Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats
Background: Endothelin-1 (ET-1) is a vasoconstrictor peptide that mediates cell proliferation, fibrosis, and inflammation. ET-1 has 2 receptors A and B. Objectives: The present study investigated whether administration of ET-1 receptor type A antagonist leads to protect cisplatin (CP) induced nephr...
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| Format: | Article |
| Language: | English |
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Society of Diabetic Nephropathy Prevention
2015-10-01
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| Series: | Journal of Nephropathology |
| Subjects: | |
| Online Access: | https://nephropathol.com/PDF/JNP-4-134.pdf |
| _version_ | 1797827957562015744 |
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| author | Alieh Zahedi Mehdi Nematbakhsh Maryam Moeini Ardeshir Talebi |
| author_facet | Alieh Zahedi Mehdi Nematbakhsh Maryam Moeini Ardeshir Talebi |
| author_sort | Alieh Zahedi |
| collection | DOAJ |
| description | Background: Endothelin-1 (ET-1) is a vasoconstrictor peptide that mediates cell proliferation, fibrosis, and inflammation. ET-1 has 2 receptors A and B. Objectives: The present study investigated whether administration of ET-1 receptor type A antagonist leads to protect cisplatin (CP) induced nephrotoxicity in ovariectomized-estradiol (Es) treated rats. Materials and Methods: Thirty-six ovariectomized Wistar rats were divided into 6 groups. Group 1 received CP (2.5 mg/kg/day) for one week. Groups 2 and 3 received 2 different doses of Es (0.25 and 0.5 mg/kg/week) for 3 weeks, but CP was started in the third week. Group 4 was treated as group 1, but bosentan (BOS, 30 mg/kg/day) was also added. Groups 5 and 6 treated similar to groups 2 and 3 but CP and BOS were added in the third week. At the end of the experiment, blood samples were obtained, and the animals were sacrificed for histopathological investigation of kidney tissue. Results: The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) increased by CP; however, BOS significantly elevated the BUN and Cr levels that were increased by CP administration (P < 0.05). Co-treatment of Es, BOS, and CP decreased the serum levels of BUN, Cr, and malondialdehyde (MDA) when compared with the group treated with BOS plus CP (P < 0.05). Such finding was obtained for kidney tissue damage score (KTDS). As expected, Es significantly increased uterus weight (P < 0.05). The groups were not significantly different in terms of serum and kidney nitrite, kidney weight (KW), and bodyweight Conclusions: According to our findings, BOS could not protect renal functions against CP-induced nephrotoxicity. In contrast, Es alone or accompanied with BOS could protect the kidney against CP-induced nephrotoxicity via reduction of BUN, Cr, and KTDS. |
| first_indexed | 2024-04-09T12:56:44Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2251-8363 2251-8819 |
| language | English |
| last_indexed | 2024-04-09T12:56:44Z |
| publishDate | 2015-10-01 |
| publisher | Society of Diabetic Nephropathy Prevention |
| record_format | Article |
| series | Journal of Nephropathology |
| spelling | doaj.art-1520f1fe376746828c5431758e3e02d82023-05-13T11:34:00ZengSociety of Diabetic Nephropathy PreventionJournal of Nephropathology2251-83632251-88192015-10-014413414010.12860/jnp.2015.25JNP_20151006211051Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated ratsAlieh Zahedi0Mehdi Nematbakhsh1Maryam Moeini2Ardeshir Talebi3Water & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IranWater & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IranWater & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IranWater & Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IranBackground: Endothelin-1 (ET-1) is a vasoconstrictor peptide that mediates cell proliferation, fibrosis, and inflammation. ET-1 has 2 receptors A and B. Objectives: The present study investigated whether administration of ET-1 receptor type A antagonist leads to protect cisplatin (CP) induced nephrotoxicity in ovariectomized-estradiol (Es) treated rats. Materials and Methods: Thirty-six ovariectomized Wistar rats were divided into 6 groups. Group 1 received CP (2.5 mg/kg/day) for one week. Groups 2 and 3 received 2 different doses of Es (0.25 and 0.5 mg/kg/week) for 3 weeks, but CP was started in the third week. Group 4 was treated as group 1, but bosentan (BOS, 30 mg/kg/day) was also added. Groups 5 and 6 treated similar to groups 2 and 3 but CP and BOS were added in the third week. At the end of the experiment, blood samples were obtained, and the animals were sacrificed for histopathological investigation of kidney tissue. Results: The serum levels of creatinine (Cr) and blood urea nitrogen (BUN) increased by CP; however, BOS significantly elevated the BUN and Cr levels that were increased by CP administration (P < 0.05). Co-treatment of Es, BOS, and CP decreased the serum levels of BUN, Cr, and malondialdehyde (MDA) when compared with the group treated with BOS plus CP (P < 0.05). Such finding was obtained for kidney tissue damage score (KTDS). As expected, Es significantly increased uterus weight (P < 0.05). The groups were not significantly different in terms of serum and kidney nitrite, kidney weight (KW), and bodyweight Conclusions: According to our findings, BOS could not protect renal functions against CP-induced nephrotoxicity. In contrast, Es alone or accompanied with BOS could protect the kidney against CP-induced nephrotoxicity via reduction of BUN, Cr, and KTDS.https://nephropathol.com/PDF/JNP-4-134.pdfcisplatinestradiolnephrotoxicitybosentanrat |
| spellingShingle | Alieh Zahedi Mehdi Nematbakhsh Maryam Moeini Ardeshir Talebi Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats Journal of Nephropathology cisplatin estradiol nephrotoxicity bosentan rat |
| title | Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats |
| title_full | Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats |
| title_fullStr | Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats |
| title_full_unstemmed | Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats |
| title_short | Role of endothelin receptor antagonist; bosentan in cisplatin-induced nephrotoxicity in ovariectomized estradiol treated rats |
| title_sort | role of endothelin receptor antagonist bosentan in cisplatin induced nephrotoxicity in ovariectomized estradiol treated rats |
| topic | cisplatin estradiol nephrotoxicity bosentan rat |
| url | https://nephropathol.com/PDF/JNP-4-134.pdf |
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