A Comparison Between Centrally and Systemically Administered Erythropoietin on Kidney Protection in a Model of Fixed-volume Hemorrhagic Shock in Male Rats

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2023 Apr 6

PMID 37024748

Authors

Mina Ranjbaran

Mehri Kadkhodaee

Maryam Adelipour

Leila Hafazeh

Keivan Lorian

Behjat Seifi

Affiliations

Soon will be listed here.

Abstract

Background: In this study, a comparison between centrally and systemically administered erythropoietin (EPO) was performed on nephroprotection during hemorrhagic shock (HS) in male rats.

Methods: Male rats were allocated into four experimental groups. (1) Sham; a guide cannula was inserted into the left lateral ventricle and other cannulas were placed into the left femoral artery and vein. (2) HS; stereotaxic surgery was done to insert a cannula in the left lateral ventricle and after a 7-day recovery; hemorrhagic shock and resuscitation were performed. (3) EPO-systemic; the procedure was the same as the HS group except that animals received 300 IU/kg erythropoietin into the femoral vein immediately before resuscitation. (4) EPO-central; animals was treated with erythropoietin (2 IU/rat) into the left lateral ventricle before resuscitation. Arterial oxygen saturation (SaO) was measured during experiments. Urine and renal tissue samples were stored for ex-vivo indices assessments.

Results: Erythropoietin (systemically/centrally administered) significantly improved SaO renal functional and oxidative stress parameters and decreased renal inflammatory (TNF-α and IL-6) mRNA expression compared to the HS group. EPO-treated groups showed a decrease in active form of caspase-3 protein level and an increase in autophagy activity in comparison with the HS group.

Conclusion: Considering the fact that the effective dose of systemic EPO (300 IU/kg) was roughly 50 times higher than that of central administration (2 IU/rat), centrally administered EPO was accompanied by more advantageous consequences than systemic way. EPO is likely to act as a neuro-modulator or neuro-mediator in the central protection of organs including the kidneys.

References

Kholmukhamedov A, Czerny C, Hu J, Schwartz J, Zhong Z, Lemasters J . Minocycline and doxycycline, but not tetracycline, mitigate liver and kidney injury after hemorrhagic shock/resuscitation. Shock. 2014; 42(3):256-63. PMC: 4134396. DOI: 10.1097/SHK.0000000000000213. View

Ranjbaran M, Kadkhodaee M, Seifi B, Adelipour M, Azarian B . Erythropoietin attenuates experimental haemorrhagic shock-induced renal damage through an iNOS- dependent mechanism in male Wistar rats. Injury. 2017; 48(2):262-269. DOI: 10.1016/j.injury.2017.01.010. View

Wang Y, Yan J, Xi L, Qian Z, Wang Z, Yang L . Protective effect of crocetin on hemorrhagic shock-induced acute renal failure in rats. Shock. 2012; 38(1):63-7. DOI: 10.1097/SHK.0b013e3182596ec4. View

Gilbert K, Rousseau G, Bouchard C, Dunberry-Poissant S, Baril F, Cardinal A . Caspase-(8/3) activation and organ inflammation in a rat model of resuscitated hemorrhagic shock: A role for uric acid. J Trauma Acute Care Surg. 2018; 86(3):431-439. DOI: 10.1097/TA.0000000000002152. View

Wang L, Di L, Noguchi C . Erythropoietin, a novel versatile player regulating energy metabolism beyond the erythroid system. Int J Biol Sci. 2014; 10(8):921-39. PMC: 4147225. DOI: 10.7150/ijbs.9518. View

Digicaylioglu M, Bichet S, Marti H, Wenger R, Rivas L, Bauer C . Localization of specific erythropoietin binding sites in defined areas of the mouse brain. Proc Natl Acad Sci U S A. 1995; 92(9):3717-20. PMC: 42032. DOI: 10.1073/pnas.92.9.3717. View

Marti H, Wenger R, Rivas L, Straumann U, Digicaylioglu M, Henn V . Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci. 1996; 8(4):666-76. DOI: 10.1111/j.1460-9568.1996.tb01252.x. View

Ranjbaran M, Kadkhodaee M, Seifi B . Renal tissue pro-inflammatory gene expression is reduced by erythropoietin in rats subjected to hemorrhagic shock. J Nephropathol. 2017; 6(2):69-73. PMC: 5418073. DOI: 10.15171/jnp.2017.12. View

Yoo S, Cho B, Lee D, Son G, Lee Y, Han H . The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage. Cell Death Dis. 2017; 8(8):e3003. PMC: 5596568. DOI: 10.1038/cddis.2017.381. View

10.

Hasselblatt M, Ehrenreich H, Siren A . The brain erythropoietin system and its potential for therapeutic exploitation in brain disease. J Neurosurg Anesthesiol. 2006; 18(2):132-8. DOI: 10.1097/00008506-200604000-00007. View

11.

Gu L, Xu H, Wang F, Xu G, Sinha D, Wang J . Erythropoietin exerts a neuroprotective function against glutamate neurotoxicity in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2014; 55(12):8208-22. DOI: 10.1167/iovs.14-14435. View

12.

Seifi B, Kadkhodaee M, Ranjbaran M, Bakhshi E . Nephroprotection through the Akt/eNOS pathway by centrally administered erythropoietin in a rat model of fixed-volume hemorrhage. Life Sci. 2017; 193:180-185. DOI: 10.1016/j.lfs.2017.11.003. View

13.

Maiese K . Erythropoietin and diabetes mellitus. World J Diabetes. 2015; 6(14):1259-73. PMC: 4620106. DOI: 10.4239/wjd.v6.i14.1259. View

14.

Zhong L, Zhang H, Ding Z, Li J, Lv J, Pan Z . Erythropoietin-Induced Autophagy Protects Against Spinal Cord Injury and Improves Neurological Function via the Extracellular-Regulated Protein Kinase Signaling Pathway. Mol Neurobiol. 2020; 57(10):3993-4006. DOI: 10.1007/s12035-020-01997-0. View

15.

Bendix I, Schulze C, Von Haefen C, Gellhaus A, Endesfelder S, Heumann R . Erythropoietin modulates autophagy signaling in the developing rat brain in an in vivo model of oxygen-toxicity. Int J Mol Sci. 2012; 13(10):12939-51. PMC: 3497305. DOI: 10.3390/ijms131012939. View

16.

Ahmadi-Yazdi C, Williams B, Oakes S, Moore Jr F . Attenuation of the effects of rat hemorrhagic shock with a reperfusion injury-inhibiting agent specific to mice. Shock. 2008; 32(3):295-301. PMC: 2993186. DOI: 10.1097/SHK.0b013e3181995e0c. View

17.

Seifi B, Kadkhodaee M, Bakhshi E, Ranjbaran M, Ahghari P, Rastegar T . Enhancement of renal oxidative stress by injection of angiotensin II into the paraventricular nucleus in renal ischemia-reperfusion injury. Can J Physiol Pharmacol. 2014; 92(9):752-7. DOI: 10.1139/cjpp-2014-0108. View

18.

Ali R, Al-Obaidi F, Arif H . The Role of Urinary N-acetyl Beta-D-glucosaminidase in Children with Urological Problems. Oman Med J. 2014; 29(4):285-8. PMC: 4138411. DOI: 10.5001/omj.2014.74. View

19.

AEBI H . Catalase in vitro. Methods Enzymol. 1984; 105:121-6. DOI: 10.1016/s0076-6879(84)05016-3. View

20.

Griffith O . Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem. 1980; 106(1):207-12. DOI: 10.1016/0003-2697(80)90139-6. View