<abstract xmlns="http://www.w3.org/1999/xhtml">Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study’s aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg−1, <italic>i.p.</italic>) and perindopril was administered orally (2 mg kg−1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress.</abstract>

Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study’s aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg−1, i.p.) and perindopril was administered orally (2 mg kg−1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress.

Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

Department of Pharmacology and Toxicology

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study’s aim was to assess the potential modulatory effect of perindopril on...

Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

Published Online: May 13, 2020

Page range: 515 - 525

Accepted: Nov 18, 2019

DOI: https://doi.org/10.2478/acph-2020-0033

Keywords
perindopril, cisplatin, nephrotoxicity, oxidative stress, apoptosis, inflammation

© 2020 Naif Aljuhani et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis

Published Online: May 13, 2020

Page range: 515 - 525

Accepted: Nov 18, 2019

DOI: https://doi.org/10.2478/acph-2020-0033

Keywordsperindopril, cisplatin, nephrotoxicity, oxidative stress, apoptosis, inflammation

© 2020 Naif Aljuhani et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
perindopril, cisplatin, nephrotoxicity, oxidative stress, apoptosis, inflammation