metallothionein and Ischemia

This study was performed to determine the effect of zinc supplementation effects on metallothionein levels in testis ischaemia-reperfusion of rats. The experimental groups were designed as Control, Sham, Ischaemia-Reperfusion (I/R) and I/R + Zinc supplemented. Zinc supplemented as 5 mg/kg day for 3 weeks. Testis tissues were analysed for metallothionein by immunohistochemical staining procedures. Group comparison showed that the zinc-supplemented ischaemia-reperfusion group had a significantly higher level of cells strongly stained with metallothionein than all other groups. A general evaluation of the results suggests that zinc supplementation is a strong stimulant of metallothionein synthesis in the ischaemic testis tissue.

Topics: Animals; Ischemia; Male; Metallothionein; Rats; Rats, Wistar; Testis; Zinc

We investigated how zinc (Zn) supplementation affects metallothionein levels in the cortex and medulla of ischemic renal tissue of rats. We used adult male rats divided into four groups: group 1, untreated control; group 2, sham-operated; group 3, ischemia-reperfusion; group 4, ischemia-reperfusion + 5 g/kg Zn. Renal tissue was analyzed using immunostaining of rat metallothionein. Cells stained with metallothionein were counted and their percentage was calculated. We found that the Zn supplemented ischemia and reperfusion group exhibited a greater percentage of cells stained strongly for metallothionein in the renal cortex than all other groups. In the renal medulla, percentages of weak staining for metallothionein in the control and ischemia and reperfusion groups were greater than those in the sham and Zn-supplemented ischemia/reperfusion groups. Our findings indicate that the main effect of Zn in the renal tissue occurs in the cortex, while metallothionein synthesis in the renal medulla is unaffected.

Topics: Animals; Dietary Supplements; Ischemia; Kidney Diseases; Male; Metallothionein; Random Allocation; Rats; Rats, Wistar; Zinc Sulfate

Topics: Animals; Blotting, Western; Cell Survival; Chemokine CXCL12; Diabetes Mellitus, Experimental; Endothelial Progenitor Cells; Enzyme-Linked Immunosorbent Assay; Female; Hindlimb; Hypoxia-Inducible Factor 1, alpha Subunit; Ischemia; Leukocytes, Mononuclear; Male; Metallothionein; Mice; Neovascularization, Pathologic; Oxidative Stress; RNA, Small Interfering; Vascular Endothelial Growth Factor A

We have investigated the effect of benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke and an agonist for the aryl hydrocarbon receptor (AHR), on hypoxia-induced angiogenesis. Ischemia was induced by femoral artery ligation in wild-type and AHR-null mice, and the animals were subjected to oral administration of B[a]P (125 mg/kg) once a week. Exposure to B[a]P up-regulated the expression of metallothionein in the ischemic hindlimb and markedly inhibited ischemia-induced angiogenesis in wild-type mice. The amounts of interleukin-6 and of vascular endothelial growth factor (VEGF) mRNA in the ischemic hindlimb of wild-type mice were reduced by exposure to B[a]P. These various effects of B[a]P were markedly attenuated in AHR-null mice. Our observations suggest that the loss of the inhibitory effect of B[a]P on ischemia-induced angiogenesis apparent in AHR-null mice may be attributable to maintenance of interleukin-6 expression and consequent promotion of angiogenesis through up-regulation of VEGF expression.

Topics: Angiotensin I; Animals; Aryl Hydrocarbon Receptor Nuclear Translocator; Benzo(a)pyrene; Carcinogens; Cytochrome P-450 CYP1A1; Femoral Artery; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; Ischemia; Lower Extremity; Male; Metallothionein; Mice; Mice, Inbred Strains; Neovascularization, Physiologic; Receptors, Angiotensin; Receptors, Aryl Hydrocarbon; Receptors, Vascular Endothelial Growth Factor; Up-Regulation; Vascular Endothelial Growth Factor A

