Document Type : Original Article
Authors
1
Physiology Department, Faculty of Medicine, Menoufia University, Egypt
2
Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Ain Shams University, Egypt
3
Anatomy and Embryology Department, Faculty of Medicine, Menoufia University
4
Clinical Pharmacology Department, Faculty of medicine, Ain Shams University, Egypt.
5
Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Egypt
6
Anatomy and Embryology Department, Faculty of Medicine, Helwan University Egypt
7
Forensic Medicine and Clinical Toxicology department, Faculty of Medicine, Menoufia University
8
Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
9
Pathology Department, Faculty of Medicine, Mansoura University, Egypt.
10
Internal Medicine Department, Faculty of Medicine, Suez Canal University
11
Medical Physiology Department, Faculty of Medicine, Helwan University, Egypt.
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
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