Effects of Lupeol on Intestinal Anastomosis After Experimental Intestinal Ischemia-Reperfusion Injury in Rats.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S501289

Cem Kaya, Alparslan Kapisiz, Sibel Eryilmaz, Ramazan Karabulut, Zafer Turkyilmaz, Mehmet Arda Inan, Gizem Yaz Aydin, Mert Alperen Celik, Kaan Sonmez

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引用次数: 0

Abstract

Background: Intestinal ischemia/reperfusion (I/R) injury can occur in a wide variety of diseases and surgeries. If necessary, the blood flow should be restored, including re-anastomosis by removing the intestines with impaired circulation. In this process, anastomotic strength is as important as inflammatory responses and oxidative stress. Therefore, we conducted the study to investigate the effects of lupeol on intestinal ischemia-reperfusion injury, not only biochemically and histopathologically but also on anastomotic strength and miRNAs.

Methods: Female rats were randomly divided into six groups. While only laparotomy was performed in the control group (Group C), anastomosis was performed in the sham group (Group S). In the other groups, the superior mesenteric artery was clamped for 45 minutes. In the groups I/R¹ and L¹, the intestine was transected, and end-to-end anastomosis was performed at the 1st hour of reperfusion. In the groups I/R²⁴ and L²⁴, this procedure was performed at the 24th hour of reperfusion. In addition, lupeol treatment was given before reperfusion and for the following 4 days in the groups L¹ and L²⁴. All rats, except the control group, bursting pressure was measured on the 5th day of anastomosis, and then all rats including the control group were sacrificed. TNF-α, IL-6 levels in blood samples and MDA, GSH, caspase-3, miR-29b-3p, miR-34a-5p, miR-495-3p levels in intestinal tissues were measured, and intestinal histopathology was also examined.

Results: Lupeol treatment, which was statistically significant in some parameters, demonstrated positive effects by decreasing TNF, IL-6, MDA, caspase-3, histopathological damage levels and increasing GSH and bursting pressure. In addition, lupeol decreased miR-34a-5p expression and increased miR-29b-3p and miR-495-3p expression.

Conclusion: Lupeol protected the intestines from I/R damage with its antioxidant and anti-inflammatory effects. Besides, it reduced the histopathological damage and increased the anastomotic strength. Additionally, miR-29b-3p, miR-34a-5p, miR-495-3p expressions were altered by lupeol.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.