Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats
Abstract Background Some antitumor or anticancer agents have been shown to execute cell death by induction of mitochondrial permeability transition (mPT) pore opening in order to elicit their chemotherapeutic effect. Therefore, this study investigated the effect of metformin on cell death via rat ut...
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SpringerOpen
2021-06-01
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| Series: | Bulletin of the National Research Centre |
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| Online Access: | https://doi.org/10.1186/s42269-021-00562-6 |
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| author | Adeola Oluwakemi Olowofolahan Obinna Matthew Paulinus Heritage Mojisola Dare Olufunso Olabode Olorunsogo |
| author_facet | Adeola Oluwakemi Olowofolahan Obinna Matthew Paulinus Heritage Mojisola Dare Olufunso Olabode Olorunsogo |
| author_sort | Adeola Oluwakemi Olowofolahan |
| collection | DOAJ |
| description | Abstract Background Some antitumor or anticancer agents have been shown to execute cell death by induction of mitochondrial permeability transition (mPT) pore opening in order to elicit their chemotherapeutic effect. Therefore, this study investigated the effect of metformin on cell death via rat uterus mPT pore and estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female rat. Mitochondria were isolated using differential centrifugation. The mPT pore opening, cytochrome c release and mitochondrial ATPase activity were determined spectrophotometrically. Caspases 9 and 3 activities, MDA and estradiol levels and SOD, GSH activities, were determined using ELISA technique. Histological and histochemical assessments of the uterine section were carried out using standard methods. Results Metformin at concentrations 10–90 μg/mL, showed no significant effect on mPT pore opening, mATPase activity and release of cytochrome c. However, oral administration of metformin caused mPT pore opening, enhancement of mATPase activity and activation of caspases 9 and 3 significantly at 300 and 400 mg/kg. Metformin protected against estradiol benzoate (EB)-induced uterine defect and other associated pathophysiological disorder. It also improved the antioxidant defense system. The histological evaluation revealed the protective effect of metformin on the cellular architecture of the uterus while the histochemical examination showed severe hyperplasia in the uterine section of EB-treated rats, remarkably reversed by metformin co-treatment. Conclusion This study suggests that metformin at high doses induces apoptosis via rat uterus mPT pore opening and protects against EB-induced uterine defect (hyperplasia) and associated pathophysiological disorder. |
| first_indexed | 2024-12-20T04:39:40Z |
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| id | doaj.art-7f15412f367c437da306c28e9425f899 |
| institution | Directory Open Access Journal |
| issn | 2522-8307 |
| language | English |
| last_indexed | 2024-12-20T04:39:40Z |
| publishDate | 2021-06-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Bulletin of the National Research Centre |
| spelling | doaj.art-7f15412f367c437da306c28e9425f8992022-12-21T19:53:09ZengSpringerOpenBulletin of the National Research Centre2522-83072021-06-014511910.1186/s42269-021-00562-6Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar ratsAdeola Oluwakemi Olowofolahan0Obinna Matthew Paulinus1Heritage Mojisola Dare2Olufunso Olabode Olorunsogo3Laboratory for Membrane Biochemistry Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanLaboratory for Membrane Biochemistry Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanLaboratory for Membrane Biochemistry Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanLaboratory for Membrane Biochemistry Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of IbadanAbstract Background Some antitumor or anticancer agents have been shown to execute cell death by induction of mitochondrial permeability transition (mPT) pore opening in order to elicit their chemotherapeutic effect. Therefore, this study investigated the effect of metformin on cell death via rat uterus mPT pore and estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female rat. Mitochondria were isolated using differential centrifugation. The mPT pore opening, cytochrome c release and mitochondrial ATPase activity were determined spectrophotometrically. Caspases 9 and 3 activities, MDA and estradiol levels and SOD, GSH activities, were determined using ELISA technique. Histological and histochemical assessments of the uterine section were carried out using standard methods. Results Metformin at concentrations 10–90 μg/mL, showed no significant effect on mPT pore opening, mATPase activity and release of cytochrome c. However, oral administration of metformin caused mPT pore opening, enhancement of mATPase activity and activation of caspases 9 and 3 significantly at 300 and 400 mg/kg. Metformin protected against estradiol benzoate (EB)-induced uterine defect and other associated pathophysiological disorder. It also improved the antioxidant defense system. The histological evaluation revealed the protective effect of metformin on the cellular architecture of the uterus while the histochemical examination showed severe hyperplasia in the uterine section of EB-treated rats, remarkably reversed by metformin co-treatment. Conclusion This study suggests that metformin at high doses induces apoptosis via rat uterus mPT pore opening and protects against EB-induced uterine defect (hyperplasia) and associated pathophysiological disorder.https://doi.org/10.1186/s42269-021-00562-6ApoptosisCancerMetforminMitochondriaMitochondrial permeability transition pore |
| spellingShingle | Adeola Oluwakemi Olowofolahan Obinna Matthew Paulinus Heritage Mojisola Dare Olufunso Olabode Olorunsogo Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats Bulletin of the National Research Centre Apoptosis Cancer Metformin Mitochondria Mitochondrial permeability transition pore |
| title | Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats |
| title_full | Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats |
| title_fullStr | Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats |
| title_full_unstemmed | Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats |
| title_short | Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats |
| title_sort | metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate induced uterine defect and associated pathophysiological disorder in female wistar rats |
| topic | Apoptosis Cancer Metformin Mitochondria Mitochondrial permeability transition pore |
| url | https://doi.org/10.1186/s42269-021-00562-6 |
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