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The effects of CORM3 or NaHS on the oxidative stress caused by chronic kidney disease in rats: potential interaction between CO and H2S signaling pathway

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Abstract

Neurotoxicity is implicated as a severe complication of chronic kidney disease (CKD). Accumulation of urea and other toxic compounds leads to oxidative stress, inflammation and destruction of the blood-brain barrier. Carbon monoxide (CO) and hydrogen sulfide (H2S) have been shown to have anti-inflammatory, anti-apoptotic, and anti-proliferative properties. The aims of the present study were evaluated the protective effects of CO-releasing molecule (CORM3) and H2S donor (NaHS) on oxidative stress and neuronal death induced by CKD in the hippocampus and prefrontal cortex by considering interaction between CO and H2S on CBS expression. CORM3 or NaHS significantly compensated deficits in the antioxidant defense mechanisms, suppressed lipid peroxidation and reduced neuronal death in hippocampus and prefrontal cortex and improvement the markers of renal injury that induced by CKD. In addition, CORM3 or NaHS significantly improved CBS expression which were reduced by CKD. However, improving effects of CORM3 on antioxidant defense mechanisms, lipid peroxidation, neuronal death, renal injury and CBS expression were prevented by amino-oxy acetic acid (AOAA) (CBS inhibitor) and reciprocally improving effects of NaHS on all above indices were prevented by zinc protoporphyrin IX (Znpp) (HO-1 inhibitor). In conclusion, this study demonstrated that formation of CO and H2S were interdependently improved CKD-induced oxidative stress and neuronal death, which is may be through increased expression of CBS.

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Abbreviations

AOAA:

Amino-oxy acetic acid

ANOVA:

One-way analysis

BUN:

blood urea nitrogen

CBS:

Cystathionine-β-synthase

CKD:

Chronic kidney disease

CO:

Carbon monoxide

CORM3:

CO-releasing molecule

CNS:

Central nervous system

DG:

Dentate gyrus

GSH:

Glutathione peroxidase

HFD:

High-fat diet

H&E:

Hematoxylin and Eosin

HI:

hypoxic-ischemic

HO-1:

Hemeoxygenase-1

H2S:

Hydrogen sulfide

HTN:

Hypertension

PE:

Preeclampsia

I.C.V:

Intra-cerebro-ventricular

LPS:

Lipopolysaccharide

LTP:

Long-term potentiation

MDA:

Malondialdehyde

MI:

Myocardial infarction

mPFC:

Medial prefrontal cortex

Nrf2:

Nuclear factor erythroid-2-related factor 2

5/6Nx:

5/6 nephrectomy

ROS:

Reactive oxygen species

RVLM:

Rostral ventrolateral medulla

sCr:

Serum creatinine

TBA:

thiobarbituric acid

WB:

Western blot

Znpp:

Zinc protoporphyrin IX

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Funding

This research was supported by a grant (no = 49186) from Tehran University of Medical Sciences.

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Authors and Affiliations

  1. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Zeinab Hamidizad & Behjat Seifi

  2. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Zeinab Hamidizad, Mehri Kadkhodaee, Farzaneh Kianian, Mina Ranjbaran & Behjat Seifi

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  1. Zeinab Hamidizad
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  2. Mehri Kadkhodaee
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  3. Farzaneh Kianian
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  4. Mina Ranjbaran
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zeinab Hamidizad, Mehri Kadkhodaee, Farzaneh Kianian, Mina Ranjbaran, Behjat Seifi1. All authors read and approved the final manuscript.

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Correspondence to Behjat Seifi.

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All processes of dealing with the animals were conducted in accordance with the Animal Ethics Committee of the Faculty of Medicine, Tehran University of Medical Sciences (Approval ID: IR.TUMS.MEDICINE.REC.1399.511).

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The authors declare that they have no conflict of interest. Availability of data and material the data that support the findings of this study are available from the corresponding author upon reasonable request.

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Hamidizad, Z., Kadkhodaee, M., Kianian, F. et al. The effects of CORM3 or NaHS on the oxidative stress caused by chronic kidney disease in rats: potential interaction between CO and H2S signaling pathway. Metab Brain Dis 38, 2653–2664 (2023). https://doi.org/10.1007/s11011-023-01264-w

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