect is long-lasting, dose-dependent and selective. BoNT/A delivery into the SMA through a percutaneous catheter could prove clinically useful in the treatment of entero-atmospheric fistula by temporarily reducing fistula output.

TNF/iNOS/NO pathway mediates host susceptibility to endothelial-dependent circulatory failure and death induced by betacoronavirus infection.

Poor disease outcomes and lethality are directly related to endothelial dysfunction in betacoronavirus infections. Here, we investigated the mechanisms underlying the vascular dysfunction caused by the betacoronaviruses MHV-3 and SARS-CoV-2. Wild-type C57BL/6 (WT) and knockout mice for inducible nitric oxide synthase (iNOS-/-) or TNF receptor 1 (TNFR1-/-) were infected with MHV-3, and K18-hACE2 transgenic mice expressing human ACE2 were infected with SARS-CoV-2. Isometric tension was used to evaluate vascular function. Protein expression was determined by immunofluorescence. Tail-cuff plethysmography and Doppler were used to assess blood pressure and flow, respectively. Nitric oxide (NO) was quantified with the DAF probe. ELISA was used to assess cytokine production. Survival curves were estimated using Kaplan-Meier. MHV-3 infection reduced aortic and vena cava contractility, arterial blood pressure, and blood flow, resulting in death. Resistance mesenteric arteries showed increased contractility. The contractility of the aorta was normalized by removing the endothelium, inhibiting iNOS, genetically deleting iNOS, or scavenging NO. In the aorta, iNOS and phospho-NF-kB p65 subunit expression was enhanced, along with basal NO production. TNF production was increased in plasma and vascular tissue. Genetic deletion of TNFR1 prevented vascular changes triggered by MHV-3, and death. Basal NO production and iNOS expression were also increased by SARS-CoV-2. In conclusion, betacoronavirus induces an endothelium-dependent decrease in contractility in macro-arteries and veins, leading to circulatory failure and death via TNF/iNOS/NO. These data highlight the key role of the vascular endothelium and TNF in the pathogenesis and lethality of coronaviruses.

Phosphodiesterases type 2, 3 and 4 promote vascular tone in mesenteric arteries from rats with heart failure.

Phosphodiesterases (PDE) type 3 and 4 promote vasoconstriction by hydrolysing cAMP. In experimental heart failure (HF), PDE3 makes PDE4 redundant in aorta, but it is not known if this occurs in resistance vessels, such as mesenteric artery. As PDE2 is increased in the failing myocardium, its possible role in the vasculature also needs to be addressed. Here, the function of PDE2, PDE3 and PDE4 in rat mesenteric arteries was characterized in experimental HF. Mesenteric arteries were isolated from rats sacrificed 22 weeks after surgical stenosis of the ascending aorta (HF), or Sham surgery. PDE inhibitors were used to probe isoenzyme contributions in enzymatic and isometric tension assays. PDE2 and PDE4 activities, but not PDE3 activity, facilitate contraction produced by the thromboxane analogue U46619 in Sham arteries, while in HF all three isoenzymes contribute to this response. NO synthase inhibition by L-NAME abolished the action of the PDE2 inhibitor. L-NAME eliminated the contribution of PDE4 in HF, but unmasked a contribution for PDE3 in Sham. PDE3 and PDE4 activities attenuated relaxant response to ß-adrenergic stimulation in Sham and HF. PDE2 did not participate in cAMP or cGMP-mediated relaxant responses. PDE3 and PDE4 cAMP-hydrolysing activities were smaller in HF mesenteric arteries, while PDE2 activity was scarce in both groups. Endothelial cells and arterial myocytes displayed PDE2 immunolabelling. We highlight that, by contrast with previous observations in aorta, PDE4 participates equally as PDE3 in contracting mesenteric artery in HF. PDE2 activity emerges as a promoter of contractile response that is preserved in HF.

Ethanol consumption favors pro-contractile phenotype of perivascular adipose tissue: A role for interleukin-6.

