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Drug Res (Stuttg) 2023; 73(05): 289-295
DOI: 10.1055/a-2015-7976
Original Article

Prazosin Protects the Liver Against Renal Ischemia/Reperfusion Injury in Rats

Fatemeh Khajepour   *
1   Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
,
Fariba Mahmoodpoor   *
2   Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Department of Persian Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
,
Elmira Jafari
1   Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
,
Farzad Kakaei
4   Department of General and Vascular Surgery, Tabriz University of Medical Sciences, Tabriz, Iran
,
Farina Bahraminia
1   Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
,
Shadi Aghajani
1   Faculty of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran
,
Sepideh Zununi Vahed
2   Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
,
Yasin Bagheri
2   Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
› Institutsangaben Funding This study was supported and funded by Kidney Research Center of Tabriz University of Medical Sciences (Grant number, #65590).
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Abstract

Acute kidney injury (AKI) is a common subsequent problem after many medical conditions. AKI is associated with distant organ dysfunction where systemic inflammation and oxidative stress play major roles. In this study, the effect of Prazosin, an α1-Adrenergic receptor antagonist, was investigated on the liver injury induced by kidney ischemia-reperfusion (I/R) in rats. Male adult Wistar rats (n=21) were divided into three groups: sham, kidney I/R, and kidney I/R pre-treated with Prazosin (1 mg/kg). Kidney I/R was induced by vascular clamping of the left kidney for 45 min to reduce the blood flow. Oxidative and antioxidant factors along with apoptotic (Bax, Bcl-2, caspase3), and inflammatory (NF-κβ, IL-1β, and IL-6) factors were measured in the liver at protein levels. Prazosin could reserve liver function (p<0.01) and increase glutathione level (p<0.05) after kidney I/R significantly. Malonil dialdehyde (MDA), a lipid peroxidation marker, was diminished more significantly in Prazosin-treated rats compared to the kidney I/R group (p<0.001). Inflammatory and apoptotic factors were diminished by Prazosin pre-treatment in the liver tissue (p<0.05). Pre-administration of Prazosin could preserve liver function and decrease its inflammatory and apoptotic factors under kidney I/R conditions.

Key words

acute kidney injury - prazosin - liver injury - distant organs

* These authors contributed equally to this work and should be considered as co-first authors.




