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Impaired renal ischemia reperfusion recovery after bilateral renal artery ligation in rats treated with adenine: role of renal mitochondria

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Abstract

Vascular calcification (VC) and ischemia reperfusion (IR) injury is characterised to have mitochondrial dysfunction. However, the impact of dysfunctional mitochondria associated with vascular calcified rat kidney challenged to IR is not explored and is addressed in the present study. Male Wistar rats were treated with adenine for 20 days to induce chronic kidney dysfunction and VC. After 63 days, renal IR protocol was performed with subsequent recovery for 24 h and 7 days. Various mitochondrial parameters and biochemical assays were performed to assess kidney function, IR injury and its recovery. Adenine-induced rats with VC, decreased creatinine clearance (CrCl), and severe tissue injury demonstrated an increase in renal tissue damage and decreased CrCl after 24 h of IR (CrCl in ml: IR-0.220.02, VC-IR-0.050.01). Incidentally, the 24 h IR pathology in kidney was similar in both VC-IR and normal rat IR. But, the magnitude of dysfunction was higher with VC-IR due to pre-existing basal tissue alterations. We found severed deterioration in mitochondrial quantity and quality supported by low bioenergetic function in both VC basal tissue and IR challenged sample. However, post 7 days of IR, unlike normal rat IR, VC rat IR did not improve CrCl and corresponding mitochondrial damage in terms of quantity and its function were observed. Based on the above findings, we conclude that IR in VC rat adversely affect the post-surgical recovery, mainly due to the ineffective renal mitochondrial functional restoration from the surgery.

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Abbreviations

VC:

Vascular calcification

CKD:

Chronic kidney disease

IR:

Ischemia reperfusion

ATP:

Adenosine triphosphate

Al/Cr:

urinary albumin/creatinine ratio

BUN:

Blood urea nitrogen

MDA:

Malondialdehyde

GSH:

Reduced glutathione

GSSG:

Oxidised glutathione

GPx:

Glutathione peroxidase

SOD:

Superoxide dismutase

GR:

Glutathione reductase

NQR:

NADH-oxidoreductase

SQR:

Succinate-coenzyme Q reductase

QCR- QH2:

Cytochrome c oxidoreductase

COX:

Ctochrome c oxidase

PGC-1α:

Peroxisome proliferator-activated receptor-gamma coactivator

Tfam:

transcription regulation factor A

Polg:

Mitochondrial DNA polymeraseγ

Dnm 1:

Dynamin-1

Fis 1:

Mitochondrial fission protein 1

Mff:

Mitochondrial fission factor

Mfn1:

Mitofusin 1

Mfn 2:

Mitofusin 2

Pink:

PTEN- induced kinase 1

Optn:

Optineurin

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Funding

Mrs. Priyanka N Prem sincerely thank the Council of Scientific and Industrial Research, India, for supporting this research through the fellowship grant [09/1095/(0040)/2018-EMR-1].

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Authors and Affiliations

  1. School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, India

    Priyanka N. Prem, David Raj Chellappan & Gino A. Kurian

  2. Vascular Biology lab, School of Chemical and Biotechnology, SASTRA Deemed University, Tirumalaisamudram, Thanjavur, Tamil Nadu, India

    Priyanka N. Prem & Gino A. Kurian

Authors
  1. Priyanka N. Prem
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  2. David Raj Chellappan
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  3. Gino A. Kurian
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Contributions

PNP has processed the experimental data, performed the formal analysis, drafted the manuscript, designed figures & tables, and compiled the literature sources. DRC contributed to the experimental design, execution of the experiment and reviewing the manuscript. GAK has contributed to the design and implementation of the research, to the interpretation of the results, and to the writing of the manuscript.

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Correspondence to Gino A. Kurian.

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The authors declare no competing interests.

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Prem, P.N., Chellappan, D.R. & Kurian, G.A. Impaired renal ischemia reperfusion recovery after bilateral renal artery ligation in rats treated with adenine: role of renal mitochondria. J Bioenerg Biomembr 55, 219–232 (2023). https://doi.org/10.1007/s10863-023-09974-7

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  • DOI: https://doi.org/10.1007/s10863-023-09974-7

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