Cisplatin and dexamethasone separate and combined effect on nephrotoxic processes in female rats

Zhenya  Yavroyan; Anna Grigoryan; Nune Hakobyan; Agapi Hovhannisyan; Tamara Abgaryan; Anna Karapetyan; Emil Gevorgyan

doi:10.31450/ukrjnd.4(84).2024.08

Zhenya Yavroyan Interfaculty Research Laboratory of Structural Biophysics, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0009-0007-9292-1809
Anna Grigoryan Laboratory of Human and Animal Physiology, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0000-0002-8276-3831
Nune Hakobyan Interfaculty Research Laboratory of Structural Biophysics, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0000-0003-3050-8940
Agapi Hovhannisyan Interfaculty Research Laboratory of Structural Biophysics, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0009-0005-8292-8586
Tamara Abgaryan Laboratory of Human and Animal Physiology, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0009-0000-4159-2725
Anna Karapetyan Laboratory of Human and Animal Physiology, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0000-0001-8869-3187
Emil Gevorgyan Interfaculty Research Laboratory of Structural Biophysics, Research Institute of Biology, Yerevan State University, Yerevan, Republic of Armenia https://orcid.org/0000-0001-8404-7858

DOI: https://doi.org/10.31450/ukrjnd.4(84).2024.08

Keywords: cisplatin, dexamethasone, malondialdehyde, catalase, nephrotoxicity, histological changes.

Abstract

Nephrotoxicity is one of the most severe side effects caused by cisplatin, limiting its use at high, effective concentrations. Dexamethasone, known for its strong anti-inflammatory and immunomodulating properties, is often used to alleviate cisplatin-induced side effects. However, dexamethasone also exhibits pro-oxidant properties and has been associated with morphological impairments and acute kidney injury. Although the mechanisms of cisplatin-induced nephrotoxicity are complex and involve numerous cellular processes, oxidative stress is widely accepted as the primary cause of this pathology. This study aims to investigate how dexamethasone, despite having effects similar to cisplatin, alleviates the side effects caused by this drug.

Methods. The study measured lipid peroxide product malondialdehyde (MDA) levels using the thiobarbituric acid method and catalase activity using the molybdenum method. For histological examination, 5-6 μm thick tissue sections were prepared from samples processed with formalin and fixed with paraffin. These sections were stained with hematoxylin-eosin and observed under a light microscope.

Results. Cisplatin and dexamethasone independently increased MDA levels to varying degrees. Cisplatin raised MDA by 75% in the homogenate and 38% in the supernatant, while dexamethasone increased these levels by 41% and 25%, respectively. The combined use of cisplatin and dexamethasone produced effects similar to those of dexamethasone alone. Catalase activity decreased following exposure to cisplatin (36% in the supernatant and 14% in the nucleus) and dexamethasone alone (33% in the supernatant and 24% in the nucleus). Combined use of the drugs led to a similar reduction in catalase activity. Histological analysis revealed tissue damage, supporting the pro-oxidant nature of both cisplatin and dexamethasone.

Conclusions. The findings indicate that both cisplatin and dexamethasone exhibit pro-oxidant effects, as demonstrated by increased malondialdehyde levels, reduced catalase activity, and histological evidence of tissue damage. The ability of dexamethasone to mitigate cisplatin-induced side effects is likely attributable to a combination of its anti-inflammatory and immunomodulatory properties, as well as a "preventive or restraining" effect.