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Mitochondrial Transplantation Alleviates Doxorubicin-Induced Toxicity in Rat Renal Cells
Enayatollah Seydi1,2, Mahsa Andalib3, Sana Yaghoubi4
1Department of Occupational Health and Safety Engineering, School of Health, Alborz University of Medical Sciences, Karaj, Iran.
Background:
Doxorubicin (DOX) is used in the treatment of various cancers and has good effectiveness. However, its therapeutic use is limited due to its effects on various organs and healthy cells. Doxorubicin can affect the kidneys and cause toxicity. Evidence shows that DOX induces nephrotoxicity through oxidative stress.
Objectives:
In this research, we examined the effect of mitochondrial transplantation on improving mitochondrial and cellular toxicity caused by DOX on renal proximal tubular cells (RPTCs).
Methods:
The research measured 7 toxicity parameters, including cell lysis, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) decline, GSH and GSSG content, lipid peroxidation (LPO), adenosine triphosphate (ATP) content, and Caspase-3 activity (the final mediator of apoptosis). Active fresh mitochondria were prepared from Wistar rat kidney.
Results:
The findings indicated that DOX caused cytotoxicity in RPTCs. Additionally, DOX induced oxidative stress by increasing the level of reactive oxygen species, reducing glutathione content, and elevating lipid peroxidation. Moreover, it led to damage to the mitochondrial membrane, increased caspase-3 activity, and decreased ATP content. Mitochondrial transplantation, as a new therapeutic approach, reduced oxidative stress, mitochondrial membrane damage, and apoptosis caused by DOX in RPTCs. Furthermore, this therapeutic approach increased the ATP content in RPTCs.
Conclusions:
Our study suggests that this therapeutic approach could be helpful in the treatment of drug-induced nephrotoxicity.
Insights
Mitochondrial transplantation may protect kidney cells from doxorubicin-induced toxicity. This novel approach reduced oxidative stress and apoptosis, offering a potential treatment for drug-induced nephrotoxicity.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Doxorubicin (DOX) is an effective anti-cancer drug but causes kidney toxicity (nephrotoxicity) via oxidative stress.
- This limits its therapeutic application, necessitating strategies to mitigate its adverse effects on renal proximal tubular cells (RPTCs).
Purpose of the Study:
- To investigate the efficacy of mitochondrial transplantation in ameliorating DOX-induced mitochondrial and cellular toxicity in RPTCs.
- To evaluate the protective effects of this novel therapeutic strategy against DOX-induced nephrotoxicity.
Main Methods:
- RPTCs were treated with DOX, and toxicity was assessed by measuring cell lysis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), glutathione (GSH/GSSG) levels, lipid peroxidation (LPO), adenosine triphosphate (ATP) content, and Caspase-3 activity.
- Active mitochondria were isolated from Wistar rat kidneys for transplantation experiments.
Main Results:
- DOX induced significant cytotoxicity in RPTCs, characterized by increased ROS, LPO, and Caspase-3 activity, alongside decreased MMP, GSH, and ATP levels.
- Mitochondrial transplantation effectively counteracted DOX-induced toxicity by reducing oxidative stress, mitochondrial damage, and apoptosis.
- This approach also restored ATP content in DOX-treated RPTCs.
Conclusions:
- Mitochondrial transplantation demonstrates significant potential as a therapeutic strategy to combat doxorubicin-induced nephrotoxicity.
- This method offers a promising avenue for protecting renal cells from drug-induced damage and improving patient outcomes in cancer therapy.
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