scholarly journals Protective Effect of Quercetin, a Flavonol against Benzo(a)pyrene-Induced Lung Injury via Inflammation, Oxidative Stress, Angiogenesis and Cyclooxygenase-2 Signalling Molecule

2021 ◽  
Vol 11 (18) ◽  
pp. 8675
Author(s):  
Mohammad A. Alzohairy ◽  
Amjad Ali Khan ◽  
Mohammad Azam Ansari ◽  
Ali Yousif Babiker ◽  
Mohammed A. Alsahli ◽  
...  

Quercetin (Qu) is an important polyphenolic flavonoid which exhibits tremendous antioxidant, anti-inflammatory and other health promoting effects. The aim of the current study was to explore the therapeutic role of Qu on benzo(a)pyrene [B(a)P]-induced lung injury in rats. B(a)P was given to the rats at dose of 50 mg/kg b.w. for continues 8 weeks through oral gavage. The rats were treated with Qu at dose of 50 mg/kg b.w prior 30 min before the oral administration of B(a)P. The effects of Qu were studied by measuring the level of lactate dehydrogenase (LDH), anti-oxidant enzymes, lipid peroxidation, inflammatory cytokines, lung tissues architecture and expression of cyclooxygenase-2 (COX-2). The level of pro‑inflammatory cytokines such as IL-1β (27.30 vs. 22.80 pg/mL), IL-6 (90.64 vs. 55.49 pg/mL) and TNF-α (56.64 vs. 40.49 pg/mL) increased significantly and antioxidant enzymes decreased significantly in benzopyrene-induced lung injury in comparison to the control group. The treatment with Qu potentially reversed the effects of B(a)P to a great extent, as it led to the enhancement of antioxidant enzymes and decreased proinflammatory cytokines level. A significant surge of VEGF level was noticed in the B(a)P group as compared to the control group, while the Qu treatment groups exhibited less angiogenesis as lower level of VEGF levels, compared with the B(a)P treatment group. The Qu treatment significantly decreased the degrees of histopathological changes and collagen deposition in B(a)P-induced lung injury. The B(a)P-treated group showed higher cytoplasmic expression of COX-2 protein, which significantly decreased in the Qu treatment group. These outcomes recommend an effective role of Qu in the protection of lung injury against B(a)P through the regulation of the inflammatory factors, oxidative stress and the maintenance lung tissue architecture.

Author(s):  
Hong Wang ◽  
Wenjuan Zhang ◽  
Jinren Liu ◽  
Junhong Gao ◽  
Le Fang ◽  
...  

Abstract Blast lung injury (BLI) is the major cause of death in explosion-derived shock waves; however, the mechanisms of BLI are not well understood. To identify the time-dependent manner of BLI, a model of lung injury of rats induced by shock waves was established by a fuel air explosive. The model was evaluated by hematoxylin and eosin staining and pathological score. The inflammation and oxidative stress of lung injury were also investigated. The pathological scores of rats’ lung injury at 2 h, 24 h, 3 days, and 7 days post-blast were 9.75±2.96, 13.00±1.85, 8.50±1.51, and 4.00±1.41, respectively, which were significantly increased compared with those in the control group (1.13±0.64; P<0.05). The respiratory frequency and pause were increased significantly, while minute expiratory volume, inspiratory time, and inspiratory peak flow rate were decreased in a time-dependent manner at 2 and 24 h post-blast compared with those in the control group. In addition, the expressions of inflammatory factors such as interleukin (IL)-6, IL-8, FosB, and NF-κB were increased significantly at 2 h and peaked at 24 h, which gradually decreased after 3 days and returned to normal in 2 weeks. The levels of total antioxidant capacity, total superoxide dismutase, and glutathione peroxidase were significantly decreased 24 h after the shock wave blast. Conversely, the malondialdehyde level reached the peak at 24 h. These results indicated that inflammatory and oxidative stress induced by shock waves changed significantly in a time-dependent manner, which may be the important factors and novel therapeutic targets for the treatment of BLI.


