Cellular mechanisms underlying the increased duodenal iron absorption in rats in response to phenylhydrazine‐induced haemolytic anaemia

Abstract

Haemolytic anaemia induced by phenylhydrazine (PZ) promotes iron absorption across rat small intestine. This present study investigates the role of the brush border potential difference (Vm) and mucosal reducing activity in the response. In addition, quantitative autoradiography was used to assess PZ-induced changes in the villus localization of brush border iron uptake. Iron transfer from duodenum to blood was increased significantly 5 days after treatment with PZ. Autoradiography showed that most brush border iron uptake occurred at the upper villus region and the maximal rate was increased fourfold by PZ. Duodenal villus length was increased in PZ-treated rats. PZ treatment did not influence mucosal reducing activity but Vm, measured using duodenal sheets, increased from -50 to -57 mV (P < 0.001) and this was due to a reduced brush border sodium permeability. Thus, an expanded absorptive surface and an enhanced electrical driving force for iron uptake across the duodenal brush border are important adaptations for increased iron absorption in PZ-induced haemolytic anaemia.

EPO-dependent induction of erythroferrone drives hepcidin suppression and systematic iron absorption under phenylhydrazine-induced hemolytic anemia

“…Hepcidin expression has been shown to be suppressed on day 3 after PHZ administration in order to promote iron absorption [19,20]. In present study, we found that the hepcidin mRNA levels were gradually reduced in over the time course, almost up to 8-fold on day 5, a then was ameliorated compared to the untreated control ( Fig.…”

“…1C, P b 0.05). By contrast, consistent with reduced RBC content, the percentage of R6 cells was also significantly decreased in PHZ-treated group at 40 mg/kg and 80 mg/kg, compared with the control group (4.41% and 3.2% vs. 5.57%) ( Previous studies have suggested that PHZ-induced hemolytic anemia could promote iron absorption in duodenum of experimental animals [19,20]. In the current study, we found that serum heme and non-heme iron levels were significantly increased in mice with PHZ administration at 40 mg/kg (2-fold and 3-fold) and 80 mg/kg (2.5-fold and 7-fold) compared to control (Fig.…”

“…It is well documented that PHZ-induced anemia is a classic model for the study of the pathogenesis of hemolytic anemia and the molecular mechanisms of anemia related to other physiological processes or diseases [19][20][21]26]. Here, PHZ-induced hemolysis model was used to analyze the relationship between stress erythropoiesis and iron metabolism.…”

“…Previous studies indicated hepcidin expression was repressed in phenylhydrazine (PHZ)-induced hemolytic anemia [18][19][20][21][22]. Nonetheless, the mechanisms for the pathogenic role of erythroid regulator in hepcidin suppression upon PHZ-induced hemolysis are elusive, and specifically, no insight has been gained into physiological hepcidin suppression of hemolytic anemia in a long term course.…”

Toxicological overview of a novel strobilurin fungicide, orysastrobin

“…Studies in which rats were treated with an iron-deficient diet have shown that this treatment results in similar duodenal changes. [1][2][3] A mechanistic study in mice also established increased proliferation of the epithelium of duodenal mucosa after 4 weeks at the carcinogenic dose of 2000 ppm, demonstrating that the same mechanism occurs in this species.…”