24 research outputs found
Role of host genetics in fibrosis
Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function
Effect of febuxostat on renal function in patients from South China with CKD3 diabetic nephropathy
Garlic Powder Effect on Plasma Renin Activity, and Cardiovascular Effects of Intravenous Angiotensin I and Angiotensin II in Normotensive and Hypertensive Male Rats
The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin
Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro
Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial
The relationship between apoptosis, chromatin configuration, histone modification and competence of oocytes: A study using the mouse ovary-holding stress model
Multifactorial Comparative Proteomic Study of Cytochrome P450 2E1 Function in Chronic Alcohol Administration
Differential relevance of NF-ÎșB and JNK in the pathophysiology of hemorrhage/resususcitation-induced liver injury after chronic ethanol feeding
Background: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-ÎșB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection.
Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested.
Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-ÎșB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-ÎșB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-ÎșB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-ÎșB phosphorylation after H/R.
Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-ÎșB