Related Experiment Video
Updated: Sep 26, 2026
Mouse Model of Acute to Chronic Kidney Disease Transition Induced by Renal Ischemia/Reperfusion Injury
Published on: February 10, 2026
Characterization of myoglobin toxicity in renal cortical slices from Fischer 344 rats
Jennifer L Minigh1, Monica A Valentovic
1Department of Pharmacology, Joan C Edward School of Medicine, Marshall University, 1542 Spring Valley Drive, Huntington, WV 24704-9388, USA.
Abstract:
Rhabdomyolysis is associated with acute renal failure. The following study first characterized myoglobin in vitro toxicity using renal cortical slices isolated from male Fischer 344 rats. This model provided interaction between various cells within the nephron and provides myoglobin access predominantly through the basolateral membrane. Second, this study examined the effect of deferoxamine (DFX) and glutathione on myoglobin toxicity to determine the role of radicals and iron. Renal cortical slices were incubated for 30-120 min with 0, 4, 10 or 12 mg/ml myoglobin. Myoglobin was pretreated with 4 mM ascorbic acid prior to addition to the slices to ensure that myoglobin was in its reduced state. In other experiments tissues were pretreated for 15 min with 0.1 mM of the iron chelator DFX or 30 min with 1 mM glutathione prior to co-incubation with myoglobin. Finally, slices were pretreated with 1 mM glutathione for 30 min, rinsed and incubated only with myoglobin. Early event changes occurred within a 60 min exposure and included a decline in pyruvate-stimulated gluconeogenesis, increased lipid peroxidation levels and decreased glutathione levels. Loss of ATP levels and increased lactate dehydrogenase (LDH) release required a 120 min exposure to myoglobin. DFX reduced myoglobin induced effects on LDH leakage but had no effect on gluconeogenesis suggesting that myoglobin toxicity had an iron dependent (LDH) and independent (gluconeogenesis) pathway. Pretreatment with glutathione provided complete protection and was mediated by intracellular events.
Insights
Myoglobin causes kidney damage through iron-dependent and independent pathways. Glutathione protects kidney cells from myoglobin toxicity, while deferoxamine partially mitigates damage.
Area of Science:
- Nephrology
- Toxicology
- Biochemistry
Background:
- Rhabdomyolysis, a condition involving muscle breakdown, is a known cause of acute kidney injury.
- Myoglobin, released during rhabdomyolysis, is implicated in renal damage.
- Understanding myoglobin's toxic mechanisms is crucial for developing protective strategies.
Purpose of the Study:
- To characterize the in vitro toxicity of myoglobin on rat renal cortical slices.
- To investigate the protective effects of deferoxamine (DFX) and glutathione against myoglobin-induced renal cell injury.
- To elucidate the roles of iron and radicals in myoglobin nephrotoxicity.
Main Methods:
- Isolated male Fischer 344 rat renal cortical slices were incubated with varying concentrations of myoglobin.
- Myoglobin was pre-treated with ascorbic acid to ensure a reduced state.
- Tissues were pre-treated with deferoxamine (iron chelator) or glutathione before myoglobin exposure.
Main Results:
- Myoglobin exposure led to decreased gluconeogenesis, increased lipid peroxidation, and reduced glutathione levels within 60 minutes.
- ATP depletion and lactate dehydrogenase (LDH) release occurred after 120 minutes of myoglobin exposure.
- Deferoxamine reduced LDH release (iron-dependent) but not gluconeogenesis impairment (iron-independent). Glutathione provided complete protection.
Conclusions:
- Myoglobin induces renal toxicity through both iron-dependent and iron-independent mechanisms.
- Glutathione effectively protects renal cells from myoglobin toxicity via intracellular pathways.
- These findings highlight potential therapeutic targets for preventing rhabdomyolysis-induced acute kidney injury.
