Cannabidiol reduces lung injury induced by hypoxic–ischemic brain damage in newborn piglets

Abstract

BackgroundBrain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.MethodsNewborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT receptor antagonist) after HI brain damage (carotid flow interruption and FiO 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1β concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).ResultsCBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.ConclusionsCBD reduced brain HI-induced distant lung damage, with 5-HT receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.

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“…Moreover, CBD was able to directly suppress T-cell secretion of IL-1 and IFNγ [45]. In piglets with hypoxic-ischemic lung damage, CBD reduced histologic damage, decreased leukocyte infiltration and modulated IL-1 concentration in bronchoalveolar lavage fluid [46], while in a rat model of sepsis, CBD reversed oxidative stress and reduced mortality [47]. In humans, cannabinoid use prevented induction of pro-inflammatory CD16 + monocytes and production of IP-10, suggesting anti-inflammatory effects in humans [48].…”

The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease

“…Cannabidiol is considered as promising neuroprotectant after neonatal hypoxia-ischemia and as mentioned above, in European Union, this compound has even orphan drug status in perinatal asphyxia. The largest number of evidence of protective CBD action in HIE is based on studies in newborn piglets submitted to hypoxia-ischemia [54,[127][128][129][130][131] (Table 4). Beneficial effects of CBD on experimental neonatal HIE include alleviation of decreased brain activity [54,[127][128][129][130][131], neuronal metabolism impairment [127][128][129]131], excitotoxicity [54,129], histopathological changes in brain [127,128], neuronal necrosis and/or apoptosis [54,[129][130][131], astroglial and/or microglial activation [131], neuroinflammation [54,[128][129][130][131] and oxidative stress in brain [54,130,131].…”

“…Beneficial effects of CBD on experimental neonatal HIE include alleviation of decreased brain activity [54,[127][128][129][130][131], neuronal metabolism impairment [127][128][129]131], excitotoxicity [54,129], histopathological changes in brain [127,128], neuronal necrosis and/or apoptosis [54,[129][130][131], astroglial and/or microglial activation [131], neuroinflammation [54,[128][129][130][131] and oxidative stress in brain [54,130,131]. CBD can also diminish distant inflammatory lung damage associated with brain hypoxia-ischemia-induced injury [130]. In addition, CBD might diminish hypoxia-ischemia-induced decrease in blood pressure [54,127,[129][130][131].…”

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

“…interleukin (IL)-4, IL-10) [190,191,23] and inhibit production of pro-inflammatory cytokines (e.g. IL-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α) [10,50,55,62,63,113,130,149,154,186] and reactive oxygen species [62,130,186]. Models demonstrating such effects have included lung injury induced by chemical treatment [149] and hypoxic-ischemia (HI) [10]; liver injury induced by ischemia-reperfusion [63,130] and alcohol feeding [186]; myocardial [55] and renal [62] ischemia-reperfusion injuries; surgically induced oral lesions [102]; chemically induced osteoarthritis [145]; spinal cord contusion injury [113], and colitis [23,50,154] (see Burstein [24] for review).…”