Effect of allantoin on experimentally induced gastric ulcers: Pathways of gastroprotection

Abstract

Gastric ulcer affects people worldwide, and its inefficacy and recurrence have fueled the search for new therapeutic strategies. Despite the well-known use of allantoin in medicines and cosmetic products, its effect has not yet been studied with regard to gastric ulcer. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of allantoin against commonly harmful agents that cause injuries to the stomach. Ethanol, indomethacin, and stress-induced gastric ulcer models were adopted, in addition to pylorus ligature, a quantification of vascular permeability, glutathione (GSH), gastric adhered mucus, prostaglandin (PGE), pro-inflammatory cytokines levels, myeloperoxidase (MPO), and catalase (CAT) activities. The gastric lesions were examined by gross, histological, and ultrastructural features. The results showed that treatment with allantoin (60mg/kg, per oral) reduced the gastric ulcer formation in all models. Furthermore, allantoin reduced the parameters of gastric acid secretion and attenuated both the vascular permeability and MPO activity. The levels of pro-inflammatory cytokines were also reduced, accompanied by a restoration of CAT activity and GSH levels. Notably, allantoin treatment preserved the gastric-adhered mucus and PGE levels after ethanol administration. Microscopic and ultrastructural analysis revealed that allantoin maintained tissue integrity and prevented morphological changes in cells caused by ethanol. In summary, we demonstrated for the first time that allantoin possesses gastroprotective activity through anti-inflammatory, anti-oxidative, antisecretory, and cytoprotective mechanisms. The antisecretory and cytoprotective mechanisms are probably associated with an increase in PGE levels.

Allantoin improves histopathological evaluations in a rat model of gastritis

“…In this context, it has been reported that allantoin decreased IL4, IL5, and inflammatory cell infiltration in asthma-induced rats (11). Furthermore, da Silva et al (7) have recently shown that allantoin decreases TNFα and IL1β in gastritis induced in female mice. Our results are in agreement with these documents and demonstrate anti-inflammatory effects of allantoin in the ethanolinduced gastritis in male rats.…”

“…In another experiment, allantoin improved cognitive function and neurogenesis in the mice hippocampus (1). Interestingly, da Silva et al (7) have recently reported the gastroprotective effect of allantoin on gastric ulcer in female mice. Based on these observations, we designed experiments to study the treatment effect of allantoin on ethanol-induced gastritis in male rats.…”

Deciphering the Mechanical Network of Chronic Atrophic Gastritis: A Urinary Time-Dependent Metabonomics-Based Network Pharmacology Study

“…Allantoin, a product of purine metabolism, was an indication of high levels of reactive oxygen species via non-enzymatic means. da Silva et al (2018) also reported that allantoin could possess gastroprotective activity through anti-inflammatory, anti-oxidative, antisecretory and cytoprotective mechanisms. It was also found to be depressed under CAG condition, indicated that the pathology of inflammatory, oxidative, and secretory participated into the development of CAG.…”

Natural Film Based on Pectin and Allantoin for Wound Healing: Obtaining, Characterization, and Rat Model

“…The use of this polysaccharide has been explored as a functional source for biomedical and pharmaceutical applications, such as the development of scaffolds for the release of drugs, wound healing, and tissue engineering, due to its natural gelling mechanism and high availability besides its nontoxic nature [ 7 – 11 ]. On the other hand, allantoin is a white powder highly used as a natural ingredient not only in cosmetic products but also in pharmaceutical products for skin diseases [ 6 – 8 ], since one of the main effects of this compound is the strong stimulation of cell proliferation and the reconstruction of intact granulation tissue, which justifies its use as an active ingredient unique in pharmaceutical preparations, which has been proven effective to treat ulcers, healing wounds, and burns[ 12 – 14 ].…”