Perivascular adipose tissue (PVAT) exerts anticontractile effect, but under non-physiological conditions it may contribute to vascular dysfunction by releasing pro-inflammatory cytokines. Since PVAT is an important source of interleukin (IL)-6, we evaluated whether this cytokine would contribute to ethanol-induced vascular dysfunction. With this purpose, male C57BL/6 wild-type (WT) or IL-6-deficient mice (IL-6-/-) were treated with ethanol for 12 weeks. Increased blood pressure was evidenced after 4 and 6 weeks of treatment with ethanol in WT and IL-6-/- mice, respectively. In WT mice, ethanol increased plasma and PVAT levels of IL-6. Ethanol favoured pro-contractile phenotype of PVAT in mesenteric arteries from WT, but not IL-6-deficient mice. Functional studies showed that tiron [(a scavenger of superoxide (O2-)] reversed the pro-contractile effect of PVAT in mesenteric arteries from ethanol-treated mice. Ethanol increased the levels of O2- in PVAT from WT mice. Ethanol-induced increase in O2- generation was higher in arteries with PVAT from WT mice when compared to IL-6-deficient mice. Treatment with ethanol augmented myeloperoxidase activity in the mesenteric arterial bed (MAB; with or without PVAT) from WT, but not IL-6-deficient mice. In conclusion, IL-6 contributes to the pro-contractile effect of PVAT by a mechanism that involves increase in ROS generation. Additionally, IL-6 mediates intravascular recruitment of neutrophils in response to ethanol and plays a role in the early stages of ethanol-induced hypertension. Collectively, our findings provide novel evidence for a role of IL-6 in the vascular dysfunction induced by ethanol.

Arterial branching pattern of the cranial mesenteric artery in the degu (Octodon degus).

BACKGROUND: The cranial mesenteric artery exhibits a species-specific ramification pattern that adapts to the morphology of the intestinal tract. The degu is a strictly herbivorous rodent with a well-developed large intestine with a spiral loop in the ascending colon; therefore, the cranial mesenteric artery likely demonstrates a degu-specific ramification pattern. Thus, we traced the cranial mesenteric artery to establish the detailed ramification pattern of the branches. METHODS: Eighteen male degus were injected with 0.3-0.8 ml of a latex mixture and water at a 1:1 ratio in conjunction with red acrylic paint coloring using a catheter inserted into the thoracic aorta. The cranial mesenteric artery was traced using a surgical microscope and photographed using a digital camera. RESULTS: The arteries emerging from the cranial mesenteric artery exhibited frequent variations in number, distribution area, anastomosis pattern, and branching order. In the most frequent cases (22%), the cranial mesenteric artery sequentially gave rise to caudal pancreaticoduodenal, middle colic, right colic, jejunal, and ileocolic arteries. The right and middle colic arteries exhibited four different ramification patterns. In the most common cases (67%), the middle and right colic arteries emerged independently from the cranial mesenteric artery. The former was distributed to the transverse and descending colon, whereas the latter sent branches to the spiral loop of the ascending colon. CONCLUSIONS: The complex ramification pattern of the right colic artery in the degu may be an adaptation to the characteristic running pattern of the ascending colon. Thus, we present the first comprehensive report of the arterial branching pattern of the cranial mesenteric artery in the degu.

Cysteamine Attenuate Intestinal Reperfusion Injury Induced by Occlusion of Mesenteric Artery by Enhancing Intracellular Thiol Activities.

BACKGROUND: Ischemia/reperfusion has been reported to further damage the intestine reperfusion injury (IRI) and cause multiple distal organ dysfunction through oxidative stress, inflammation, and apoptosis. Cysteamine is known to inhibit oxidative stress, inflammatory cytokines and apoptosis. This experiment was designed to evaluate the role of cysteamine against IRI in rats METHODS: Thirty-two Wistar rat strains were assigned to four groups: sham, Intestinal-reperfusion injury (IRI), 50 mg/kg and 100 mg/kg cysteamine treatment IRI. A 5 cm segment of terminal ileum was twisted 360° clockwise along the mesentery for 45 minutes to induce ischemia before detorsion. Tissues were preserved for biochemical evaluation and histology 4 hours after detorsion. Activities of GPx, GSH, protein and non-protein thiol, H2O2, MDA were evaluated. Serum concentration of nitrite, MPO, ALT, AST TNF-alpha and IL-6 were measured. Caspase 3 and bax were evaluated by immunohistochemistry. Statistical significance was set as p<0.05 RESULTS: Significant (p<0.05) increase in H2O2, MDA and nitrite but reduction in GPx, GSH, protein thiol and non-protein thiol in the IRI rats was reversed by 50 and 100 mg/kg cysteamine. Serum MPO, TNF-α, IL6, AST and ALT was significantly elevated in IRI while the rats treated with cysteamine showed a significant decrease (p<0.05) in the activities of these inflammatory and hepatic injury markers. CONCLUSION: Cysteamine mitigate IRI by enhancing intracellular antioxidant defense system, inhibiting inflammatory mediators and intestinal tissue expression of pro-apoptotic protein.