Folic Acid Supplementation Ameliorates Inflammation and Apoptosis in Ethanol-Induced Gastric Ulceration in Rats

Abstract

Although the gastroprotective potential of folic acid has been reported, little is known about the role of inflammation and apoptosis in the said activity. This study, therefore, assessed lipid peroxidation (LPO), Neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP) as markers of inflammation and, p53 and BCl-2 as markers of apoptosis in ethanol-induced gastric ulcer pretreated with Folic acid (FA) for twenty-one (21) days. Adult male Wistar rats were arranged into experimental groups (n = 5) viz: 1) Control; 2) Ulcer control; 3) 2FA (2 mg/kg folic acid + Ulcer); 4) 3FA (3 mg/kg folic acid + Ulcer); 5) OMEP (20 mg/kg omeprazole + Ulcer); 6) 2FA + OMEP + Ulcer; and 7) 3FA + OMEP + Ulcer. Ulcer score, LPO, NLR, serum CRP were all determined one hour post ulcer induction. Paraffin gastric sections were stained first with H & E, then immunostained for p53 and BCl-2. Ethanol caused gastric lesion with an index of 3.0 ± 0.2. Ulcer severity and LPO was significantly decreased in the 2FA, 3FA, OMEP, 2FA + OMEP and 3FA + OMEP groups. NLR reduced significantly in the 2FA, 3FA, OMEP and OMEP + 3FA group. Qualitatively, there was absence of C-reactive protein in the 2FA group while quantitatively, presence of CRP appeared sustained in the 3FA and OMEP treated groups. Unlike p53, the expression and labeling index of BCl-2 were significantly enhanced more in the FA and OMEP combination than OMEP alone. Folic acid ameliorates the development of gastric ulcer in rats via its anti-inflammatory and anti-apoptotic activities.

Causal Association of Folic Acid Supplementary Therapy and Gastric Ulcer: A Mendelian Randomization Study

“…A recent study demonstrated that folate supplementation enhanced the expression of angiogenesis-related factors such as EGF and VEGF, increased the expression of Ki-67 related to cell proliferation, and reduced the severity of ulcers in mice with GU [21]. In addition, folate can protect gastric mucosa from ethanolinduced acute damage through anti-in ammatory and anti-apoptotic mechanisms [20]. However, it should be noted that high-dose folate may damage the integrity of gastric mucosa, as suggested by some studies [19].…”

“…However, the potential impact of folic acid on gastric mucosa has received little attention. Several studies have demonstrated that pretreatment with folic acid can effectively prevent the formation of gastric ulcers [17][18][19][20][21]. Nevertheless, most of these studies have been limited to the animal and cellular level and lack of clinical and genetic evidence, which limits their reliability.…”