The dose of menthol used in this study was selected based on previous results reported by our group showing the gastroprotective effect of menthol. It was observed that treatment with menthol provided 92% gastroprotection compared to treatment with a vehicle control; this level of gastroprotection that is similar to the effect of the standard drug carbenoxolone. The mechanisms responsible for the gastroprotective effect were also investigated. HSPs are a type of protective protein involved in diverse biological activities, including apoptosis. Gomisin-D HSP-70 is a molecular chaperone that is rapidly induced by stresses such as heat, oxidative stress, and drug exposure. Therefore, drugs or treatments that induce HSP-70 expression may positively contribute to gastric mucosal defense and cytoprotection. In addition to its cytoprotective effect, HSP-70 has anti-apoptotic activity and can decrease oxidative stress and cell injury. The induction of HSP-70 is part of the gastroprotective mechanism of menthol. Furthermore, the inhibition of apoptosis in the gastric mucosa of rats treated with menthol can be partially explained by menthol’s HSP-70-inducing effect. It has been suggested that an interaction between the expression of the HSP-70 and the proapoptotic Bax genes may occur under stress conditions, with suppression of Bax activation in cells with high HSP-70 levels. There is growing evidence that ethanol administration promotes oxidative stress by increasing the Tetrahydroberberine formation of ROS and depleting cellular oxidative defenses in a process triggered by neutrophil activation, causing a sequential ROS-mediated induction of lipid peroxidation and protein oxidation. Recent studies have linked the genesis of ethanol-induced gastric ulcers to the number of infiltrated neutrophils. The MPO is the main marker of neutrophil infiltration in ulcerogenic lesions. This enzyme is found within the neutrophils and catalyzes the oxidation of the chloride ion by hydrogen peroxide to form hypochlorous acid, which is toxic to pathogenic microorganisms but is also harmful to host tissues. This process is responsible for the generation of free radicals, resulting in an acute inflammation in the gastric tissue. The gastroprotection induced by menthol can be partially explained by the inhibition of neutrophil infiltration and subsequent MPO generation. Neutrophils also produce the superoxide radical anion, the product of the reaction of oxygen molecules and electrons from the transport chain in mitochondria. The cells of the gastrointestinal tract have an antioxidant defense system 
that is capable of preventing the cytotoxicity of ROS through mechanisms that involve the action of enzymes and compounds with the potential to scavenge free radicals and prevent their destructive action. The major antioxidative enzyme is SOD, which catalyzes the dismutation of O22 into less noxious H2O2, which is further degraded by catalase or GSH-Px. The activity of SOD was decreased in the stomachs of mentholor carbenoxolone-treated rats. We propose that this is an interesting finding because the relatively higher SOD activity in vehicle-treated rats indicates a greater production of O22. The increases in the amounts of the GSH-Px and GR enzymes and the antioxidant compound glutathione, associated with the inhibition of MPO production, confirm the antioxidant activity of the menthol in gastric ulcers and support an important role for oxidative stress in the pathogenesis of ethanol-induced gastric ulcers. There are several reports in the literature indicating that the administration of potential antioxidant natural products can prevent the gastric damage caused by the action of ethanol.