Publikationsverlauf

Eingereicht: 24. November 2022

Angenommen: 17. Januar 2023

Artikel online veröffentlicht:
20. März 2023

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  • References

  • 1 Yarijani ZM. et al. Crocin has anti-inflammatory and protective effects in ischemia-reperfusion induced renal injuries. Iranian journal of basic medical sciences 2017; 20 p 753
    PubMedGoogle Scholar
  • 2 Susantitaphong P. et al. World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol 2013; 8 p 1482-1493
    CrossrefPubMedGoogle Scholar
  • 3 Lane K. et al. Renohepatic crosstalk: does acute kidney injury cause liver dysfunction?. Nephrology dialysis transplantation 2013; 28 p 1634-1647
    CrossrefPubMedGoogle Scholar
  • 4 Khastar H. et al. Liver oxidative stress after renal ischemia-reperfusion injury is leukocyte dependent in inbred mice. Iranian journal of basic medical sciences 2011; 14 p 534
    PubMedGoogle Scholar
  • 5 Golab F. et al. Ischemic and non-ischemic acute kidney injury cause hepatic damage. Kidney international 2009; 75 p 783-792
    PubMedGoogle Scholar
  • 6 Shang Y. et al. Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury. Oxid Med Cell Longev 2016; 2016 p 9707292
    CrossrefPubMedGoogle Scholar
  • 7 Golab F. et al. Ischemic and non-ischemic acute kidney injury cause hepatic damage. Kidney Int 2009; 75 p 783-792
    CrossrefPubMedGoogle Scholar
  • 8 Feltes CM. et al. Distant-organ changes after acute kidney injury. Nephron Physiol 2008; 109 p p80-p84
    CrossrefPubMedGoogle Scholar
  • 9 Husain-Syed F, Rosner MH, Ronco C. Distant organ dysfunction in acute kidney injury. Acta Physiologica 2020; 228 p e13357
    CrossrefPubMedGoogle Scholar
  • 10 Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 2009; 1 p a001651
    CrossrefPubMedGoogle Scholar
  • 11 Bagheri Y. et al. Protective effects of Gamma Oryzanol on distant organs after kidney ischemia-reperfusion in rats: A focus on liver protection. Human & Experimental Toxicology 2020; p 0960327120979014
    PubMedGoogle Scholar
  • 12 Bagheri Y. et al. Hepatoprotective effects of sericin on aging-induced liver damage in mice. Naunyn Schmiedebergs Arch Pharmacol 2021; 394 p 2441-2450
    CrossrefPubMedGoogle Scholar
  • 13 Kirwan CJ. et al. Acute kidney injury reduces the hepatic metabolism of midazolam in critically ill patients. Intensive Care Med 2012; 38 p 76-84
    CrossrefPubMedGoogle Scholar
  • 14 Park SW. et al. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy. Lab Invest 2011; 91 p 63-84
    CrossrefPubMedGoogle Scholar
  • 15 Doi K, Rabb H. Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. Kidney Int 2016; 89 p 555-564
    CrossrefPubMedGoogle Scholar
  • 16 Randle L. et al. α1–Adrenoceptor antagonists prevent paracetamol-induced hepatotoxicity in mice. British journal of pharmacology 2008; 153 p 820-830
    CrossrefPubMedGoogle Scholar
  • 17 Zubairi MB, Ahmed JH, Al-Haroon SS. Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits. Indian journal of pharmacology 2014; 46 p 644-648
    PubMedGoogle Scholar
  • 18 Brazvan B. et al. Key Immune Cell Cytokines Affects the Telomere Activity of Cord Blood Cells In vitro. Adv Pharm Bull 2016; 6 p 153-161
    CrossrefPubMedGoogle Scholar
  • 19 Sanusi KO. et al. Co-administration of prazosin and propranolol with glibenclamide improves anti-oxidant defense system in endothelial tissue of streptozotocin-induced diabetic Wistar rats. Journal of Basic and Clinical Physiology and Pharmacology 2020; 32
    PubMedGoogle Scholar
  • 20 Rahimi M. et al. Renoprotective effects of prazosin on ischemia-reperfusion injury in rats. Human & Experimental Toxicology 2021; 40 p 11
    CrossrefPubMedGoogle Scholar
  • 21 Verplaetse TL. et al. Effects of prazosin, an α1-adrenergic receptor antagonist, on the seeking and intake of alcohol and sucrose in alcohol-preferring (P) rats. Alcohol Clin Exp Res 2012; 36 p 881-886
    CrossrefPubMedGoogle Scholar
  • 22 Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int 2012; 81 p 942-948
    CrossrefPubMedGoogle Scholar
  • 23 Hassoun HT. et al. Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy. Am J Physiol Renal Physiol 2007; 293 p F30-F40
    CrossrefPubMedGoogle Scholar
  • 24 Kianian F. et al. Protective effects of celecoxib on ischemia reperfusion – induced acute kidney injury: comparing between male and female rats. Iranian journal of basic medical sciences 2019; 22 p 43
    PubMedGoogle Scholar
  • 25 Bagheri Y. et al. Comparative study of gavage and intraperitoneal administration of gamma-oryzanol in alleviation/attenuation in a rat animal model of renal ischemia/reperfusion-induced injury. Iranian Journal of Basic Medical Sciences 2021; 24 p 175-183
    PubMedGoogle Scholar
  • 26 Malekinejad Z. et al. Prazosin Treatment Protects Brain and Heart by Diminishing Oxidative Stress and Apoptotic Pathways After Renal Ischemia Reperfusion. Drug Res (Stuttg) 2022; 72 p 336-342
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 27 Song Q-Q. et al. Genetic variation in the glucocorticoid pathway involved in interindividual differences in the glucocorticoid treatment. Pharmacogenomics 2017; 18 p 293-316
    CrossrefPubMedGoogle Scholar
  • 28 Mori Y. et al. Safety and availability of doxazosin in treating hypertensive patients with chronic renal failure. Hypertension Research 2001; 24 p 359-363
    CrossrefPubMedGoogle Scholar
  • 29 Clement YN, Williams AF. Protection against paracetamol-induced hepatic injury by prazosin pre-treatment in CD-1 mice. Mutat Res 2005; 579 p 182-188
    CrossrefPubMedGoogle Scholar
  • 30 Sulaiman S. et al. Hepatoprotective Effect Of Prazosin Is Comparable To N-Acetylcysteine In Acetaminophen Induced Hepatotoxicity In Mice. J Ayub Med Coll Abbottabad 2020; 32 p 28-32
    PubMedGoogle Scholar
  • 31 Zubairi MB, Ahmed JH, Al-Haroon SS. Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits. Indian J Pharmacol 2014; 46 p 644-648
    CrossrefPubMedGoogle Scholar
  • 32 Sanz AB. et al. NF-κB in renal inflammation. Journal of the American Society of Nephrology 2010; 21 p 1254-1262
    CrossrefPubMedGoogle Scholar