2019 ◽  
Vol 8 (5) ◽  
pp. 741-753 ◽  
Author(s):  
Israa F. Mosa ◽  
Mokhtar I. Yousef ◽  
Maher Kamel ◽  
Osama F. Mosa ◽  
Yasser Helmy

Abstract Hydroxyapatite nanoparticles (HAP-NPs) are an inorganic component of natural bone and are mainly used in the tissue engineering field due to their bioactivity, osteoconductivity, biocompatibility, non-inflammatory, and non-toxicity properties. However, the current toxicity data for HAP-NPs regarding human health are limited, and only a few results from basic studies have been published. Therefore, the present study was designed to investigate the beneficial role of chitosan nanoparticles (CsNPs) and curcumin nanoparticles (CurNPs) in alleviating nephrotoxicity induced by HAP-NPs in male rats. The results showed that HAP-NPs caused a reduction in antioxidant enzymes and induced lipid peroxidation, nitric oxide production and DNA oxidation. Moreover, HAP-NP administration was associated with intense histologic changes in kidney architecture and immunoreactivity to proliferating cell nuclear antigen (PCNA). However, the presence of CsNPs and/or CurNPs along with HAP-NPs reduced the levels of oxidative stress through improving the activities of antioxidant enzymes. Also, the rats administered the nanoparticles showed a moderate improvement in glomerular damage which matched that of the control group and showed mild positive reactions to PCNA–ir in glomeruli and renal tubules in the cortical and medullary portions. These novel insights confirm that the presence of chitosan and curcumin in nanoforms has powerful biological effects with enhanced bioactivity and bioavailability phenomena compared to their microphase counterparts. Also, they were able to ameliorate the nephrotoxicity induced by HAP-NPs.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Kunlun Huang ◽  
ChanMei Shi ◽  
JingQi Min ◽  
Laifu Li ◽  
Tao Zhu ◽  
...  

Background. Epidemiological studies have shown that exposure to PM induces oxidative stress, leading to a variety of health problems. In particular, PM2.5 contains a lot of substances harmful to the human body and penetrates into the lungs to induce lung injury. At the same time, there is increasing evidence that oxidative stress also affects the severity of lung injury. However, there is still no good way to reduce or eliminate these hazards. In the future, more experimental research is needed to further confirm the mechanisms of these hazards and formulate effective preventive measures and treatment plans for their hazard mechanisms. Curcumin has been reported to reduce oxidative stress and inflammatory damage and protect organs. Objective. To investigate whether curcumin can play a protective role against PM2.5-induced oxidative stress and inflammatory damage by inducing expression of the HO-1/CO/P38 MAPK pathway. Methods. In this experiment, PM2.5 was dropped into the trachea to establish a lung injury model in mice. 28 SPF-grade male Kunming mice were randomly divided into 4 groups: normal control group, saline control group, PM2.5 treatment group, and curcumin intervention group. Albumin (ALB), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were measured in alveolar lavage fluid (BALF) to assess lung tissue damage. Colorimetric detection of oxidative stress indicators such as MDA, GSH-PX, T-AOC, and CAT in the lung tissue was performed. The levels of IL-6 and TNF-α in the lung tissue were determined by ELISA. Histopathological examination was used for the assessment of alveolar epithelial damage. The protein expression of the HO-1/P38 MAPK pathway in the lung tissue was determined by Western blot and immunohistochemistry. Endogenous CO was detected by spectrophotometry. The results showed that the expression of the HO-1/CO/P38 MAPK protein in the lung tissue was significantly increased in the curcumin intervention group compared with the PM2.5 treatment group, and it was statistically significant (P<0.05). Compared with the PM2.5 treatment group, the curcumin intervention group can reduce the amount of ALB, LDH, and ALP in BALF; reduce the levels of MDA, IL-1, and TNF-α in the lung tissue; and improve GSH-PX, T-AOC, and CAT levels, but there is no statistical difference (P>0.05). Conclusion. We found that PM2.5 can cause lung damage through oxidative stress and inflammatory responses. Oxidative stress and inflammatory responses increase the expression of HO-1/CO/P38 MAPK. The intervention of curcumin can further increase the expression of HO-1/CO/P38 MAPK.


2002 ◽  
Vol 283 (5) ◽  
pp. G1166-G1174 ◽  
Author(s):  
Albert M. Song ◽  
Lakshmi Bhagat ◽  
Vijay P. Singh ◽  
Gijs G. D. Van Acker ◽  
Michael L. Steer ◽  
...  

Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important role in inflammation. We have studied the role of COX-2 in acute pancreatitis and pancreatitis-associated lung injury using both the pharmacological inhibition of COX-2 and genetic deletion of COX-2. Pancreatitis was induced in mice by 12 hourly injections of cerulein. The severity of pancreatitis was assessed by measuring serum amylase, pancreatic trypsin activity, intrapancreatic sequestration of neutrophils, and acinar cell necrosis. The severity of lung injury was evaluated by measuring lactate dehydrogenase levels in the bronchoalveolar lavage fluid and by quantitating neutrophil sequestration in the lung. In both the pharmacologically inhibited and genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was reduced compared with the noninhibited strains of COX-2-sufficient mice. This reduction in injury indicates that COX-2 plays an important proinflammatory role in pancreatitis and its associated lung injury. Our findings support the concept that COX-2 inhibitors may play a beneficial role in the prevention of acute pancreatitis or in the reduction of its severity.


2019 ◽  
Vol 20 (7) ◽  
pp. 1771
Author(s):  
Tzu-Hsiung Huang ◽  
Pin-Hui Fang ◽  
Jhy-Ming Li ◽  
Huan-Yuan Ling ◽  
Chieh-Mo Lin ◽  
...  

Mechanical ventilation is usually required for saving lives in critically ill patients; however, it can cause ventilator-induced lung injury (VILI). As VEGF-secreting Ly6Chigh monocytes are involved in VILI pathogenesis, we investigated whether cyclooxygenase-2 (COX-2) activity regulates the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI. The clinically relevant two-hit mouse model of VILI, which involves the intravenous injection of lipopolysaccharide prior to high tidal volume (HTV)-mechanical ventilation, was used in this study. To investigate the role of COX-2 in the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI, celecoxib, which is a clinical COX-2 inhibitor, was administered 1 h prior to HTV-mechanical ventilation. Pulmonary vascular permeability and leakage, inflammatory leukocyte infiltration, and lung oxygenation levels were measured to assess the severity of VILI. HTV-mechanical ventilation significantly increased the recruitment of COX-2-expressing Ly6Chigh, but not Ly6Clow, monocytes. Celecoxib significantly diminished the recruitment of Ly6Chigh monocytes, attenuated the levels of VEGF and total protein in bronchoalveolar lavage fluid, and restored pulmonary oxygenation during VILI. Our findings demonstrate that COX-2 activity is important in the recruitment of VEGF-secreting Ly6Chigh monocytes, which are involved in VILI pathogenesis, and indicate that the suppression of COX-2 activity might be a useful strategy in mitigating VILI.


Author(s):  
Shahin Kashefimehr ◽  
Mohammadreza Nasirzadeh

Introdution: Diabetes is the most common endocrine disorder characterized by hyperglycemia. Increasing the oxidative stress and changing the amount of antioxidants play important roles in pathogenesis of diabetes. Nowadays to control diabetes and its complications, the use of herbal drugs is considered widely. In this study, we investigated the effect of oleuropein on antioxidant enzymes activity of heart tissue in Streptozotocin induced diabetic male rats. Methods: In this study, 30 adult male Wistar rats with a weight range of 190±30 gr were randomly divided into 3 groups(n=10 in each group): 1) control group or intact rats, 2) diabetic rats, and 3) treatment group, which received 60 mg/kg oleuropein for 30 days by gastric gavage. Diabetes was induced by injection of streptozotocin (60 mg/kg) intraperitoneally. At the end of the treatment, serum concentrations of blood glucose and heart tissue antioxidant enzymes activity were determined. The obtained data were analyzed using  SPSS Inc., Chicago, IL; Version 18, statistical method of one way variance analysis and post hoc-Duncan test . Results: The results showed that serum concentration of glucose decrease significantly in treatment group compared with the diabetic group (p=0.000). Also, TAC, SOD and GPX activity increased significantly in the treatment group compared with the diabetic group (p=0.000). Conclusion: This study showed that oleuropein can prevent blood glucose increasing and reinforce antioxidant system of cardiac tissue in diabetic rats.


2016 ◽  
Vol 36 (4) ◽  
pp. 349-364 ◽  
Author(s):  
R Ali ◽  
A Shahid ◽  
N Ali ◽  
SK Hasan ◽  
F Majed ◽  
...  

