Methanolic Moringa oleifera leaf extract protects against epithelial barrier damage and enteric bacterial translocation in intestinal I/R: Possible role of caspase 3

Abstract

Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI.Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS.Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3.Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid.

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

“…The abdomen was shaved and washed with normal saline solution and a sterile eye-field was placed over the operative site. As described by Afolabi et al, [17] midline incision on the abdomen the cecum and terminal ileum were mobilized and the ileocaecal junction identified. A 5 cm segment of the terminal ileum 5 cm from the ileo-cecal junction (ICJ) was twisted 360 0 clockwise along the mesentery (to cause ischemia) and anchored to the anterior abdominal wall with 2-0 chromic suture.…”

“…# Values differ significantly from reperfusion injury (#p < 0.05, ##p < 0.01, ### p < 0.001).▶Fig. 2 Bar chart showing the effect of reperfusion injury and cysteamine on the intestinal tissue level of GSH and GPx using ellman reagents as described by Oladele[17]. Values were expressed as mean ± SEM, for eight rat per group.…”

When less is more: Experimental Bishop–Koop technique for reduction in the use of laboratory animals for intestinal pathophysiological studies

“…For example, in the SI, superior mesenteric artery clamping model is currently used to evaluate IIRI, requiring one animal for each sample and study time. 15–29 The same situation occurs in the field of experimental colitis, where old and recent scientific articles use one animal in each LI sample collection. 30–37 For the reasons mentioned above, it is a challenge to develop models that enable reducing the number of animals involved in these studies.…”

“…Among experimental studies focused on gastrointestinal diseases found in the literature, IIRI- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats appears as a current model used by many authors and research groups around the world. 20–37 For this reason, we selected these two relevant pathologies to evaluate the experimental BK procedure in an intestinal injury scenario. IIRI was used for simulating a model of intestinal intussusception, strangulated hernia or intestinal transplantation.…”

Efectos del precondicionamiento isquémico abdominal multiorgánico en modelos experimentales de isquemia-reperfusión

“…De los estudios experimentales focalizados en patología de intestino delgado la IIR es un modelo de interés en la actualidad. (91)(92)(93)(94)(95)(96)(97)(98)(99)(100) Materiales y métodos: Se emplearon ratas Wistar hembras (peso 221 ± 13 gr). A las mismas se les proporcionó agua y alimento a demanda previo al acto quirúrgico.…”