Pretreatment with Coenzyme Q10 Combined with Aescin Protects against Sepsis-Induced Acute Lung Injury

Abstract

Sepsis-associated acute lung injury (ALI) is a critical condition characterized by severe inflammatory response and mitochondrial dysfunction. Coenzyme Q10 (CoQ10) and aescin (AES) are well-known for their anti-inflammatory activities. However, their effects on lipopolysaccharide (LPS)-induced lung injury have not been explored yet. Here, we asked whether combined pretreatment with CoQ10 and AES synergistically prevents LPS-induced lung injury. Fifty male rats were randomized into 5 groups: (1) control; (2) LPS-treated, rats received a single i.p. injection of LPS (8 mg/kg); (3) CoQ10-pretreated, (4) AES-pretreated, or (5) combined-pretreated; animals received CoQ10 (100 mg/kg), AES (5 mg/kg), or both orally for 7 days before LPS injection. Combined CoQ10 and AES pretreatment significantly reduced lung injury markers; 52.42% reduction in serum C-reactive protein (CRP), 53.69% in alkaline phosphatase (ALKP) and 60.26% in lactate dehydrogenase (LDH) activities versus 44.58, 37.38, and 48.6% in CoQ10 and 33.81, 34.43, and 39.29% in AES-pretreated groups, respectively. Meanwhile, combination therapy significantly reduced interleukin (IL)-1β and tumor necrosis factor (TNF)-α expressions compared to monotherapy (<i>p</i> < 0.05). Additionally, combination therapy prevented LPS-induced histological and mitochondrial abnormalities greater than separate drugs. Western blotting indicated that combination therapy significantly suppressed nucleotide-binding oligomerization domain (NOD)-like receptors-3 (NLRP-3) inflammasome compared to separate drugs (<i>p</i> < 0.05). Further, combination therapy significantly decreased the expression of signaling cascades, p38 mitogen-activated protein kinases (p38 MAPK), nuclear factor kappa B (NF-κB)-p65, and extracellular-regulated kinases 1/2 (ERK1/2) versus monotherapy (<i>p</i> < 0.05). Interestingly, combined pretreatment significantly downregulated high mobility group box-1 (HMGB1) by 72.93%, and toll-like receptor 4 (TLR4) by −0.93-fold versus 61.92%, −0.83-fold in CoQ10 and 38.67%, −0.70-fold in AES pretreatment, respectively. Our results showed for the first time that the enhanced anti-inflammatory effect of combined CoQ10 and AES pretreatment prevented LPS-induced ALI via suppression of NLRP-3 inflammasome through regulation of HMGB1/TLR4 signaling pathway and mitochondrial stabilization.

Efficacy of terpenoids in attenuating pulmonary edema in acute lung injury: A meta-analysis of animal studies

“…After reviewing all of the publications, 10 studies were excluded because of missing outcome data ( Ehrhart et al, 2000 ; Tawadros et al, 2007 ; Nader and Baraka, 2012 ; An et al, 2014 ; Wang et al, 2015 ; Liu and Chen, 2016 ; Shen et al, 2017 ; Ni et al, 2019 ; Wang et al, 2019 ; Yang et al, 2019 ), and another 12 studies were excluded because multiple interventions were investigated ( Murakami et al, 2000 ; Lin et al, 2011 ; Li et al, 2014b ; Li et al, 2016a ; Li et al, 2016b ; Baradaran Rahimi et al, 2019 ; Ye et al, 2019 ; Duan et al, 2020 ; Yue et al, 2020 ; Choi et al, 2021 ; Zhang et al, 2021 ; Liu et al, 2022 ). In conclusion, 16 studies were included in this meta-analysis, as described below ( Shi et al, 2007 ; Yang et al, 2011 ; Chen et al, 2014 ; Yang et al, 2014 ; Yuan et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ; Ren et al, 2019 ; Zhang et al, 2020 ; Ali et al, 2021 ; Dikmen et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ) ( Figure 1 ).…”

“…Rats ranged in age from 6 to 8 weeks and in weight from 90 to 350 g. In terms of intervention, diterpenoid, monoterpenoid, sesquiterpenoid, and triterpenoid were used in seven studies ( Shi et al, 2007 ; Yang et al, 2011 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ), three studies ( Yuan et al, 2014 ; Ren et al, 2019 ; Li et al, 2021 ), two studies ( Ali et al, 2021 ; Wang et al, 2021 ), and four studies ( Chen et al, 2014 ; Zhang et al, 2020 ; Dikmen et al, 2021 ; Wu et al, 2021 ), respectively. In addition, 13 studies used male rats ( Shi et al, 2007 ; Yang et al, 2011 ; Chen et al, 2014 ; Yang et al, 2014 ; Yuan et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Luo et al, 2019 ; Ren et al, 2019 ; Zhang et al, 2020 ; Dikmen et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ), whereas three studies did not report gender ( Li et al, 2018b ; Ali et al, 2021 ; Wu et al, 2021 ). Sprague Dawley rats were used in 11 studies ( Shi et al, 2007 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ; Ren et al, 2019 ; Ali et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ) and Wistar rats in five studies ( Yang et al, 2011 ; Chen et al, 2014 ; Yuan et al, 2014 ; Zhang et al, 2020 ; Dikmen et al, 2021 ).…”

“…In addition, 13 studies used male rats ( Shi et al, 2007 ; Yang et al, 2011 ; Chen et al, 2014 ; Yang et al, 2014 ; Yuan et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Luo et al, 2019 ; Ren et al, 2019 ; Zhang et al, 2020 ; Dikmen et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ), whereas three studies did not report gender ( Li et al, 2018b ; Ali et al, 2021 ; Wu et al, 2021 ). Sprague Dawley rats were used in 11 studies ( Shi et al, 2007 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ; Ren et al, 2019 ; Ali et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ) and Wistar rats in five studies ( Yang et al, 2011 ; Chen et al, 2014 ; Yuan et al, 2014 ; Zhang et al, 2020 ; Dikmen et al, 2021 ).…”

“…LPS was administered intravenously in seven studies ( Yang et al, 2011 ; Yang et al, 2014 ; Wei and Wang, 2017 ; Li et al, 2018a ; Li et al, 2018b ; Luo et al, 2019 ; Dikmen et al, 2021 ), intraperitoneally in one study ( Shi et al, 2007 ), and intratracheally in eight studies ( Chen et al, 2014 ; Yuan et al, 2014 ; Ren et al, 2019 ; Zhang et al, 2020 ; Ali et al, 2021 ; Li et al, 2021 ; Wang et al, 2021 ; Wu et al, 2021 ). The LPS dosage ranged from 0.1 to 10 mg/kg.…”

Effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with ventilator-induced lung injury

“…It is found that the p38 mitogen-activated protein kinase (MAPK) signaling pathway is closely related to the lung injury [10][11][12] . This study was designed to investigate the effects of propofol on inflammatory response and activation of p38 MAPK signaling pathway in rats with VALI.…”