Acute and Chronic Iron Overloading Differentially Modulates the Expression of Cellular Iron-homeostatic Molecules in Normal Rat Kidney

Abstract

Little is known about the renal responses to acute iron overloading. This study measured the renal tubular expression of transferrin receptor-1 (TfR1), cubilin/megalin receptors, hepcidin, ferroportin, and ferritin chains following subacute intoxication of 40 male Wistar rats with a single oral dose of ferrous iron (300 mg/kg). The animals were randomly subdivided into 4 equal subgroups at the time of necropsy (1, 2, 4, and 8 hr). The results were compared with the controls ( n=15) and with the chronic group ( n=15), which received iron for 4 weeks (75 mg/kg/day; 5 days/week). Although both toxicity models inhibited TfR1, they upregulated the cubilin/megalin receptors and hepcidin, and triggered iron deposition in tubular cells. The ferritin heavy-chain and ferroportin were downregulated in the 2-hr and 4-hr acute subgroups, whereas chronic toxicity promoted their expression, compared with controls. Moreover, the 4-hr and 8-hr subgroups had higher intracellular Fe and marked cell apoptosis compared with the chronic group. In conclusion, the kidney appears to sustain iron reabsorption in both intoxication models. However, the cellular iron storage and exporter proteins were differentially expressed in both models, and their inhibition post-acute toxicity might contribute toward the intracellular accumulation of Fe, oxidative stress, and ferroptosis.

Systemic and local hepcidin as emerging and important peptides in renal homeostasis and pathology

“…). The increased renal hepcidin production with decreased renal ferritin during acute renal iron load observed by Refaat et al seems to be in line with the previous studies . Still, the molecular pathways that induce hepcidin upregulation during hem‐induced injury are to be resolved .…”

“…Hepcidin treatment reduces the levels of 4-HNE (marker of oxidative stress)RT-PCR, western blot, mass spectrometry in mouse model with hemoglobin-induced kidney injury Systemic hepcidin downregulates renal FPN protein levels van Swelm et al[21] Treatment with hepcidin in hemoglobin-induced kidney injury increases renal hepcidin expressionHemoglobin reduces the level of systemic hepcidin absorption in distal tubule, but it induces renal hepcidin expressionSystemic hepcidin is absorbed in proximal tubule via megalin Treatment with hepcidin reduces renal IL-6 and NGAL mRNA RT-PCR, immunofluorescence, ELISA in rat models Acute iron load increases renal hepcidin protein levels Refaat et al[50] …”

Vitamin D3 and calcium cosupplementation alleviates cadmium hepatotoxicity in the rat: Enhanced antioxidative and anti‐inflammatory actions by remodeling cellular calcium pathways

“…Stained sections were observed at ×40 magnification on an EVOS FL microscopy. Apoptotic bodies were identified by the emission of green fluorescence dye and the apoptosis index was calculated by counting the percentage of apoptotic/necrotic cells in 15 random nonoverlapping fields from each tissue section using the cell counter tool provided with the microscope software, as previously described …”

“…Apoptotic bodies were identified by the emission of green fluorescence dye and the apoptosis index was calculated by counting the percentage of apoptotic/necrotic cells in 15 random nonoverlapping fields from each tissue section using the cell counter tool provided with the microscope software, as previously described. [42] 2.9 | Quantitative reverse transcription-polymerase chain reaction Table S1), and 1 µL cDNA (25 ng). The NCs included a minus-reverse transcription (RT) control from the previous RT step and another minus-template PCR, in which nuclease-free water was used as a template.…”

Effects of Endurance Workouts on Thyroid Hormone Metabolism and Biochemical Markers in Athletes

“…Metabolic or cardio metabolic changes occur in the organism due to iron deficiency or excessive accumulation. In addition, iron deficiency creates differences in thyroid hormone metabolism and hematological parameters (Chifman et al, 2014;Corrales-Agudelo et al, 2016;Gallego-Narbón et al, 2019;Pantopoulos et al, 2012;Refaat et al, 2018;Vincent et al, 2019). Iron is one of the important determinants of athletic performance efficiency and endurance parameters in athletes due to its effect on oxidative metabolism (Denis & Conway, 2019;Hinton, 2014;Nandadeva et al, 2019).…”