Role of Thymoquinone in Cardiac Damage Caused by Sepsis from BALB/c Mice

Li, Hongyang; Sun, Yan; Zhang, Ying; Guang, Yang; Guo, Lipeng; Zhao, Yue; Pei, Zuowei

doi:10.1007/s10753-018-0909-1

Cited by 22 publications

(26 citation statements)

References 43 publications

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“…Wan et al (36) demonstrated that the expression of autophagy-associated proteins, including beclin 1, declined to basal levels by 12 h post-CLP. Liu et al (39) revealed that TQ increased beclin 1 gene and protein expression levels; this result was in accordance with the results of the present study. However, high p62 aggregation in the LT was observed in the CLP group compared with in the control group.…”

Section: Discussionsupporting

confidence: 93%

Protective role of thymoquinone in sepsis‑induced liver injury in BALB/c mice

et al. 2019

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Sepsis increases the risk of developing liver injury. Previous studies have demonstrated that thymoquinone (TQ) exhibits hepatoprotective properties in vivo as well as in vitro . The present study aimed to investigate the underlying mechanisms of the protective effects of TQ against liver injury in septic BALB/c mice. Male BALB/c mice (age, 8 weeks) were randomly divided into four groups, namely, the control, TQ (50 mg/kg/day) treatment, cecal ligation and puncture (CLP), and TQ + CLP groups. CLP was performed following gavage of TQ for 2 weeks. At 48 h post-CLP, the histopathological alterations in the liver tissue (LT) and plasma levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed. The present study evaluated microtubule-associated protein light chain 3 (LC3), sequestosome-1 (p62) and beclin 1 protein expression by western blotting and immunostaining , as well as interleukin (IL)-6, IL-1β, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) mRNA expression by RT-qPCR. The results of the present study indicated that administration of TQ to mice reduced the histological alterations caused by CLP in LT. TQ inhibited the plasma levels of ALT, AST and ALP in the CLP group. TQ significantly inhibited the elevation of p62, IL-1β, IL-6, MCP-1 and TNF-α levels as well as increased the LC3, beclin 1 and IL-10 levels in LT. PI3K expression in the TQ + CLP group was significantly decreased compared with that in the CLP group. TQ treatment effectively modulated the expression levels of p62, LC3, beclin 1, PI3K and proinflammatory cytokines, and may be an important agent for the treatment of sepsis-induced liver injury.

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Section: Discussionsupporting

confidence: 93%

Protective role of thymoquinone in sepsis‑induced liver injury in BALB/c mice

et al. 2019

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“…Sepsis, which is a common complication of severe trauma, infection, shock and other stress states, has high incidence and high mortality rates (17). Sepsis-associated mortality is closely associated with damage, which can easily lead to multiple organ dysfunction, particularly heart damage (18). Therefore, it is necessary to examine the pathological mechanism of sepsis-induced myocardial injury in order to identify an effective therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction

et al. 2019

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Myocardial injury is one of the main symptoms of sepsis. However, the mechanisms underlying sepsis-induced myocardial dysfunction remain unclear. In the present study, the concentration of cardiac troponin T (CTnT) in serum was measured using an enzyme-linked immunosorbent assay kit. The levels of interleukin (IL)-1β and IL-18 were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis and the level of malondialdehyde (MDA) was determined using a corresponding kit. Myocardial pathology was analyzed via hematoxylin and eosin staining. RT-qPCR analysis and western blotting and/or immunohistochemistry were used to quantify the expression levels of thioredoxin-interacting protein (TNXIP), NOD-like receptor pyrin domain containing 3 (NLRP3), cleaved caspase-1, caspase-1, catalase and manganese-superoxide dismutase (MnSOD). The viability of cells was determined using a cell counting kit-8. Apoptosis and reactive oxygen species (ROS) were examined using flow cytometry. Models of sepsis-induced myocardial injury were successfully established; evidence included increases in the levels of CTnT, IL-1β, IL-18 and MDA and myocardial tissue damage in vivo , and decreased cell viability and improvements in IL-1β and IL-18 in vitro . The levels of TXNIP, NLRP3 and cleaved caspase-1 were upregulated in the sepsis models. Small interfering RNA targeting TNXNIP (siTXNIP) increased cell viability, reduced the apoptotic rate and attenuated the release of IL-1β and IL-18. The levels of TXNIP, NLRP3 and cleaved caspase-1 and production of ROS were suppressed by siTXNIP, accompanied by increases in catalase and MnSOD. TXNIP/NLRP3 serves an important role in the development of sepsis-induced myocardial damage.

