ABSTRACT
We previously demonstrated that there are acute and delayed phases of renal protection against renal ischemia and reperfusion (IR) injury with renal ischemic preconditioning (IPC). This study assessed whether hepatic IPC could also reduce distant renal IR injury through the blood stream-mediated supply of reactive oxygen species (ROS). Male C57BL/6 mice were randomly divided into four groups: group I, sham operated including right nephrectomy; group II (IR), left renal ischemia for 30 min and reperfusion injury; group III (IPC-IR), hepatic ischemia for 10 min followed by 10 min of reperfusion before left renal IR injury; group IV (MPG - IPC + IR), pretreated with 100 mg/kg N-(2-mercaptopropionyl)-glycine (MPG) 15 min before hepatic IPC and left renal IR injury. Renal function, histopathologic findings, proinflammatory cytokines, and cytoprotective proteins were evaluated 15 min or 24 hr after reperfusion. Hepatic IPC attenuated the expression of proinflammatory cytokines, tumor necrosis factor alpha, intercellular adhesion molecule 1, and induced inducible nitric-oxide synthase, and the phosphorylation of Akt in the murine kidney. Renal function was better preserved in mice with hepatic IPC (group III) than groups II or IV. Hepatic IPC protects against distant renal IR injury through the blood stream-delivery of hepatic IPC-induced ROS, by inducing cytoprotective proteins, and by inhibiting inflammatory reactions.
Subject(s)
Animals , Male , Mice , Intercellular Adhesion Molecule-1/genetics , Ischemic Preconditioning , Kidney/drug effects , Liver/blood supply , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Reactive Oxygen Species/metabolism , Reperfusion Injury/metabolism , Tiopronin/pharmacology , Tumor Necrosis Factor-alpha/geneticsABSTRACT
As doenças cardiovasculares representam a principal causa de morbi-mortalidade da atualidade, sendo a doença arterial coronariana seu maior expoente...
Subject(s)
Animals , Dogs , Myocardial Infarction/physiopathology , Disease Models, Animal , Antioxidants/therapeutic use , Dogs , Ischemia/therapy , Myocardial Reperfusion/methods , Tiopronin/pharmacologyABSTRACT
Sulfur is an essential element for the entire biological kingdom because of its incorporation into amino acids, proteins and other biomolecules. Sulfur atoms are also important in the iron-containing flavoenzymes. Unlike humans, plants can use inorganic sulfur to synthesize sulfur-containing amino acids. Therefore, plants are an important source of sulfur for humans. Sulfur-containing compounds are found in all body cells and are indispensable for life. Some of sulfur-containing antioxidant compounds are, cysteine, methionine, taurine, glutathione, lipoic acid, mercaptopropionylglycine, N-acetylcysteine, and the three major organosulfur compounds of garlic oil, diallylsulfide, diallyldisulfide and diallyltrisulfide. In a comparison of the structure-function relationship among these sulfur-containing antioxidant compounds, dihydrolipoic acid (the reduced form of LA) is the most effective antioxidant. Dihydrolipoic acid contains two sulfhydryl groups and can undergo further oxidation reaction to form lipoic acid. The antioxidative activities of sulfur-containing compounds follow a general trend, the more highly reduced forms are stronger antioxidants and the number of sulfur atoms determine, at least in part, their modulatory activites on the glutathione related antioxidant enzymes. In this article, the antioxidant effects and the antioxidative activities, of sulfur-containing amino acids, are reviewed. In addition, the general antioxidant effects and the structure-function relationship of some sulfur-containing compounds are also reviewed.
Subject(s)
Acetylcysteine/pharmacology , Amino Acids, Sulfur/pharmacology , Antioxidants/pharmacology , Cysteine/pharmacology , Glutathione/pharmacology , Methionine/pharmacology , Structure-Activity Relationship , Taurine/pharmacology , Thioctic Acid/pharmacology , Tiopronin/pharmacologyABSTRACT
Protective efficacy of MPG (2-mercaptopropionyl glycine) was studied against the toxic effects of lead acetate in Swiss albino mice. The animals were treated with single dose of lead acetate @ 180, 200 and 250 mg/kg b.wt. in presence and absence of MPG. The results indicated that the body weight was slightly higher in MPG treated groups on day 10 as compared to only respective lead treated groups in all the three dose level. However, significantly lower body weight was observed in both lead treated and lead along with MPG treated groups as compared to control. Patten of mortality is similar in both lead treated and lead plus MPG treated groups. Conspicuous degenerative changes in testicular tissues and elevation in sperm head shape abnormality were observed in both lead treated and lead along with MPG treated groups but the sperm head shape abnormality and damage were more in lead treated groups as compared to lead plus MPG treated groups. But this difference was non-significant between the two groups. These observations suggest that MPG may not be significantly effective against lead induced damage in testicular tissues at cellular level. However, MPG is able to maintain slightly lower level of sperm abnormality in all the three dose level as compared to their respective lead treated groups. Further, studies are needed to find out the optimum dose of MPG for protection against the lower doses of lead induced lethality as MPG is not significantly effective against the higher doses of lead.
Subject(s)
Animals , Body Weight , Dose-Response Relationship, Drug , Infusions, Parenteral , Male , Mice , Organometallic Compounds/toxicity , Spermatogenesis/drug effects , Spermatozoa/abnormalities , Testis/drug effects , Tiopronin/pharmacologyABSTRACT
Cyclophosphamide induced a depletion in liver glutathione (GSH) and high rate of lipid peroxidation. GSH depletion was evident from 20 min onwards and the maximum depletion was observed at 3 hr post treatment. Lipid peroxidation was significant only after the maximum depletion of GSH. Pretreatment with either MPG or WR-77913 individually, or in combination could prevent the depletion of GSH and induction of lipid peroxidation after cyclophosphamide treatment.
Subject(s)
Amifostine/analogs & derivatives , Animals , Cyclophosphamide/antagonists & inhibitors , Female , Glutathione/metabolism , Lipid Peroxidation/drug effects , Male , Mice , Tiopronin/pharmacologyABSTRACT
Adult female Swiss albino mice were exposed to 0.6, 1.2 and 2.4 Gy of 60Co gamma radiations in presence and absence of MPG. Quantitative studies were done in serial sections of ovary at 1, 3, 5, 7, 14 and 35 days after exposure. Primary follicles were found to be most radiosensitive. The depletion in the various types of follicles was checked to some extent by prior administration of MPG, but MPG could not prevent the complete elimination of all types of follicles by the last autopsy interval studied.