ABSTRACT
Chronic kidney disease (CKD) or acute kidney injury (AKI) causes impaired kidney function, leading to cognitive impairment, neuropathy, and cerebrovascular disease. Due to kidney damage, toxins stay in the blood rather than leaving the body through the urine, and brain function is affected by kidney-brain interaction. The present study aimed to investigate the protective effects of erythropoietin mimetic peptide (pHBSP) and infliximab on ischemic renal reperfusion injury. The experiment was performed on 70 white male Wistar laboratory rats which received recombinant erythropoietin, pHBSP, and infliximab. Under anesthesia, traumatic vascular clamps were applied to the left renal pedicle for 40 min, and nephrectomy was performed on the right. Functional tests and laboratory tests were performed 5 min and 24 h after the reperfusion. Thereafter, 24 h after the surgery, the plasma creatinine and urea levels in the sham-operated animals were obtained at 45.9±0.8 mmol/L and 6.7±0.2 mmol/L, respectively. Plasma creatinine and urea levels in the control group animals were 102.63±3.6 mmol/L and 21.80±1.29 mmol/L, respectively. The administration of pHBSP and infliximab to the animals with ischemia-reperfusion kidney injury has a pronounced nephroprotective effect, as compared to erythropoietin. There was a significant decrease in blood levels of creatinine and urea, improvement of microcirculation in the kidney, normalization of glomerular filtration rate, and fractional sodium excretion. The results of the study demonstrated pointed to the prospects of pHBSP and infliximab administration in ischemia-reperfusion kidney injury and justified the feasibility of further research in this field.
Subject(s)
Erythropoietin , Reperfusion Injury , Animals , Male , Rats , Erythropoietin/pharmacology , Erythropoietin/therapeutic use , Infliximab/pharmacology , Infliximab/therapeutic use , Kidney/blood supply , Rats, Wistar , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & controlABSTRACT
We performed correction of endothelial dysfunction with phenol derivatives KUD-259 and KUD-974 containing heteroatomic and heterocyclic structures. Pharmacological activity of KUD-259 and KUD-974 surpassed that of L-norvaline, a non-selective arginase inhibitor.
Subject(s)
Arginase/antagonists & inhibitors , Phenol/chemistry , Thrombin/chemistry , Animals , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/pharmacology , Rats , Rats, Wistar , Signal Transduction/drug effects , Valine/analogs & derivatives , Valine/pharmacologyABSTRACT
The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed.
Subject(s)
Arginine/administration & dosage , Endothelium/drug effects , Hypertension/prevention & control , Placenta/drug effects , Pre-Eclampsia/drug therapy , Albuminuria/prevention & control , Animals , Arginine/therapeutic use , Blood Pressure/drug effects , Endothelium/physiology , Female , Humans , Injections, Intraperitoneal , Microcirculation/drug effects , Microcirculation/physiology , NG-Nitroarginine Methyl Ester/administration & dosage , NG-Nitroarginine Methyl Ester/adverse effects , Nitric Oxide Synthase Type III/metabolism , Placenta/blood supply , Pre-Eclampsia/chemically induced , Pre-Eclampsia/metabolism , Pregnancy , RatsABSTRACT
L-arginine (200 mg/kg), vitamin B(6) (2 mg/kg), and folic acid (0.2 mg/kg) exert a protective effect on endothelial function in L-NAME-induced NO deficiency in male and pregnant female Wistar rats. Combined administration of these agents effectively prevented the development of endothelial dysfunction and L-NAME-induced preeclampsia.
Subject(s)
Arginine/pharmacology , Endothelium/physiopathology , Folic Acid/pharmacology , Nitric Oxide/deficiency , Placenta/blood supply , Vitamin B 6/pharmacology , Animals , Arginine/therapeutic use , Drug Therapy, Combination , Endothelium/drug effects , Endothelium/metabolism , Female , Folic Acid/therapeutic use , Male , Microcirculation/drug effects , NG-Nitroarginine Methyl Ester , Nitric Oxide Synthase Type III/metabolism , Placenta/drug effects , Placenta/metabolism , Pre-Eclampsia/chemically induced , Pre-Eclampsia/drug therapy , Pre-Eclampsia/metabolism , Pregnancy , Rats , Rats, Wistar , Vitamin B 6/therapeutic useABSTRACT
Intragastric methionine (3 g/kg daily for 7 days) elevates homocysteine concentration and increases the endothelial dysfunction coefficient. This protocol of methionine treatment is an adequate model of hyperhomocysteine-induced endothelial dysfunction and can be used for studies of the endothelio- and cardioprotective effects of drugs.
Subject(s)
Endothelium, Vascular/pathology , Hyperhomocysteinemia/physiopathology , Vascular Diseases/physiopathology , Animals , Endothelium, Vascular/drug effects , Hyperhomocysteinemia/complications , Hyperhomocysteinemia/drug therapy , Methionine/therapeutic use , Rats , Vascular Diseases/drug therapy , Vascular Diseases/etiologyABSTRACT
Experiments on laboratory animals with nitric oxide deficiency modeled by the introduction of L-NAME (NO-synthase inhibitor) revealed the endothelio- and cardioprotective effects of clarithromycin, josamycin, roxithromycin, midecamycin and azythromycin. The administration of these macrolides leads to a decrease in the resulting area of the diagram of functional indices of the state of vessels and myocardium, which is approaching the corresponding area for intact animals.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Cardiotonic Agents/therapeutic use , Endothelium, Vascular/drug effects , Hypertension/physiopathology , Macrolides/therapeutic use , Nitric Oxide/deficiency , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Blood Pressure/drug effects , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/pharmacology , Disease Models, Animal , Endothelium, Vascular/physiology , Heart Function Tests , Hypertension/drug therapy , Hypertension/metabolism , Macrolides/administration & dosage , Macrolides/pharmacology , Male , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Rats, Wistar , Vasoconstriction/drug effectsABSTRACT
The cardioprotective and endothelioprotective effects of the macrolide antibiotics roxithromycin, azythromycin, and midecamycin have been studied on laboratory animals with models of the coronaro-occlusional myocardial infarction and endothelial dysfunction. The drugs led to a dose-dependent decrease in lethality, reduced the zone of necrosis of the left ventricle after coronary occlusion, and produced a positive effect on the functioning of endothelium.