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Organ-protective effects on the liver and kidney by minocycline in small piglets undergoing cardiopulonary bypass

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Abstract

Cardiopulmonary bypass (CPB) often is required for the operative correction of congenital heart defects in small infants. Unfortunately, CPB is associated with injury of inner organs such as the brain, kidney, lung, and liver. Renal failure and increase in liver enzymes are typical side effects observed after CPB. Here, we investigate whether organ protection of the kidney and liver can be achieved with the application of minocycline, which is known—besides its anti-infective effects—to act as a poly-ADP-ribose-polymerase inhibitor. Twenty-nine 4-week-old Angler Sattelschwein-piglets (8–15 kg) were divided into four groups: control group (n = 8), CPB group (n = 9), minocycline-control group (n = 6), and the minocycline-CPB group (n = 6). CPB groups were thoracotomized and underwent CPB for 120 min (cross-clamp, 90 min; reperfusion, 30 min) followed by a 90-min recovery time. The control groups also were thoracotomized but not connected to CPB. The minocycline group received 4 mg/kg minocycline before and 2 mg/kg after CPB. In the kidneys, CPB histologically resulted in widening of Bowman’s capsule, and—mainly in tubules—formation of poly-ADP-ribose, nitrosylation of tyrosine-residues, nuclear translocation of hypoxia-induced factor HIF-1α, and of apoptosis-inducing factor (AIF). In addition, we found significantly less ATP in the kidney and significantly increased plasma urea and creatinine. Similar but gradually attenuated changes were found in the liver together with significantly elevated de-Ritis coefficient. These changes in the kidney and liver were significantly diminished by minocycline (except AIF in the liver which was similar in all groups). In conclusion, CPB causes damage in the kidney and—to a lower degree—in the liver, which can be attenuated by minocycline.

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Abbreviations

AEC:

3-Amino-9-ethylcarbazol

AIF:

Apoptosis inducing factor

ALT:

Alanine-aminotransferase

AST:

Aspartate-aminotransferase

BSA:

Bovine serum albumin

CPB:

Cardiopulmonary bypass

DAB:

3,3′-Diaminobenzidine

HE:

Hematoxylin eosin

HIF:

Hypoxia-inducible factor

HPLC:

High-performance liquid chromatography

PAR:

Poly-ADP-ribose

PARP:

Poly-ADP-ribose-polymerase

PBS:

Phosphate-buffered saline

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Acknowledgments

This study has been supported by a grant given by ProCordis (Leipzig, Germany) to S.D.

Conflict of interest

The authors declare no competing interests.

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Authors and Affiliations

  1. Clinic for Cardiac Surgery, University of Leipzig, Heart Centre, Leipzig, Germany

    Stefan Dhein, Maria Gerdom, Marcel Vollroth, Farhad Bakhtiary, Sandy von Salisch, Klaus Krämer, Martin Kostelka & Friedrich-Wilhelm Mohr

  2. Ambulatorische und Geburtshilfliche Tierklinik, University of Leipzig, Leipzig, Germany

    Axel Sobiraj

  3. Clinic for Paediatric Cardiology, University of Leipzig, Heart Centre, Leipzig, Germany

    Maria Grassl & Aida Salameh

Authors
  1. Stefan Dhein
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  2. Maria Grassl
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  3. Maria Gerdom
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  4. Marcel Vollroth
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  5. Farhad Bakhtiary
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  6. Sandy von Salisch
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  10. Friedrich-Wilhelm Mohr
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  11. Aida Salameh
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Correspondence to Stefan Dhein.

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Dhein, S., Grassl, M., Gerdom, M. et al. Organ-protective effects on the liver and kidney by minocycline in small piglets undergoing cardiopulonary bypass. Naunyn-Schmiedeberg's Arch Pharmacol 388, 663–676 (2015). https://doi.org/10.1007/s00210-015-1115-4

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  • DOI: https://doi.org/10.1007/s00210-015-1115-4

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