To investigate the effect of liposome-carried metallothionein (lipo-MT) on secondary ischemia-reperfusion injury in the rat island flap.. An abdominal island flap was created in the Wistar rat. The animals were divided into four groups: the sham group, the secondary ischemia-reperfusion group, the group treated with blank liposome and the group treated with lipo-MT. The malondialdehyde (MDA) content, the myeloperoxidase (MPO) activity was assayed immediately, at 30 minutes and 7 days after the secondary venous ischemia-reperfusion. The level of endothelin (ET) and lactic dehydrogenase (LDH) of the rat plasma was measured at 30 minutes after secondary venous ischemia-reperfusion. The content of MT of the flap was assayed by Cd-hemoglobin saturation method at 7 days after the operation.. The treatment of lipo-MT significantly decreased the content of MDA, MPO of the flap, decreased the activity of ET, LDH of the rat palsma, increased the content of MT of the flap and improved the flap viability.. Lipo-MT can improve flap survival by reducing ischemia-reperfusion injury.

Topics: Animals; Endothelins; Graft Survival; Ischemia; Lactate Dehydrogenases; Liposomes; Malondialdehyde; Metallothionein; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Surgical Flaps; Time Factors

Metallothionein (MT) is induced by various types of oxidative stress. However, whether or not MT is induced in renal ischemia/reperfusion injury, in which oxidative stress is believed to play a major role, remains unknown. The present study investigated MT expression in the kidneys of rats with ischmic acute renal failure (IARF). Rats were subjected to 60 min of bilateral renal ischemia followed by reperfusion. Renal MT mRNA expression was then analyzed by Northern blotting. MT expression in ischemic kidney was also localized by in situ hybridization and immunohistochemistry. Renal MT mRNA expression, which was barely detectable in the sham-operated control kidney, increased significantly at 3 h afer reperfsion, continued to increase to a maximal level at 24 h that was maintained for 48 h. The level of MT mRNA expression returned to that of the control by day 4. A morphological study revealed that MT was expressed exclusively in the renal tubular epithelial cells, which are the targets of ischemia/reperfusion injury, and that MT predominated in the outer medulla in the IARF rat kidney at transcriptional and translational levels. These results suggest that MT induced in the IARF rat kidney plays an important role in protecting renal cells against oxidative stress induced by ischemia/reperfusion.

Topics: Acute Kidney Injury; Animals; Creatinine; In Situ Hybridization; Ischemia; Kidney; Male; Metallothionein; Rats; Rats, Sprague-Dawley; RNA, Messenger

The hepatic response to injury is orchestrated by the expression of different gene groups (i.e., heat shock and acute phase). In the present study, the expression of heat shock and acute phase genes was analyzed in the context of a localized injury, regional hepatic ischemia-reperfusion. Left and median liver lobes were subjected to 1 h of ischemia, whereas blood flow was maintained to the remainder of the organ. After the period of ischemia, the organ was reperfused, and samples of the ischemic and nonischemic liver were obtained at different time points during reperfusion. Expression of the heat shock gene, HSP 72, was detected only in the ischemic liver, whereas expression of the acute phase gene, beta-fibrinogen, and the interleukin-6-inducible gene, metallothionein, was maximally induced in the nonischemic liver and attenuated in the ischemic liver. To determine how the heat shock and acute phase responses were reprioritized during stress, expression of beta-fibronogen and HSP 72 was induced simultaneously in the same animal by administration of endotoxin and total body hyperthermia, respectively. Administration of endotoxin did not impede the expression of HSP 72; however, heat shock attenuated, but did not eliminate, the endotoxin-induced expression of beta-fibronogen. These observations suggest that the heat shock and acute phase responses are not mutually exclusive.

Topics: Acute-Phase Proteins; Acute-Phase Reaction; Animals; Fibrinogen; Gene Expression; Heat-Shock Proteins; Heat-Shock Response; HSP72 Heat-Shock Proteins; Ischemia; Liver; Liver Circulation; Male; Metallothionein; Phosphoenolpyruvate Carboxykinase (GTP); Rats; Rats, Sprague-Dawley; Reperfusion; RNA, Messenger