Abstract
Aspirin has been widely recommended for acute and chronic conditions for over 2,000 years. Either single or repetitive doses are commonly used for analgesic and antipyretic reasons and to prevent heart attacks, stroke, and blood clot formation. Recent studies show that it can also be used chronically to dramatically reduce the risk of a variety of cancers. However, prolonged usage of aspirin can cause severe damage to the mucosal barrier, increasing the risk of ulcer formation and GI-bleeding events. In the present study, we show the effects of acute low-dose aspirin exposure as an active secretagogue-inducing gastric acid secretion. Studies were carried out with isolated gastric glands using the pH-sensitive dye BCECF-AM to assess acid secretion. The non-selective NOS inhibitor L-NAME (30 μM), or the specific inhibitor ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one) was applied while monitoring intracellular pH. The effects of basolateral exposure to aspirin (acetylsalicylic acid, ASA) caused activation of gastric acid secretion via the H+, K+-ATPase. Our data suggest that aspirin increases nitric oxide (NO) production, which in turn activates acid secretion. Exposure of gastric glands to either the non-selective NOS inhibitor L-NAME, and the highly selective, soluble guanylyl cyclase inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) effectively inhibited aspirin-dependent gastric acid secretion. Aspirin can be considered as a novel secretagogue, in the way that it activates the H+, K+-ATPase. With increased daily aspirin consumption, our findings have important implications for all individuals consuming aspirin even in low doses and the potential risks for increased acid secretion.
Highlights
Salicylate use as a medicinal agent dates back to antiquity, and to this date, aspirin remains one of the most frequently used pharmaceuticals worldwide (Baron et al, 2013)
The aspirin pHi recovery rate showed a highly significant difference in ΔpH/min compared to non-stimulated conditions, (p < 0.0001) (Figure 2A)
Our results demonstrate a significant decrease of gastric acid secretion in the presence of L-NAME compared to aspirin-induced gastric acid secretion [0.0372 ± 0.00629 ΔpH/min (n = 40) vs. 0.0004409 ± 0.001308 ΔpH/min (n = 85), p < 0.0001] (Figure 3A)
Summary
Salicylate use as a medicinal agent dates back to antiquity, and to this date, aspirin (acetylsalicylic acid, ASA) remains one of the most frequently used pharmaceuticals worldwide (Baron et al, 2013). Studies show that similar low-dose aspirin consumption for extended periods can reduce risk of melanoma (Joosse et al, 2009; Zhu et al, 2015), and pancreatic cancer (Risch et al, 2017). These protective effects have been suggested to be via the inhibition of the COX enzymes, which further reduces inflammatory and immune responses, and is one of the main mechanisms involved in decreasing tumor risk of colonic malignancies (Lanas et al, 2011). The effect of aspirin varies by dose: at low dosage (
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