metallothionein and thiobarbituric-acid

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury.

Topics: Acute Kidney Injury; Animals; Antioxidants; Disease Models, Animal; Glomerular Filtration Rate; Kidney; Lipid Peroxidation; Male; Metallothionein; Rats; Rats, Wistar; Reactive Oxygen Species; Renal Circulation; Reperfusion Injury; Thiobarbiturates; Treatment Outcome; Zinc

Topics: Alcoholic Intoxication; Animals; Lipid Peroxidation; Liver; Malondialdehyde; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Poisoning; Thiobarbiturates

The effect of maternal copper (Cu) deficiency on various proteins was studied to determine if the changes were reversible or persistent with Cu repletion. The functional consequences of these alterations were assessed by exposing the animals to an oxidative stress (endotoxin), and by measuring the formation of benzo[a]pyrene-DNA adducts in vitro. Throughout gestation and lactation, mice were fed a Control diet (10 micrograms Cu/g diet) or a Low Cu diet (1 microgram Cu/g diet). On day 18, the offspring were killed or switched to the Control diet and killed on day 42 following a single injection of saline or endotoxin on day 41. In day-18 offspring, Cu deficiency resulted in decreased hematocrit values, ceruloplasmin activity, liver and tissue Cu levels, and metallothionein concentrations. Cu repletion restored all but metallothionein levels. Early Cu deficiency led to higher brain CuZn superoxide dismutase activity on day 42, and higher levels of brain thiobarbituric acid reactive substances (TBARS) in endotoxin-treated mice. Liver TBARS were lower in day-18 Low Cu offspring and in day-42 Low Cu offspring treated with endotoxin than age-matched Controls. Cytochrome P-450 concentrations were lower in Low Cu, endotoxin-treated males than in Controls. These results show that Cu deficiency-mediated alterations during early development are not immediately reversed with Cu repletion.

Topics: 7-Alkoxycoumarin O-Dealkylase; Animals; Benzo(a)pyrene; Body Weight; Brain; Ceruloplasmin; Copper; Cytochrome P-450 Enzyme System; Embryonic and Fetal Development; Female; Hematocrit; Hemoglobins; Kidney; Liver; Metallothionein; Mice; Mice, Inbred Strains; Organ Size; Pregnancy; Pregnancy Complications; Superoxide Dismutase; Thiobarbiturates; Trace Elements