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A comparison between centrally and systemically administered erythropoietin on kidney protection in a model of fixed-volume hemorrhagic shock in male rats

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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 (SaO2) was measured during experiments. Urine and renal tissue samples were stored for ex-vivo indices assessments.

Results

Erythropoietin (systemically/centrally administered) significantly improved SaO2, 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.

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Data Availability

All data will be available by reasonable request.

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Funding

This research was supported by a grant (no = 27721) from Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mina Ranjbaran, Mehri Kadkhodaee, Leila Hafazeh & Behjat Seifi

  2. Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Maryam Adelipour

  3. Research and clinical center for infertility, Yazd Rreproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Keivan Lorian

Authors
  1. Mina Ranjbaran
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  2. Mehri Kadkhodaee
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  3. Maryam Adelipour
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  4. Leila Hafazeh
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  6. Behjat Seifi
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Correspondence to Behjat Seifi.

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No competing interests declared.

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Experimental protocols and animal care methods in the experiments were approved by the Animal Experimental Committee at Tehran University of Medical Sciences (Project number: 27721-30-04-93, Approval ID: 27721).

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Ranjbaran, M., Kadkhodaee, M., Adelipour, M. et al. A comparison between centrally and systemically administered erythropoietin on kidney protection in a model of fixed-volume hemorrhagic shock in male rats. Mol Biol Rep 50, 4781–4789 (2023). https://doi.org/10.1007/s11033-023-08412-6

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