Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis
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 injectio...
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| Format: | Article |
| Language: | English |
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Sciendo
2020-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2020-0033 |
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| author | Aljuhani Naif Ismail Raed S. El-Awady Mohammed S. Hassan Memy H. |
| author_facet | Aljuhani Naif Ismail Raed S. El-Awady Mohammed S. Hassan Memy H. |
| author_sort | Aljuhani Naif |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e986f3a9324f4bb1bcabdaf54fbf1d05 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2020-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-e986f3a9324f4bb1bcabdaf54fbf1d052025-02-02T12:01:39ZengSciendoActa Pharmaceutica1846-95582020-12-0170451552510.2478/acph-2020-0033acph-2020-0033Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosisAljuhani Naif0Ismail Raed S.1El-Awady Mohammed S.2Hassan Memy H.3Department of Pharmacology and Toxicology, College of Pharmacy Taibah University, Al-Madinah Al-Munawwarah, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy Al-Azahr University, Cairo, EgyptDepartment of Pharmacology and Toxicology, College of Pharmacy Taibah University, Al-Madinah Al-Munawwarah, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy Taibah University, Al-Madinah Al-Munawwarah, Saudi ArabiaCisplatin-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.https://doi.org/10.2478/acph-2020-0033perindoprilcisplatinnephrotoxicityoxidative stressapoptosisinflammation |
| spellingShingle | Aljuhani Naif Ismail Raed S. El-Awady Mohammed S. Hassan Memy H. Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis Acta Pharmaceutica perindopril cisplatin nephrotoxicity oxidative stress apoptosis inflammation |
| title | Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis |
| title_full | Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis |
| title_fullStr | Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis |
| title_full_unstemmed | Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis |
| title_short | Modulatory effects of perindopril on cisplatin-induced nephrotoxicity in mice: Implication of inflammatory cytokines and caspase-3 mediated apoptosis |
| title_sort | modulatory effects of perindopril on cisplatin induced nephrotoxicity in mice implication of inflammatory cytokines and caspase 3 mediated apoptosis |
| topic | perindopril cisplatin nephrotoxicity oxidative stress apoptosis inflammation |
| url | https://doi.org/10.2478/acph-2020-0033 |
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