ABSTRACT
We studied the reparative and antioxidant effects of Thymogen and its new structural analogues obtained by binding amino acid D-Ala to the N- or C-end of the peptide molecule in acute toxic hepatopathy. Intragastric administration of carbon tetrachloride for 5 days caused the development of fat degeneration of hepatocytes, a decrease in catalase activity, and an increase in malondialdehyde concentration. Administration of peptides suppressed oxidative peroxidation and stimulated reparative regeneration of hepatocytes; Thymogen analogues produced more pronounced hepatotropic and antioxidant effects than Thymogen. Inclusion of D-Ala enhanced the effect of Thymogen on the processes of regeneration in hepatocytes and the antioxidant effect under conditions of acute carbon tetrachloride hepatopathy. The highest efficiency was achieved when the amino acid was added to the C-end of the molecule.
Subject(s)
Antioxidants , Chemical and Drug Induced Liver Injury , Humans , Antioxidants/pharmacology , Antioxidants/metabolism , Carbon Tetrachloride/toxicity , Liver/metabolism , Lipid Peroxidation , Peptides/pharmacology , Adjuvants, Immunologic/pharmacology , Models, Theoretical , Amino Acids/pharmacology , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolismABSTRACT
We studied the influence of synthetic indolicidin analogues on the development of acute periodontitis. The corrective effect was found in indolicidin analogues Nos. 7 and 8; it manifested in a decrease in the edema of gingival epithelium and lamina propria, a decrease in the relative area of inflammatory infiltrates, and a significant increase in the relative area of normal connective tissue. These changes were revealed as soon as on day 14 and were most pronounced in 21 days after the removal of the ligature. Indolicidin analogues Nos. 7 and 8 demonstrated similar effectiveness on the model of acute periodontitis.
Subject(s)
Antimicrobial Cationic Peptides/therapeutic use , Periodontitis/drug therapy , Animals , Antimicrobial Cationic Peptides/chemistry , Connective Tissue/drug effects , Connective Tissue/metabolism , Gingiva/cytology , Gingiva/metabolism , Mucous Membrane/drug effects , Mucous Membrane/metabolism , Rats, WistarABSTRACT
The effects of natural polyphenols, resveratrol (RES) and dihydroquercetin (DHQ), included in phospholipid nanoparticles, have been compared with free substances of RES and DHQ in in vitro and in vivo experiments. Preincubation of healthy donor plasma low density lipoproteins (LDL) with RES or DHQ included in phospholipid nanoparticles caused a more pronounced decrease in Cu2+ induced lipid oxidation compared with the free substances, and reduced the formation of lipid peroxides products. Bioavailabilities of RES and DHQ in phospholipid formulations after oral administration in rats were increased by 1.5-2 times. In an acute hypoxia model in mice prophylactic two-week administration of RES or DHQ phospholipid formulations resulted in 25% increase in survival and 1.5-fold increase in catalase activity in brain homogenates compared to free substances. Using the model of endothelial dysfunction in rats induced by L-NAME it was shown, that RES markedly attenuated the inhibition effect of L-NAME on NO synthesis. RES in phospholipid nanoparticles had the same action at a dose 10 times lower compared to free RES. Load test with resistance (clamping of the ascending aorta for 30 sec) showed that phospholipid formulation of RES possessed more pronounced protective effect due to the stimulation of endothelial NO-synthase.
Subject(s)
Antioxidants/pharmacology , Nanoparticles/chemistry , Phospholipids/chemistry , Quercetin/analogs & derivatives , Stilbenes/pharmacology , Alkenes/antagonists & inhibitors , Alkenes/metabolism , Animals , Antioxidants/chemistry , Antioxidants/pharmacokinetics , Drug Carriers , Humans , Lipid Metabolism/drug effects , Lipoproteins, LDL/chemistry , Male , Mice , NG-Nitroarginine Methyl Ester/pharmacology , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Oxidation-Reduction , Oxidative Stress , Quercetin/chemistry , Quercetin/pharmacokinetics , Quercetin/pharmacology , Rats , Rats, Wistar , Resveratrol , Stilbenes/chemistry , Stilbenes/pharmacokineticsABSTRACT
Hepato- and endothelioprotective action of runihol and ademetionine in 66 male rats with liver disease induced by essential and second-line antituberculosis drugs in combination with alcohol were studied. One-directed affirmative action study drugs, shown to reduce the level of biochemical markers of cytolysis and cholestasis in conjunction with a significant reduction in symptoms of fatty, hyaline droplet and hydropic degeneration. In this runihol had a more pronounced anticytolitic effect, while under the influence of ademethionine the normalization endothelial dysfunction was established.
Subject(s)
Antitubercular Agents/toxicity , Endothelium/drug effects , Liver Diseases, Alcoholic/drug therapy , S-Adenosylmethionine/therapeutic use , Animals , Cholestasis/drug therapy , Endothelium/pathology , Hyalin/metabolism , Lipid Metabolism , Liver/drug effects , Liver/pathology , Liver Diseases, Alcoholic/prevention & control , Male , RatsABSTRACT
Modeling of NO deficiency by administration of L-NAME to rats led to the development of arterial hypertension and endothelial dysfunction. Pronounced endothelium and cardioprotective effects of impaza under these experimental conditions manifested more markedly during combined administration of the preparation with standard hypotensive preparations enalapril and losartan.
Subject(s)
Antibodies/therapeutic use , Enalapril/therapeutic use , Hypertension/drug therapy , Losartan/therapeutic use , Nitric Oxide/deficiency , Animals , Hypertension/chemically induced , Male , NG-Nitroarginine Methyl Ester/pharmacology , Rats , Rats, WistarABSTRACT
Experimental NO deficiency induced by L-NAME injection led to the development of arterial hypertension, endothelial dysfunction, and cardiomyocyte hypertrophy and reduced blood content of nitrates and nitrites. Impaza, NO donors, activators of NO-synthase, antioxidants, and antihypertensive preparations produced endothelium-protective effect of different degree.
Subject(s)
Antibodies/therapeutic use , Endothelium, Vascular/drug effects , Nitric Oxide/deficiency , Animals , Antihypertensive Agents/therapeutic use , Antioxidants/therapeutic use , Hypertension/chemically induced , Hypertension/drug therapy , Male , NG-Nitroarginine Methyl Ester/pharmacology , Nitrates/metabolism , Nitric Oxide Donors/therapeutic use , Nitrites/metabolism , Rats , Rats, Wistar , Resveratrol , Stilbenes/therapeutic useABSTRACT
We studied the effects of antioxidants resveratrol and pQ510 on physiological parameters and the state of endothelial NO-synthase as a marker of the regulatory function of the endothelium in the aorta of rats with modeled arterial hypertension. The antioxidants promoted recovery of stable NO metabolites in rat serum and maintained expression of endothelial NO-synthase at a normal level. These effects were confirmed by correction of blood pressure and endothelium-dependent vascular dilation assessed by endothelial dysfunction coefficient.