Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway

Abstract

Previous studies have shown that carbon monoxide (CO) is involved in a variety of physiological and pathophysiological processes including anti-inflammatory, anti-apoptotic and anti-oxidant responses. However, it remains unclear whether CO promotes gastric ulcer healing. In the present study, we evaluated the efficacy of CO-saturated saline in the treatment of gastric ulcers and its underlying mechanism. Acute gastric ulcers were induced in C57BL/6 male mice using acetic acid. A CO-saturated solution was prepared by bubbling 50% CO gas into saline. To investigate the effect of CO on gastric mucosal healing, CO solution was orally administrated twice a day beginning on day 3 after the induction of gastric ulcer. Mice were sacrificed on day 7 after ulcer induction. The stomach was removed, and the ulcerated lesions were measured. In vitro wound healing assays were used to determine the mechanism of action of CO in the restoration of murine gastric epithelial cells. The oral administration of CO solution accelerated the gastric ulcer healing by promoting re-epithelialization. Furthermore, the wound healing assay performed using the murine gastric epithelial cells revealed that the CO-saturated medium enhanced cell migration through the activation of protein kinase C (PKC). Based on these data, CO may represent a novel therapeutic approach for the treatment of gastric mucosal injuries.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…Similar anti‐inflammatory activities of CO have also been established in mice models of experimental autoimmune encephalomyelitis and experimental cerebral malaria, which might imply that CO has the potential to prevent neuroinflammation in humans . Moreover, CO has been recognized as a potential new treatment for inflammatory disorders of the digestive system such as postoperative ileus, inflammatory bowel disease, gastric ulcers, diabetic gastroparesis, and acute liver injury . Another important field of anti‐inflammatory therapy using CO is sepsis.…”

Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre‐existing gastric ulcers

“…Interestingly, CO produced endogenously or released from its pharmacological donors, including tricarbonyldichlororuthenium (II) dimer (CORM-2), has been demonstrated to protect the gastric mucosa against the damage induced by exposure to systemic stress or the administration of ethanol, alendronate or aspirin (ASA) (Gomes et al, 2010;Magierowska et al, 2015Magierowska et al, , 2016Magierowski et al, 2016a,b;Kwiecien et al, 2016). Interestingly, COsaturated saline promotes gastric ulcer healing, but the mechanism of this beneficial effect on ulcer healing has been little studied (Takagi et al, 2016). In particular, the involvement of CO-releasing CORM-2 in the healing of preexisting gastric ulcers has not been investigated so far.…”

The role of hydrogen sulfide in gastric mucosal damage

“…New evidence suggests that HMOX-1 is not directly involved in anti-oxidative stress and other reactions, but by up-regulating CO to protect 50. In terms of its role in gastric mucosa, CO exhibits its anti-inflammatory, anti-apoptotic and anti-oxidant responses in many ways 51. A large number of studies have found that the three of them interact with each other 5253.…”