Naringin, Trimetazidine and Baroreflex in Renal Ischemia-Reperfusion Injury

Luis Cuadrado Martin About the author

Keywords:
Flavanones; Flavonoids; Trimetazidine; Vasodilatador Agents; Hypertension; Heart Failure; Renal Reperfusion; Oxidative Stress

The paper “Naringin and trimetazidine improve baroreflex sensitivity and electrical activity of solitary tract nucleus in renal ischemia-reperfusion injury,” published in this journal,11. Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Naringin and Trimetazidine Improve Baroreflex Sensitivity and Nucleus Tractus Solitarius Electrical Activity in Renal Ischemia-Reperfusion Injury. Arq Bras Cardiol. 2021; 117(2):290-297. doi: https://doi.org/10.36660/abc.20200121
https://doi.org/10.36660/abc.20200121...
found improvement in baroreflex sensitivity in an acute ischemia/reperfusion kidney injury model in rats treated by naringin and/or trimetazidine.

Trimetazidine and naringin are substances capable of reducing oxidative stress, documented in many situations. Trimetazidine is a drug with anti-ischemic properties, which acts directly on mitochondria and is able to decrease oxidative stress. Naringin is a polyphenol with antioxidant properties present in several citrus fruits.

Oxidative stress is involved in multiple pathophysiological processes.22. Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012;81(10):942-8. On the other hand, disorder of the baroceptor reflex is involved in the pathogenesis of hypertension33. Valenti VE, Ferreira C, Meneghini A, Ferreira M, Murad N, Ferreira Filho C, et al. Evaluation of baroreflex function in Young spontaneously hypertensive rats. Arq Bras Cardiol. 2009;92(3):205-15.,44. Sousa LE, Favero IFD, Bezerra FS, Souza ABF, Alzamora AC. Environmental Enrichment Promotes Antioxidant Effect in the Ventrolateral Medulla and Kidney of Renovascular Hypertensive Rats. Arq Bras Cardiol. 2019;113(5):905-12. and heart failure.55. Guimarães GV, Belli JF, Bacal F, Bocchi EA. Behavior of central and peripheral chemoreflexes in heart failure. Arq Bras Cardiol. 2011;96(2):161-7. Moreover, this disorder plays a role in chronic kidney disease66. Quarti-Trevano F, Seravalle G, Dell’Oro R, Mancia G, Grassi G. Autonomic Cardiovascular Alterations in Chronic Kidney Disease: Effects of Dialysis, Kidney Transplantation, and Renal Denervation. Curr Hypertens Rep. 2021;23(2):10. and in acute kidney injury.77. Abdulla MH, Johns EJ. The innervation of the kidney in renal injury and inflammation: a cause and consequence of deranged cardiovascular control. Acta Physiol (Oxf). 2017;220(4):404-16. The solitary tract nucleus plays a fundamental role in the baroceptor reflex integration and its action is influenced by oxidative stress.77. Abdulla MH, Johns EJ. The innervation of the kidney in renal injury and inflammation: a cause and consequence of deranged cardiovascular control. Acta Physiol (Oxf). 2017;220(4):404-16.

Attenuation of the baroreflex in acute kidney injury can make it difficult to respond to hemodynamic instability during an episode of acute kidney injury.88. Chen WW, Xiong XQ, Chen Q, Li YH, Kang YM, Zhu GQ. Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension. Acta Physiol (Oxf). 2015;213(4):778-94.,99. Verney C, Legouis D, Voiriot G, Fartoukh M, Labbé V. Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury. J Clin Med. 2021;10(6):1317. Acute kidney injury also shows an increase in oxidative stress.22. Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012;81(10):942-8. Free radicals and reactive oxygen species are produced in abundance in kidney damage due to ischemia/reperfusion and flood the circulatory system causing undesirable effects on various organs, including the solitary tract, which, as we have seen, is an important integrator of the baroreflex activity.

In other models, except acute kidney injury, oxidative stress is correlated with dysfunction of the baroceptors and antioxidants improved their function. Nevertheless, in acute kidney injury, whether this increase in oxidative stress has a cause-and-effect relationship with baroreflex attenuation is controversial. Thus, if, in models of acute kidney injury, by blocking oxidative stress, we could restore the baroreflex, it would be evident that oxidative stress plays this postulated role.

The variation in heart rate to mean arterial pressure ratio compared to the challenge with phenylephrine was the baroreflex index performed in the study of Amini et al.11. Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Naringin and Trimetazidine Improve Baroreflex Sensitivity and Nucleus Tractus Solitarius Electrical Activity in Renal Ischemia-Reperfusion Injury. Arq Bras Cardiol. 2021; 117(2):290-297. doi: https://doi.org/10.36660/abc.20200121
https://doi.org/10.36660/abc.20200121...
Using a stereotactic technique, before inducing acute kidney injury, an electrode was implanted in the solitary tract nucleus of the rats with nucleus activity.11. Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Naringin and Trimetazidine Improve Baroreflex Sensitivity and Nucleus Tractus Solitarius Electrical Activity in Renal Ischemia-Reperfusion Injury. Arq Bras Cardiol. 2021; 117(2):290-297. doi: https://doi.org/10.36660/abc.20200121
https://doi.org/10.36660/abc.20200121...
Thus, in addition to improvement of the baroreflex, there was a reversal of solitary tract nucleus activity attenuation that had been documented concurrently with the reperfusion injury.

These results have pathophysiological implications, insofar as they demonstrate the participation of oxidative stress in the dysfunction of the solitary tract nucleus and consequently of the baroreflex in acute kidney injury, as well as therapeutic implications, since it encourages work with these drugs in order to mitigate the complications of acute kidney injury in humans,99. Verney C, Legouis D, Voiriot G, Fartoukh M, Labbé V. Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury. J Clin Med. 2021;10(6):1317.