Naringenin is a naturally occurring flavanones and has been found to exhibit free radical scavenging, enzyme inhibition, antioxidants, anti-inflammatory, and anticancer activities. Present study was designed to evaluate the protective role of naringenin against benzo[a]pyrene (B[a]P)-induced oxidative stress and pulmonary toxicity. Rats were treated with naringenin at a dose of 100 mg/kg body weight (b. wt.), by oral gavage. B[a]P in a single dose of 50 mg/kg b. wt. was given intraperitoneally. Total protein, total cell counts, lactate dehydrogenase, lipid peroxidation, reduced glutathione, antioxidant enzymes activities, lung histology and expression of nuclear factor kappa B (NF-κB), and cyclo-oxygenase-2 (COX-2) was assessed to evaluate protective effects of naringenin. Histopathological and immunohistochemical studies were also carried out to observe lung toxicity and inflammation. B[a]P administration enhanced the levels of lung injury markers and reduced antioxidant enzymes activities. Naringenin treatment attenuated the levels of oxidative stress by restoring antioxidant enzymes, further improved lung histological damage and significant decrease in inflammatory responses. Naringenin also effectively decreased the expression of NF-κB, and COX-2 induced by B[a]P. These findings suggest that naringenin supplementation is beneficial in maintaining the integrity of alveoli and the epithelium that may be used as a protective agent in B[a]P-induced oxidative stress and lung damage. However, further studies are warranted to elucidate the potential mechanism of action of naringenin.


2018 ◽  
Vol 46 (1) ◽  
pp. 8
Author(s):  
Mustafa Hitit ◽  
Orhan Corum ◽  
Duygu Durna Corum ◽  
Huseyin Donmez ◽  
Gul Cetin ◽  
...  

Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillateintraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes.Materials, Methods &amp; Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 geach) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groupsaccording to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP).Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene. The expression of manganese superoxide dismutase (MnSOD) mRNA was in a steady state level between the control group and group 2 (P &gt; 0.05); however, it significantly increased in group 3 and 4 compared with that in the control (P &lt; 0.05). Expression of catalase (CAT) mRNA was significantly higher in group 2 than in the control group (P &lt; 0.05) although it was lower in group 3 and 4 than in group 2 (P &lt; 0.05); however, it appeared to be similar among the control group, group 3, and group 4 (P &gt; 0.05). Copper (Cu) SOD mRNA was equallyexpressed in both the control group and group 2 (P &gt; 0.05) but was lower in group 3 and 4 than in group 2 (P &lt; 0.05). Expressions of HIF1A, HIF2A, and HIF3A mRNA were detected in the rat heart tissues in the control and 2, 4, and 8 h after administration of NO distillate. Expression ofHIF1A mRNA was in a steady state and did not differ among groups 2, 3, and 4 (P &gt; 0.05). Similarly, the expression of HIF2A mRNA did not change between the control group and group 2 (P &gt; 0.05); however, it was higher in group 3 than in the control (P &lt; 0.05) and tended to behigher in group 3 than in group 2 (P = 0.063). HIF3A mRNA expression did not change significantly in the heart tissue of any of the groups (P &gt; 0.05).Discussion: The present study using rats determined that MnSOD, CAT, CuSOD, HIF1A, HIF2A, and HIF3A mRNA are expressed in the heart tissues after administration of NO distillate. The increased expression of HIF2A mRNA after 4 h in accordance with a rise in CAT mRNA after 2 h, and MnSOD mRNA after 4 and 8 h might confirm the role of HIF2A mRNA in oxidative stress defense by regulating antioxidant enzymes; consequently, this study may expand our understanding of uses of NO distillate with respect to molecular pathways.


2020 ◽  
Vol 70 (2) ◽  
pp. 227-237
Author(s):  
Eda Güneş

Abstract The aim of the this study was to evaluate the effects of fresh, dried and freeze-dried Centaurea depressa M. Bieb. (Asteraceae) on the oxidant and antioxidant status of the model organism D. melanogaster Meigen (Diptera: Drosophilidae) experimentally. The study was carried out from 2016 to 2019, and plant leaf extracts (0-50 mg/l) were added to insect standard artificial diets. The total protein, protein carbonyl content and glutathione-S-transferase, superoxide dismutase and catalase activities were quantified at the insect’s third larval stage. Our data showed that protein carbonyl content varied from 2.70 nmol/mg protein in the control group to 59.11 nmol/mg protein in the group fed with fresh leaf extract signifying induction of oxidative stress. All extracts increased the levels of all antioxidant enzymes and decreased the amounts of total protein. Meanwhile, the group fed with the freeze-dried extract showed no significant difference in the levels of total protein and protein carbonyl content except at the 50 mg/l concentration of the extract. Moreover, this group had superoxide dismutase and catalase activities 4 to 5 times higher than in the control group. In conclusion, induction of oxidative stress indicates that the fresh form of C. depressa leaves may have potential as a natural pesticide, whereas induction of endogenous antioxidant enzymes by the freeze-dried extract suggest its potential as an antioxidant.


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