scholarly journals Central blockade of TLR4 improves cardiac function and attenuates pro‐inflammatory cytokines and oxidative stress in hypertensive rats

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Rahul Babulal Dange ◽  
Deepmala Agarwal ◽  
Jorge Vila ◽  
Brad Wilson ◽  
Ryoichi Teruyama ◽  
...  
2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Deepmala Agarwal ◽  
Rahul B Dange ◽  
Joseph Francis

Although exercise has been recommended for the treatment of hypertension (HTN), the precise mechanisms of effects of exercise training (ExT) in HTN remain largely unexplored. Based on our recent unpublished results, here we tested the hypothesis that central increase in GSK-3β activity would cause reversal of effects of ExT in HTN. To increase GSK-3β activity in the brain, we chronically injected Triciribine (TCN) by intracerebroventricular (ICV) route. 90 Sprague-Dawley rats were randomized into six groups (n=15/group): 1) Sal+Ex+Veh; 2) Sal+Ex+TCN; 3) AngII+Sed+Veh; 4) AngII+Sed+TCN; 5) AngII+Ex+Veh; 6) AngII+Ex+TCN (Sal, saline; Ex, exercise; Veh, vehicle; Sed, sedentary). Rats were given AngII (hypertensive) or Veh (Normotensive) via osmotic minipumps. Groups 1, 2, 5, and 6 received moderate-intensity ExT for 42 days; groups 3 and 4 were sedentary. MAP was measured by radio-telemetry and cardiac function by echocardiography. The PVN tissues were examined for TNF, IL-1β, IL-10, and oxidative stress markers (iNOS, NOX2) levels. ExT delayed the progression of HTN, and improved cardiac hypertrophy and function in hypertensive rats. Chronic ICV infusion of TCN prevented these beneficial changes (Table). TCN prevented exercise-induced improvement in balance between pro- and anti-inflamamtory cytokines as well as exercise-induced reduction in oxidative stress within the PVN of hypertensive rats. These findings provide direct evidence that the beneficial effects of regular moderate-intensity ExT in HTN are mediated, at least in part, by reduced activation of central GSK-3β and potentially via improvement in inflammatory cytokines and oxidative stress within the PVN.


Author(s):  
Hany M.R. Abdel-Latif ◽  
Mahmoud A.O. Dawood ◽  
Samy F. Mahmoud ◽  
Mustafa Shukry ◽  
Ahmed E. Noreldin ◽  
...  

In the present study, fish were exposed to sub-lethal doses of CuONPs (68.92 ± 3.49 nm) (10, 20, and 50 mg/L) for a long exposure period (25 days). Compared to the control group (0.0 mg/L CuONPs), a significant dose-dependent elevation in blood urea and creatinine values, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase enzyme activities were evident in CuONPs-exposed groups (P < 0.05). Fish exposure to 50 mg/L CuONPs significantly upregulated the transcription of pro-inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin 12, and interleukin 8), heat shock protein 70, apoptosis-related gene (caspase 3), and oxidative stress-related (superoxide dismutase, catalase, and glutathione peroxidase) genes in liver and gills of the exposed fish in comparison with those in the control group (P < 0.05). Moreover, varying histopathological injuries were noticed in the hepatopancreatic tissues, posterior kidneys, and gills of fish groups correlated to the examined exposure dose of CuONPs. In summary, our results provide new insights and helpful information for better understanding the mechanisms of CuONPs toxicity in Nile tilapia at hematological, molecular levels, and tissue levels.


2015 ◽  
Vol 6 (10) ◽  
pp. 3296-3306 ◽  
Author(s):  
Xiao-Lin Yu ◽  
Ya-Nan Li ◽  
He Zhang ◽  
Ya-Jing Su ◽  
Wei-Wei Zhou ◽  
...  

Rutin inhibited amylin aggregation, amylin-induced neurocytotoxicity, and decreased the production of ROS, NO, GSSG, malondialdehyde and pro-inflammatory cytokines.


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