10. Ranucci M, Porta A, Bari V, Pistuddi V, La Rovere MT. Baroreflex sensitivity and outcomes following coronary surgery. PLoS One. 2017 Apr 6;12(4):e0175008.
-1111. Huyut MA. Kidney Injury Molecule-1 Is Associated with Contrast-Induced Nephropathy in Elderly Patients with Non-STEMI. Arq Bras Cardiol. 2021;116(6):1048-56. a clinical situation that denotes an ominous prognosis.1212. Barbosa RR, Cestari PF, Capeletti JT, Peres GM, Ibañez TL, da Silva PV, Farran JA, Amato VL, Farsky PS. Impact of renal failure on in-hospital outcomes after coronary artery bypass surgery. Arq Bras Cardiol. 2011;97(3):249-53. Therefore, this line of research may help understand the treatment in humans with this nosological entity. It is of note that there is evidence of prophylaxis of contrast nephropathy using trimetazidine in humans.1313. Fu H, Zhang J, Zhang H, Zhang P, Fu X, Zeng Z, et al. Trimetazidine can prevent the occurrence of contrast-induced nephropathy after percutaneous coronary intervention in elderly patients with renal insufficiency. Perfusion. 2020;10:267659120957856.,1414. Heshmatzadeh Behzadi A, Amoozgar B, Jain S, Velasco N, Zahid U, Abbasi H, et al. Trimetazidine reduces contrast-induced nephropathy in patients with renal insufficiency undergoing coronary angiography and angioplasty: A systematic review and meta-analysis (PRISMA). Medicine (Baltimore). 2021;100(10):e24603.

  • Short Editorial related to the article: Naringin and Trimetazidine Improve Baroreflex Sensitivity and Nucleus Tractus Solitarius Electrical Activity in Renal Ischemia-Reperfusion Injury

References

  • 1
    Amini N, Sarkaki A, Dianat M, Mard SA, Ahangarpour A, Badavi M. Naringin and Trimetazidine Improve Baroreflex Sensitivity and Nucleus Tractus Solitarius Electrical Activity in Renal Ischemia-Reperfusion Injury. Arq Bras Cardiol. 2021; 117(2):290-297. doi: https://doi.org/10.36660/abc.20200121
    » https://doi.org/10.36660/abc.20200121
  • 2
    Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012;81(10):942-8.
  • 3
    Valenti VE, Ferreira C, Meneghini A, Ferreira M, Murad N, Ferreira Filho C, et al. Evaluation of baroreflex function in Young spontaneously hypertensive rats. Arq Bras Cardiol. 2009;92(3):205-15.
  • 4
    Sousa LE, Favero IFD, Bezerra FS, Souza ABF, Alzamora AC. Environmental Enrichment Promotes Antioxidant Effect in the Ventrolateral Medulla and Kidney of Renovascular Hypertensive Rats. Arq Bras Cardiol. 2019;113(5):905-12.
  • 5
    Guimarães GV, Belli JF, Bacal F, Bocchi EA. Behavior of central and peripheral chemoreflexes in heart failure. Arq Bras Cardiol. 2011;96(2):161-7.
  • 6
    Quarti-Trevano F, Seravalle G, Dell’Oro R, Mancia G, Grassi G. Autonomic Cardiovascular Alterations in Chronic Kidney Disease: Effects of Dialysis, Kidney Transplantation, and Renal Denervation. Curr Hypertens Rep. 2021;23(2):10.
  • 7
    Abdulla MH, Johns EJ. The innervation of the kidney in renal injury and inflammation: a cause and consequence of deranged cardiovascular control. Acta Physiol (Oxf). 2017;220(4):404-16.
  • 8
    Chen WW, Xiong XQ, Chen Q, Li YH, Kang YM, Zhu GQ. Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension. Acta Physiol (Oxf). 2015;213(4):778-94.
  • 9
    Verney C, Legouis D, Voiriot G, Fartoukh M, Labbé V. Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury. J Clin Med. 2021;10(6):1317.
  • 10
    Ranucci M, Porta A, Bari V, Pistuddi V, La Rovere MT. Baroreflex sensitivity and outcomes following coronary surgery. PLoS One. 2017 Apr 6;12(4):e0175008.
  • 11
    Huyut MA. Kidney Injury Molecule-1 Is Associated with Contrast-Induced Nephropathy in Elderly Patients with Non-STEMI. Arq Bras Cardiol. 2021;116(6):1048-56.
  • 12
    Barbosa RR, Cestari PF, Capeletti JT, Peres GM, Ibañez TL, da Silva PV, Farran JA, Amato VL, Farsky PS. Impact of renal failure on in-hospital outcomes after coronary artery bypass surgery. Arq Bras Cardiol. 2011;97(3):249-53.
  • 13
    Fu H, Zhang J, Zhang H, Zhang P, Fu X, Zeng Z, et al. Trimetazidine can prevent the occurrence of contrast-induced nephropathy after percutaneous coronary intervention in elderly patients with renal insufficiency. Perfusion. 2020;10:267659120957856.
  • 14
    Heshmatzadeh Behzadi A, Amoozgar B, Jain S, Velasco N, Zahid U, Abbasi H, et al. Trimetazidine reduces contrast-induced nephropathy in patients with renal insufficiency undergoing coronary angiography and angioplasty: A systematic review and meta-analysis (PRISMA). Medicine (Baltimore). 2021;100(10):e24603.

Publication Dates

  • Publication in this collection
    06 Sept 2021
  • Date of issue
    Aug 2021
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