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Fluvastatin-induced...
Fluvastatin-induced myofibrillar damage is associated with elevated ROS, and impaired fatty acid oxidation, and is preceded by mitochondrial morphological changes
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- Al-Sabri, Mohamed H. (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap,Institutionen för farmaceutisk biovetenskap
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Ammar, Nourhane (author)
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Korzh, Stanislava (author)
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- Alsehli, Ahmed M. (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap,Faculty of Medicine, King Abdulaziz University and Hospital, Al Ehtifalat St., 21589, Jeddah, Saudi Arabia
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- Hosseini, Kimia (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Fredriksson, Robert (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Mwinyi, Jessica (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
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- Williams, Michael J. (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
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Boukhatmi, Hadi (author)
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- Schiöth, Helgi B. (author)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- English.
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- Previously, we showed that fluvastatin treatment induces myofibrillar damage and mitochondrial phenotypes in the skeletal muscles of Drosophila. However, the sequential occurrence of mitochondrial phenotypes and myofibril damage remains elusive. To address this, we treated flies with fluvastatin for two and five days and examined their thorax flight muscles using confocal microscopy. In the two-day fluvastatin group, compared to the control, thorax flight muscles exhibited mitochondrial morphological changes, including fragmentation, rounding up and reduced content, while myofibrils remained organized in parallel. In the five-day fluvastatin treatment, not only did mitochondrial morphological changes become more pronounced, but myofibrils became severely disorganized with significantly increased thickness and spacing, along with myofilament abnormalities, suggesting myofibril damage. These findings suggest that fluvastatin-induced mitochondrial changes precede myofibril damage. Moreover, in the five-day fluvastatin group, the mitochondria demonstrated elevated H2O2 and impaired fatty acid oxidation compared to the control group, indicating potential mitochondrial dysfunction. Surprisingly, knocking down Hmgcr (Drosophila homolog of HMGCR) showed normal mitochondrial respiration in all parameters compared to controls or five-day fluvastatin treatment, which suggests that fluvastatin-induced mitochondrial dysfunction might be independent of Hmgcr inhibition. These results provide insights into the sequential occurrence of mitochondria and myofibril damage in statin-induced myopathy for future studies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- art (subject category)
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- By the author/editor
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Al-Sabri, Mohame ...
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Ammar, Nourhane
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Korzh, Stanislav ...
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Alsehli, Ahmed M ...
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Hosseini, Kimia
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Fredriksson, Rob ...
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show more...
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Mwinyi, Jessica
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Williams, Michae ...
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Boukhatmi, Hadi
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Schiöth, Helgi B ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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Scientific Repor ...
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Uppsala University