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“…In addition, TQ alleviates diabetes-associated oxidative stress in cardiac tissues [ 12 ]. Furthermore, several studies have shown that the protective effect of TQ against cardiac damage, such as in cases of ischemic damage [ 13 ] and acute abdominal aortic ischemia-reperfusion injury [ 14 ], is mediated via the pyroptosis pathway [ 15 ]. Recently, pyroptosis, an inflammatory form of programmed cell death [ 16 ], has been gaining increasing attention, especially in relation to hyperlipidemia [ 17 , 18 ]; however, the pathophysiological mechanisms underlying the relationship between hyperlipidemia and cardiac damage are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Thymoquinone Protects against Hyperlipidemia-Induced Cardiac Damage in Low-Density Lipoprotein Receptor-Deficient (LDL-R-/-) Mice via Its Anti-inflammatory and Antipyroptotic Effects

Pei

Guo

Zhu

et al. 2020

BioMed Research International

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Hyperlipidemia is a risk factor for cardiac damage and cardiovascular disease. Increasing evidence has shown that dyslipidemia-related cardiac damage is associated with lipid accumulation, oxidative stress, and inflammation. Thymoquinone (TQ) is the major constituent of Nigella sativa, commonly known as black seed or black cumin, and is globally used in folk (herbal) medicine for treating and preventing a number of diseases and conditions. Several studies have shown that TQ can protect against cardiac damage. This study is aimed at investigating the possible protective effects of TQ on hyperlipidemia-induced cardiac damage in low-density lipoprotein receptor-deficient (LDL-R-/-) mice. Eight-week-old male LDL-R-/- mice were randomly divided into normal diet (ND), high-fat diet (HFD), and HFD and TQ (HFD+TQ) groups and were fed the different diets for eight weeks. Blood samples were obtained from the inferior vena cava in serum tubes and stored at -80°C until use. Some cardiac tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the cardiac tissues was snap-frozen in liquid nitrogen for mRNA preparation or immunoblotting. The levels of metabolism-related factors, such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP), were decreased in the HFD+TQ group compared with those in the HFD group. Periodic acid-Schiff staining demonstrated that lipid deposition was lower in the HFD+TQ group than in the HFD group. The expression of pyroptosis indicators (NOD-like receptor 3 (NLRP3), interleukin- (IL-) 1β, IL-18, and caspase-1), proinflammatory factors (IL-6 and tumor necrosis factor alpha (TNF-α)), and macrophage markers (cluster of differentiation (CD) 68) was significantly downregulated in the HFD+TQ group compared with that in the HFD group. Our results indicate that TQ may serve as a potential therapeutic agent for hyperlipidemia-induced cardiac damage.

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Role of Thymoquinone in Cardiac Damage Caused by Sepsis from BALB/c Mice

Cited by 22 publications

References 43 publications

Protective role of thymoquinone in sepsis‑induced liver injury in BALB/c mice

Protective role of thymoquinone in sepsis‑induced liver injury in BALB/c mice

Role of TXNIP/NLRP3 in sepsis-induced myocardial dysfunction

Thymoquinone Protects against Hyperlipidemia-Induced Cardiac Damage in Low-Density Lipoprotein Receptor-Deficient (LDL-R-/-) Mice via Its Anti-inflammatory and Antipyroptotic Effects

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