Carbon monoxide-triggered health effects: the important role of the inflammasome and its possible crosstalk with autophagy and exosomes.

Carbon monoxide (CO) has long been known as a "silent killer" because of its ability to bind hemoglobin (Hb), leading to reduced oxygen carrying capacity of Hb, which is the main cause of CO poisoning (COP) in humans. Emerging studies suggest that mitochondria is a key target of CO action that can impact key biological processes, including apoptosis, cellular proliferation, inflammation, and autophagy. Despite its toxicity at high concentrations, CO also exhibits cyto- and tissue-protective effects at low concentrations in animal models of organ injury and disease. Specifically, CO modulates the production of pro- or anti-inflammatory cytokines and mediators by regulating the NLRP3 inflammasome. Given that human diseases are strongly associated with inflammation, a deep understanding of the exact mechanism is helpful for treatment. Autophagic factors and inflammasomes interact in various situations, including inflammatory disease, and exosomes might function as the bridge between the inflammasome and autophagy activation. Thus, the interplay among autophagy, mitochondrial dysfunction, exosomes, and the inflammasome may play pivotal roles in the health effects of CO. In this review, we summarize the latest research on the beneficial and toxic effects of CO and their underlying mechanisms, focusing on the important role of the inflammasome and its possible crosstalk with autophagy and exosomes. This knowledge may lead to the development of new therapies for inflammation-related diseases and is essential for the development of new therapeutic strategies and biomarkers of COP.

Risks of Developing Diabetes and Hyperglycemic Crisis Following Carbon Monoxide Poisoning: A Study Incorporating Epidemiologic Analysis and Animal Experiment.

Purpose: Carbon monoxide (CO) poisoning may damage the pancreas, but the effects of CO poisoning on the development of diabetes and on existing diabetes remain unclear. We conducted a study incorporating data from epidemiologic analyses and animal experiments to clarify these issues. Methods: Using the National Health Insurance Database of Taiwan, we identified CO poisoning patients diagnosed between 2002 and 2016 (CO poisoning cohort) together with references without CO poisoning who were matched by age, sex, and index date at a 1:3 ratio. We followed participants until 2017 and compared the risks of diabetes and hyperglycemic crisis between two cohorts using Cox proportional hazards regressions. In addition, a rat model was used to assess glucose and insulin levels in blood as well as pathological changes in the pancreas and hypothalamus following CO poisoning. Results: Among participants without diabetes history, 29,141 in the CO poisoning cohort had a higher risk for developing diabetes than the 87,423 in the comparison cohort after adjusting for potential confounders (adjusted hazard ratio [AHR]=1.23; 95% confidence interval [CI]: 1.18-1.28). Among participants with diabetes history, 2302 in the CO poisoning cohort had a higher risk for developing hyperglycemic crisis than the 6906 in participants without CO poisoning (AHR = 2.12; 95% CI: 1.52-2.96). In the rat model, CO poisoning led to increased glucose and decreased insulin in blood and damages to pancreas and hypothalamus. Conclusion: Our epidemiological study revealed that CO poisoning increased the risks of diabetes and hyperglycemic crisis, which might be attributable to damages in the pancreas and hypothalamus as shown in the animal experiments.

Increased Risk of Congestive Heart Failure Following Carbon Monoxide Poisoning.

BACKGROUND: Carbon monoxide poisoning (COP) is an important public health issue around the world. It may increase the risk of myocardial injury, but the association between COP and congestive heart failure (CHF) remains unclear. We conducted a study incorporating data from epidemiological and animal studies to clarify this issue. METHODS: Using the National Health Insurance Database of Taiwan, we identified patients with COP diagnosed between 1999 and 2012 and compared them with patients without COP (non-COP cohort) matched by age and the index date at a 1:3 ratio. The comparison for the risk of CHF between the COP and non-COP cohorts was made using Cox proportional hazards regression. We also established a rat model to evaluate cardiac function using echocardiography and studied the pathological changes following COP. RESULTS: The 20 942 patients in the COP cohort had a higher risk for CHF than the 62 826 members in the non-COP cohort after adjusting for sex and underlying comorbidities (adjusted hazard ratio, 2.01 [95% CI, 1.74-2.32]). The increased risk of CHF persisted even after 2 years of follow-up (adjusted hazard ratio, 1.85 [95% CI, 1.55-2.21]). In the animal model, COP led to a decreased left ventricular ejection fraction on echocardiography and damage to cardiac cells with remarkable fibrotic changes. CONCLUSIONS: Our epidemiological data showed an increased risk of CHF was associated with COP, which was supported by the animal study. We suggest close follow-up of cardiac function for patients with COP to facilitate early intervention and further studies to identify other long-term effects that have not been reported in the literature.

Oxytocin maintains lung histological and functional integrity to confer protection in heat stroke.

Oxytocin (OT) has been reported to have a protective effect in lipopolysaccharide-induced experimental acute lung injury (ALI). However, its role in heat stroke-related ALI has never been investigated. Herein, we aimed to explore the therapeutic effects and potential mechanism of action of OT on heat-induced ALI. Rats were treated with OT 60 min before the start of heat stress (42 °C for 80 min). Twenty minutes after the termination of heat stress, the effects of OT on lung histopathological changes, edema, acute pleurisy and the bronchoalveolar fluid levels of inflammatory cytokines and indicators of ischemia, cellular damage, and oxidative damage were assessed. We also evaluated the influence of OT pretreatment on heat-induced hypotension, hyperthermia, ALI score, and death in a rat model of heat stroke. The results showed that OT significantly reduced heat-induced lung edema, neutrophil infiltration, hemorrhage score, myeloperoxidase activity, ischemia, and the levels of inflammatory and oxidative damage markers in bronchoalveolar lavage fluid. The survival assessment confirmed the pathophysiological and biochemical results. An OT receptor antagonist (L-368,899) was administered 10 min before the OT injection to further demonstrate the role of OT in heat-induced ALI. The results showed that OT could not protect against the aforementioned heat stroke responses in rats treated with L-368,899. Interestingly, OT treatment 80 min after the start of heat shock did not affect survival. In conclusion, our data indicate that OT pretreatment can reduce the ischemic, inflammatory and oxidative responses related to heat-induced ALI in rats.