Resistance of rat kidney mitochondrial membranes to oxidation induced by acute iron overload

Galleano, Mónica; Farré, Stella M.; Turrens, Julio F.; Puntarulo, Susana

doi:10.1016/0300-483x(94)90116-3

Cited by 8 publications

(4 citation statements)

References 28 publications

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“…11 In another study, vitamin E was effective in controlling iron-dextran-dependent OFR generation in kidneys. 12 Serum vitamin E concentrations were lower in thalassemic patients with diabetes, compared with diabetic patients without iron overload. 13 In the present study, vitamin E levels were markedly reduced in the Fe group compared to controls.…”

Section: Discussionmentioning

confidence: 98%

The role of nitric oxide in iron-induced rat renal injury

Kadkhodaee

Gol

2004

Hum Exp Toxicol

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Iron overload and enhanced hydroxyl radical (•OH) formation have been implicated as the causative factors of oxidative stress in different organs. Both pro-oxidant and anti-oxidant properties have been reported for nitric oxide (NO) in iron-mediated tissue injury. To determine the contribution of NO to iron-induced renal injury, eight groups of rats (eight in each group) were studied as follows: control (normal saline), L-Arg (L-arginine as a substrate of NO synthase, 400 mg/kg), L-NAME (an inhibitor of NO synthase, 8 mg/kg), Fe (iron dextran, 600 mg/kg), DFO (deferroxamine as a chelator of iron, 150 mg/kg), Fe+L-Arg, Fe+L-NAME, DFO+L-Arg. Twenty-four hours after the injections, blood samples were taken and kidneys removed for biochemical analysis. Plasma creatinine and urea were used to stimulate renal function. Renal tissue and plasma vitamin E levels, the most important endogenous fat soluble antioxidant, were measured by HPLC and UV detection. In this study, renal function was markedly reduced in the Fe group compared to controls (creatinine, 1.02± 0.05 mg/dL versus 0.78±0.04 P <0.05; urea, 49.59±1.69 mg/dL versus 40.75±0.86, P <0.01). Vitamin E levels were significantly lower in the Fe group compared to controls (plasma P <0.01; renal tissue P <0.05). Administration of L-Arg to Fe-treated groups prevented these reductions. L-NAME increased iron-induced toxicity significantly, demonstrated by further reduction in the vitamin E levels and renal function compared to the Fe group alone. We concluded that NO plays an important role in protecting the kidney from iron-induced nephrotoxicity. NO synthase blockade enhances iron-mediated renal toxicity in this model.

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Section: Discussionmentioning

confidence: 98%

The role of nitric oxide in iron-induced rat renal injury

Kadkhodaee

Gol

2004

Hum Exp Toxicol

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“…Many studies have shown that iron over load in experimental animals can produce ox idative damage to biological membranes in vivo by catalyzing hydrogen peroxide (H2O2) to the hydroxyl radical ('OH) [9][10][11][12][13][14][15] which can initiate a chain reaction in lipid peroxida tion and result in membrane injury. Lipid peroxidation is a complex process known to occur in both plants and animals.…”

Section: Introductionmentioning

confidence: 99%

Differential Behaviour of Cell Membranes towards Iron-Induced Oxidative Damage and the Effects of Melatonin

Tang

Xu²,

Qian³

1997

Neurosignals

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The ability of melatonin to protect iron-induced lipid peroxidation was studied in various rat cell membranes. The concentration of cellular membrane malondialdehyde (MDA) was used as an index of induced oxidative membrane damage. Cell membranes from the brain, heart, kidney and liver of the male Sprague-Dawley rat were incubated with ferric ammonium citrate (20 µg/ml iron) alone for 3 h and concomitant with varying concentrations of melatonin ranging from 125 to 2,000 µM. The basal MDA levels of all the cell membranes were 25.0 ± 1.4 (brain), 21.2 ±.2 (heart), 10.0 ± 0.9 (kidney) and 20.7 ± 0.4 (liver) µM/g membrane protein, and the highest lipid peroxidation after exposure to iron occurred in the kidney (314.4%), followed by the heart (151.3%), the liver (130.4%) and the brain (121.7%). This peroxidative effect was completely (ED₅₀ 846.7 µM for the heart) and partially suppressed by melatonin (ED₅₀ 462.1 µM for the brain, 178.3 µM for the kidney and 886.6 µM for the liver). This inhibition effect on MDA production by these cell membranes was also found – except for the liver – if melatonin was used alone. These results show that the direct effect of lipid peroxidation on cellular membrane following iron exposure is markedly reduced by melatonin.

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“…Several models of AKI by acute Fe overload of the kidney show consistently damaged kidney mitochondria induced by increased mitochondrial Fe and oxidative stress. Twenty hours after a single intraperitoneal injection of iron-dextran (500 mg/kg body weight) into rats, increased mitochondrial Fe correlated with increased lipid peroxidation and decreased mitochondrial α-tocopherol content in cortex and medulla ( Galleano et al, 1994 ), whereas other mitochondrial functions were unaffected. Thirty minutes to 3 h after intraperitoneal injection of Fe- nitrilotriacetic acid (10 or 20 mg Fe/kg body weight), mitochondria of rat kidney PT cells showed increased oxidative damage, supported by accumulation of 4-hydroxy-2-nonenal-modified proteins, indicating oxidative breakdown of polyunsaturated fatty acids and related esters ( Zainal et al, 1999 ).…”

Section: Fe and Mitochondrial Damagementioning

confidence: 99%

Iron and Cadmium Entry Into Renal Mitochondria: Physiological and Toxicological Implications

Thévenod

Lee

Garrick

2020

Front. Cell Dev. Biol.

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Regulation of body fluid homeostasis is a major renal function, occurring largely through epithelial solute transport in various nephron segments driven by Na + /K + -ATPase activity. Energy demands are greatest in the proximal tubule and thick ascending limb where mitochondrial ATP production occurs through oxidative phosphorylation. Mitochondria contain 20–80% of the cell’s iron, copper, and manganese that are imported for their redox properties, primarily for electron transport. Redox reactions, however, also lead to reactive, toxic compounds, hence careful control of redox-active metal import into mitochondria is necessary. Current dogma claims the outer mitochondrial membrane (OMM) is freely permeable to metal ions, while the inner mitochondrial membrane (IMM) is selectively permeable. Yet we recently showed iron and manganese import at the OMM involves divalent metal transporter 1 (DMT1), an H + -coupled metal ion transporter. Thus, iron import is not only regulated by IMM mitoferrins, but also depends on the OMM to intermembrane space H + gradient. We discuss how these mitochondrial transport processes contribute to renal injury in systemic (e.g., hemochromatosis) and local (e.g., hemoglobinuria) iron overload. Furthermore, the environmental toxicant cadmium selectively damages kidney mitochondria by “ionic mimicry” utilizing iron and calcium transporters, such as OMM DMT1 or IMM calcium uniporter, and by disrupting the electron transport chain. Consequently, unraveling mitochondrial metal ion transport may help develop new strategies to prevent kidney injury induced by metals.

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Resistance of rat kidney mitochondrial membranes to oxidation induced by acute iron overload

Cited by 8 publications

References 28 publications

The role of nitric oxide in iron-induced rat renal injury

The role of nitric oxide in iron-induced rat renal injury

Differential Behaviour of Cell Membranes towards Iron-Induced Oxidative Damage and the Effects of Melatonin

Iron and Cadmium Entry Into Renal Mitochondria: Physiological and Toxicological Implications

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