Veterinary Research Forum
Vet Res Forum

Effects of histidine and N-acetylcysteine on acute kidney injury induced by doxorubicin in rats: roles of anti-oxidative, anti-inflammatory and anti-apoptotic mechanisms

Document Type : Original Article

Authors

Sanam Mansouri 1
Amir Abbas Farshid 1
Esmaeal Tamaddonfard 2

1 Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

https://doi.org/10.30466/vrf.2024.2040637.4443
Abstract
Doxorubicin (DOX), as a potent anti-cancer agent, exerts side effects in vital organs. Various chemical compounds with tissue protective properties are used to prevent the side effects of DOX. This study was planned to investigate the effects of histidine (HIS) and N-acetylcysteine (NAC) ​​on DOX-induced acute kidney injury. The possible mechanisms were followed by determining the histopathological changes of the kidney along with the biochemical alterations of the blood and kidney tissue. Forty-eight rats were divided into eight groups of six animals each to receive normal saline and DOX after alone and combined treatments with HIS and NAC. The DOX at a single dose of 15.00 mg kg-1 was intraperitoneally injected on day one. The separate and combined intraperitoneally injections of HIS and NAC at a similar dose of 100 mg kg-1 were began 30 min after DOX administration and continued for seven consecutive days. The DOX increased kidney weight and caused congestion, hemorrhages and degeneration in kidney tissue. It also increased serum urea and creatinine concentrations and kidney tissue levels of malondialdehyde, tumor necrosis factor-alpha and caspase-3, and decreased superoxide dismutase activity in this tissue. Separate and combined treatments with HIS and NAC improved all the above-mentioned effects of DOX. The restoring effects of the combined treatment were more prominent than the effect of amino acids alone. It was concluded that anti-oxidative, anti-inflammatory and anti-apoptotic mechanisms might be related to the tissue protective effects of HIS and NAC against DOX-induced acute renal injury.

Keywords

Acute kidney injury
Doxorubicin
Histidine
N-acetylcysteine
Tissue protection

Subjects

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Veterinary Research Forum
Volume 16, Issue 9
September 2025
Pages 507-514

  • Receive Date 09 September 2024
  • Accept Date 05 October 2024

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