Effects of partial hepatectomy on extrarenal erythropoietin production in rats

Abstract

Studies were performed to determine the effects of partial hepatectomy on extra-renal erythropoietin production. Rats were either partially hepatectomized or sham operated. At intervals of from 5 min to 7 days afterward, both kidneys were removed from cohorts of the above two groups of rats and the animals were then exposed to hypoxia for 7.5 hr. Immediately afterward, their plasma was collected and its erythropoietin titer was assayed. Rats which were partially hepatectomized 2–4 days prior to nephrectomy and hypoxia had significantly higher plasma erythropoietin levels than did sham- operated controls, whereas rats hepatectomized 5 min, 1 day, or 7 days prior to nephrectomy and hypoxia did not. These data are consistent with the conclusion that extrarenal erythropoietin production is enhanced in association with rapid regeneration of hepatic cells.

Upstream Pathways Regulating Erythropoietin Gene Expression in the Liver During Acute Phase Response: A Central Role for Il-6.

“…Indeed, he showed two experimental conditions resulting in profound increments in the plasma erythropoietin levels of hypoxic anephric rats: interventions that cause liver damage and the administration of rennin or angiotensin. The observations reported in the mentioned study were also repeated by other groups who proved that liver injury by partial hepatectomy, CCl4 administration and bile duct ligation in rats were able to induce an increase of the plasmatic Epo concentration (38), and during the present investigation the same results were confirmed with an analysis of Epo mRNA expression in the same experimental conditions. The cellular source of Epo production still remains an important goal to achieve, and the heterogenous cell population of the liver gave rise to several controversial debates still not solved (39).…”

Hypoxia-inducible factors not only regulate but also are myeloid-cell treatment targets

“…The investigators observed that bilateral nephrectomy abrogated the erythropoietic effect of CoCl 2 in rats and rabbits 14 . Later, the liver was identified as an additional extrarenal EPO source 15–22 . Most clinical observations supported the importance of the kidneys for erythropoiesis with complete erythroblastopenia in anuric renal failure patients 23 and after nephrectomy, 24 and polycythemia in patients with renal pathologies, such as renal cysts, hypernephroma, or hydronephrosis 25–33 .…”

“…14 Later, the liver was identified as an additional extrarenal EPO source. [15][16][17][18][19][20][21][22] Most clinical observations supported the importance of the kidneys for erythropoiesis with complete erythroblastopenia in anuric renal failure patients 23 and after nephrectomy, 24 and polycythemia in patients with renal pathologies, such as renal cysts, hypernephroma, or hydronephrosis. [25][26][27][28][29][30][31][32][33] In the 1970s, EPO was isolated from the urine of anemic patients [34][35][36] followed by cloning and recombinant expression a decade later.…”