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414128

Activation of angiotensin-converting enzyme 2 mitigates Doxorubicin induced nephrotoxicity by TLR4/NF-kB downregulation

Article

Last updated: 11 May 2025

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Subjects

-

Tags

Experimental Toxicology

Abstract

The application of the anticancer antibiotic doxorubicin (Dox) has been limited due to the emergence of toxicities affecting vital organs, including the kidneys. The anti-trypanosomal drug diminazene aceturate (DIZE) was found to activate ACE2 and have multiple protective advantages. This study sought to elucidate the probable mechanisms and renoprotective benefits of DIZE in DOX-induced nephrotoxicity. Thirty male albino rats were divided into three groups: DOX, DOX+DIZE, and control groups, with ten rats in each category. After 8 weeks serum urea, serum creatinine, urine albumin, creatinine clearance, renal angiotensin II, renal angiotensin-converting enzyme 2, renal malondialdehyde, renal superoxide dismutase, renal tumor necrosis factor-alpha, renal interleukin-6, and renal gene expression of nuclear factor kappa B and Toll-like receptor 4 were assessed. Supplementary assessments of NF-kB and TLR4 immunoreactivity in the kidney were conducted. In the DOX group, serum levels of urea and creatinine, along with urinary albumin, renal MDA, renal TNF-α, renal IL-6, renal Ang II, and the renal gene expression and immune-reactivity of TLR4 and NF-κB, were significantly elevated compared to the control group; conversely, renal SOD, creatinine clearance, and renal ACE2 values in the DOX group were markedly diminished relative to the control. DIZE significantly improved the alterations caused by DOX-induced nephrotoxicity. DIZE affords renoprotection in DOX rats by downregulating the renal TLR4–NF-kB pathway and acting as an ACE2 activator, hence modifying the kidneys' anti-inflammatory and antioxidant properties

DOI

10.21608/mjfmct.2025.353763.1095

Keywords

ACE2 Diminazene, Doxorubicin NF-kB, Nephrotoxicity, TLR4

Authors

First Name

Suzan

Last Name

Khodir

MiddleName

A

Affiliation

Physiology Department, Faculty of Medicine, Menoufia University, Egypt

Email

suzan.abdalhameed.12@med.menofia.edu.eg

City

Menoufia

Orcid

0000-0002-2535-9445

First Name

Sara

Last Name

Abdelrahman

MiddleName

Elsayed

Affiliation

Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Ain Shams University, Egypt

Email

sara.abdelrahman@med.asu.edu.eg

City

-

Orcid

-

First Name

noha

Last Name

Abd El-aziz

MiddleName

-

Affiliation

Anatomy and Embryology Department, Faculty of Medicine, Menoufia University

Email

rose_a.hashem256@yahoo.com

City

-

Orcid

-

First Name

Yasmin

Last Name

Aboul-Ela

MiddleName

M

Affiliation

Clinical Pharmacology Department, Faculty of medicine, Ain Shams University, Egypt.

Email

dr.yasmin.mahmoud@med.asu.edu.eg

City

-

Orcid

-

First Name

Sara

Last Name

Khedr

MiddleName

A

Affiliation

Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Egypt

Email

drsara_khedr@med.asu.edu.eg

City

-

Orcid

-

First Name

Eman

Last Name

El-Sawaf

MiddleName

A

Affiliation

Anatomy and Embryology Department, Faculty of Medicine, Helwan University Egypt

Email

eman.elsawaf@med.helwan.edu.eg

City

-

Orcid

0000-0003-3501-2661

First Name

Soha

Last Name

Abd EL-Khalek

MiddleName

H

Affiliation

Forensic Medicine and Clinical Toxicology department, Faculty of Medicine, Menoufia University

Email

d_sh_2007@yahoo.com

City

-

Orcid

-

First Name

Menna Allah

Last Name

El Menyawi

MiddleName

I

Affiliation

Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt

Email

soso_egy98@yahoo.com

City

-

Orcid

-

First Name

Walaa

Last Name

Yusuf

MiddleName

Ahmed

Affiliation

Pathology Department, Faculty of Medicine, Mansoura University, Egypt.

Email

suzy25186@yahoo.com

City

-

Orcid

-

First Name

Mohamed

Last Name

Greash

MiddleName

Ahmed

Affiliation

Internal Medicine Department, Faculty of Medicine, Suez Canal University

Email

suzy25186@gmail.com

City

-

Orcid

-

First Name

Noha

Last Name

Shawky

MiddleName

O

Affiliation

Medical Physiology Department, Faculty of Medicine, Helwan University, Egypt.

Email

noha.osama@med.helwan.edu.eg

City

-

Orcid

-

Volume

33

Article Issue

2

Related Issue

51129

Issue Date

2025-07-01

Receive Date

2025-01-20

Publish Date

2025-07-01

Page Start

1

Page End

11

Print ISSN

1110-5437

Online ISSN

2682-3217

Article File

MJFMCT_Volume 33_Issue 2_Pages 1-11.pdf

PDF . 1.0MB

Link

https://mjfmct.journals.ekb.eg/article_414128.html

Detail API

http://journals.ekb.eg?_action=service&article_code=414128

Order

414,128

Type

Original Article

Type Code

966

Publication Type

Journal

Publication Title

Mansoura Journal of Forensic Medicine and Clinical Toxicology

Publication Link

https://mjfmct.journals.ekb.eg/

MainTitle

Activation of angiotensin-converting enzyme 2 mitigates Doxorubicin induced nephrotoxicity by TLR4/NF-kB downregulation

Details

Type

Article

Created At

11 May 2025