Protective Effect and Mechanism of Alprostadil in Acute Respiratory Distress Syndrome Induced by Oleic Acid in Rats

Abstract

BackgroundThis study investigated the role and mechanism of alprostadil in acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats.Material/MethodsSprague-Dawley rats were randomly divided into control, OA model, and OA + Alprostadil (2.5, 5, and 10 μg/kg, respectively) groups. The ARDS model was induced by femoral vein injection of OA, and alprostadil was administrated immediately. Lung injury was evaluated by lung wet-dry weight ratio (W/D) and histological analyses. Expressions of ACE, inflammatory mediators, apoptotic-related proteins, and proteins in the MAPKs and NF-κB signaling pathways were determined by Western blot or immunohistochemical staining.ResultsCompared with the control group, the OA model group had significantly increased W/D, lung injury score, and collagen deposition at 3 h after OA injection. However, alprostadil (10 μg/kg) treatment significantly reduced OA-induced elevation of these indicators. Additionally, OA-induced expression of TNF-α and IL-1β were suppressed by alprostadil. The OA-induced activation of nuclear factor (NF) κB p65 was also reduced by alprostadil. Furthermore, we found that Alprostadil had an inhibitory effect on the phosphorylation of JNK, ERK1/2, and p38 MAPKs. Alprostadil inhibited Bax but increased Bcl-2, indicating a suppressive role in apoptosis. Remarkably increased expression of ACE in the OA model group was observed, which was decreased by alprostadil.ConclusionsAlprostadil has a protective effect on ARDS induced by OA in rats, possibly through inhibiting apoptosis, suppressing the activation of MAPKs and NF-κB signaling pathways, and decreasing ACE protein expression. Therefore, the use of alprostadil in clinical ARDS treatment is promising.

Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid‐induced acute lung injury

“…OA causes ALI/ARDS in rats by inducing the cytokine cascade by upregulating the expression of various proinflammatory cytokines, such as TNF‐α and IL‐1β. Similar to earlier studies, OA in our study synergistically elevated the expression of TNF‐α and IL‐1β in lung tissue 20,62,63 . These cytokines stimulate the production of additional proinflammatory cytokines and chemokines by encouraging the expression of IL‐6 and IL‐8 in other cells.…”

“…Similar to earlier studies, OA in our study synergistically elevated the expression of TNF-α and IL-1β in lung tissue. 20,62,63 These cytokines stimulate the production of additional which supports these PCR results. In our research, it was also discovered that the OA group had higher levels of IL-8 expression.…”

“…Three hours after OA administration, all animals were euthanized, and the lungs were excised. The OA treatment protocol, OA dose, and OA‐induced ALI model procedures were described previously, respectively 20,21 . The lung tissues were collected and used for histological, biochemical, and molecular research.…”

Alprostadil associated with low molecular weight heparin to treat limb ischemia caused by SARS-CoV2

“…It is the naturally occurring prostaglandin E1 (PGE1), a potent vasodilator agent with several pharmacologic actions, including increased peripheral blood flow and inhibition of platelet aggregation. 14 In rats, Alprostadil had a positive effect on acute respiratory distress syndrome (ARDS), possibly through suppressing the nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) signaling pathway and decreasing ACE expression, 15 both important mechanisms in COVID-19.…”

“…In rats, Alprostadil had a positive effect on acute respiratory distress syndrome (ARDS), possibly through suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway and decreasing ACE expression, 15 both important mechanisms in COVID-19.…”