Citral Modulates MMP-2 and MMP-9 Activities on Healing of Gastric Ulcers Associated with High-Fat Diet-Induced Obesity

• Published in: International journal of molecular sciences 2023-03, Vol.24 (5), p.4888
• Main Authors: Ohara, Rie, Dario, Felipe Lima, Emílio-Silva, Maycon Tavares, Assunção, Renata, Rodrigues, Vinícius Peixoto, Bueno, Gabriela, Raimundo, Priscila Romano, da Rocha, Lúcia Regina Machado, Hiruma-Lima, Clelia Akiko
• Format: Article
• Language: English
• Subjects: Abdomen; Acetic acid; Animals; Body fat; Cell adhesion & migration; Citral; Comorbidity; Cytokines; Diet; Diet, High-Fat; Disease; Enzymes; Fibroblasts; Gastric mucosa; Gastric Mucosa - pathology; Gelatinase A; Gelatinase B; Healing; High fat diet; Inflammation; Lesions; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9 - pharmacology; Matrix metalloproteinases; Mice; Natural products; Nonsteroidal anti-inflammatory drugs; Obesity; Obesity - pathology; Oral administration; Organic acids; Physiology; Stomach Ulcer - pathology; Tumor necrosis factor-TNF; Ulcer - pathology; Ulcers
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054888

Obesity causes low-grade inflammation that results in the development of comorbidities. In people with obesity, exacerbation of gastric lesion severity and delayed healing may aggravate gastric mucosal lesions. Accordingly, we aimed to evaluate the citral effects on gastric lesion healing in eutrophic and obese animals. C57Bl/6 male mice were divided into two groups: animals fed a standard diet (SD) or high-fat diet (HFD) for 12 weeks. Gastric ulcers were induced using acetic acid (80%) in both groups. Citral (25, 100, or 300 mg/kg) was administered orally for 3 or 10 days. A vehicle-treated negative control (1% Tween 80, 10 mL/kg) and lansoprazole-treated (30 mg/kg) were also established. Lesions were macroscopically examined by quantifying regenerated tissue and ulcer areas. Matrix metalloproteinases (MMP-2 and -9) were analyzed by zymography. The ulcer base area between the two examined periods was significantly reduced in HFD 100 and 300 mg/kg citral-treated animals. In the 100 mg/kg citral-treated group, healing progression was accompanied by reduced MMP-9 activity. Accordingly, HFD could alter MMP-9 activity, delaying the initial healing phase. Although macroscopic changes were undetectable, 10-day treatment with 100 mg/kg citral exhibited improved scar tissue progression in obese animals, with reduced MMP-9 activity and modulation of MMP-2 activation.