losartan-potassium and Rhabdomyolysis

Erythropoietin (EPO) is a well-known hormone that is clinically used for the treatment of anemia. Very recently, an increasing body of evidence showed that EPO could still regulate bioactivities of macrophages. However, the details about the immunomodulatory effect of EPO on macrophages are not fully delineated, particularly in the setting of renal damages. Therefore, in the present study, we determined whether EPO could exert an impact on the dynamics of macrophages in a well-established model of rhabdomyolysis-induced acute kidney injury and explored the potential mechanisms. EPO was found to ameliorate kidney injuries by reducing macrophages recruitment and promoting phenotype switch toward M2 macrophages in vivo. It was also confirmed that EPO could directly suppress pro-inflammatory responses of M1 macrophages and promote M2 marker expression in vitro. Data indicated the possible involvement of Jak2/STAT3/STAT6 pathway in the augmentation of EPO on M2 polarization. These results improved the understanding of the immunoregulatory capacity of EPO on macrophages, which might optimize the therapeutic modalities of EPO.

Topics: Acute Kidney Injury; Animals; Erythropoietin; Janus Kinase 2; Macrophages; Mice; Rhabdomyolysis; Signal Transduction; STAT3 Transcription Factor; STAT6 Transcription Factor

Topics: Acute Kidney Injury; Animals; Erythropoietin; Male; Rhabdomyolysis

Rhabdomyolysis is one of the causes of acute renal failure. Erythropoietin (EPO) has been found to interact with its receptor (EPO-R) expressed in a large variety of non-haematopoietic tissues to induce a range of pleiotropic cytoprotective actions. In this study, we used recombinant human erythropoietin (rhEPO) to study the effects on the glycerol-induced rhabdomyolysis with acute renal failure in rats.. Twenty-four rats were divided into three groups as glycerol group, glycerol+EPO group and normal saline+EPO group. Rhabdomyolysis was induced by intramuscular injection of 10 mlkg(-1) 50% glycerol in rats. Ten minutes later, the rats received an intravenous injection of rhEPO (300 Ukg(-1)). Biochemical substances, including haemoglobin, blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and creatine phosphokinase (CPK), were measured at 0, 1, 3, 6, 9, 12, 18, 24 and 48 h. Rats were sacrificed 48 h later after glycerol administration and the kidneys were removed immediately for pathology and immunohistochemistry (IHC).. Intramuscular injection of glycerol significantly increased blood BUN, Cre, GOT, GPT and CPK levels and induced severe histopathologic damage in the kidneys. Nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) were increased and E-cadherin was decreased after glycerol administration, as detected by IHC in the kidneys. Post-treatment with rhEPO decreased blood BUN, Cre, GOT, GPT and CPK levels, decreased markers of kidney injury and suppressed the release of NF-κB and iNOS after rhabdomyolysis.. Treatment with rhEPO suppressed the activities of NF-κB and iNOS, decreased BUN, Cre, GOT, GPT and CPK levels, and decreased the markers of kidney injury after rhabdomyolysis. These actions ameliorated rhabdomyolysis-induced acute renal failure in rats.

Topics: Acute Kidney Injury; Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Urea Nitrogen; Erythropoietin; Glycerol; Immunohistochemistry; Injections, Intravenous; Kidney; Male; NF-kappa B; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Rhabdomyolysis; Tumor Necrosis Factor-alpha

Oxidative stress-related renal pathologies apparently include rhabdomyolysis and ischemia/reperfusion phenomenon. These two pathologies were chosen for study in order to develop a proper strategy for protection of the kidney. Mitochondria were found to be a key player in these pathologies, being both the source and the target for excessive production of reactive oxygen species (ROS). A mitochondria-targeted compound which is a conjugate of a positively charged rhodamine molecule with plastoquinone (SkQR1) was found to rescue the kidney from the deleterious effect of both pathologies. Intraperitoneal injection of SkQR1 before the onset of pathology not only normalized the level of ROS and lipid peroxidized products in kidney mitochondria but also decreased the level of cytochrome c in the blood, restored normal renal excretory function and significantly lowered mortality among animals having a single kidney exposed to ischemia/reperfusion. The SkQR1-derivative missing plastoquinone (C12R1) possessed some, although limited nephroprotective properties and enhanced animal survival after ischemia/reperfusion. SkQR1 was found to induce some elements of nephroprotective pathways providing ischemic tolerance such as an increase in erythropoietin levels and phosphorylation of glycogen synthase kinase 3β in the kidney. SkQR1 also normalized renal erythropoietin level lowered after kidney ischemia/reperfusion and injection of a well-known nephrotoxic agent gentamicin.

Topics: Animals; Antioxidants; Blotting, Western; Cells, Cultured; Erythropoietin; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Kidney; Kidney Diseases; Male; Microscopy, Confocal; Mitochondria; Molecular Structure; Oxidative Stress; Phosphorylation; Plastoquinone; Protective Agents; Rats; Reperfusion Injury; Rhabdomyolysis; Rhodamines; Survival Rate