Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach

Shen, Yunfu; Guo, Kaiqiang; Ma, Ai‐Jun; Huang, Zhe; Du, Jing; Chen, Junhe; Lin, Qianyu; Wei, Chengming; Wang, Zi; Zhang, Fuming; Zhang, Juan; Wu, Lin; Feng, Na; Ma, Wenzhe

doi:10.3389/fphar.2022.1039235

Cited by 2 publications

(1 citation statement)

References 93 publications

(74 reference statements)

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“…Furthermore, cell models cultured at high glucose levels for long periods are not suitable for assessing mitochondrial damage due to switching to glycolysis for energy production (29). Recently developed cell models grown in galactose or without glucose (such as HBSS buffer) and isolated mitochondria can more sensitively and accurately discriminate potential druginduced mitochondrial toxicity (27,30). Therefore, in this study, we focused on primary cells, RPTCs, obtained from kidney tissue with an incubation time of 4 h in HBSS buffer without glucose.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Healthy Mitochondria into Rat Renal Proximal Tubular Cells Reduces Colistin- Induced Mitochondrial Dysfunction and Cellular Damage: An In Vitro Study

Arjmand

Mohammadabadi

Faizi

et al. 2023

Preprint

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Background Kidney damage caused by colistin (polymyxin E) can bring about a decrease in creatinine clearance, potential proteinuria, cylindruria and oliguria in treated patients. It is therefore imperative to develop a new therapeutic strategy for reducing kidney damage after treatment with colistin. Mitochondrial damage is one of contributing factors in colistin-induced nephrotoxicity. Given the therapeutic benefits of mitochondrial transplantation by exogenous healthy mitochondria, we hypothesized that this strategy would be capable of ameliorating renal proximal tubular cells damage following exposure with colistin.Methods For this purpose, we isolated rat renal proximal tubular cells (RPTCs) form kidney and exposed them with toxic concertation of colistin with/without rat healthy isolated mitochondria for 4 hours. Cellular parameters such as lactate dehydrogenase (LDH), reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP), caspase 3 activation, lysosomal damage, glutathione and ATP content were measured.Results The results showed that administration of isolated mitochondria could improve colistin-induced nephrotoxicity and reduce mitochondrial dysfunction. Exogenous mitochondria reduced the activity of LDH, production of ROS, ATP and GSH depletion, loss of MMP, lysosomal damages and cell death.Conclusion To the best of our knowledge, these results provide the first direct experimental evidence that mitochondrial transplantation is capable of ameliorating cellular damage following treatment with colistin. These findings support that mitochondrial transplantation can be a promising therapeutic strategy for colistin-associated mitochondrial dysfunction and kidney damage.

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Section: Discussionmentioning

confidence: 99%

Transplantation of Healthy Mitochondria into Rat Renal Proximal Tubular Cells Reduces Colistin- Induced Mitochondrial Dysfunction and Cellular Damage: An In Vitro Study

Arjmand

Mohammadabadi

Faizi

et al. 2023

Preprint

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Coptisine exerts anti‐tumour effects in triple‐negative breast cancer by targeting mitochondrial complex I

Shen,

Yang,

Wang

et al. 2024

British J Pharmacology

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Background and PurposeTriple‐negative breast cancer (TNBC) has a poor prognosis due to limited therapeutic options. Recent studies have shown that TNBC is highly dependent on mitochondrial oxidative phosphorylation. The aim of this study was to investigate the potential of coptisine, a novel compound that inhibits the complex I of the mitochondrial electron transport chain (ETC), as a treatment for TNBC.Experimental ApproachIn this study, mitochondrial metabolism in TNBC was analysed by bioinformatics. In vitro and in vivo experiments (in mice) were conducted to evaluate the potential of coptisine as an ETC complex I‐targeting therapeutic agent and to investigate the molecular mechanisms underlying coptisine‐induced mitochondrial dysfunction. The therapeutic effect of coptisine was assessed in TNBC cells and xenograft mouse model.Key ResultsWe demonstrated that mitochondrial ETC I was responsible for this metabolic vulnerability in TNBC. Furthermore, a naturally occurring compound, coptisine, exhibited specific inhibitory activity against this complex I. Treatment with coptisine significantly inhibited mitochondrial functions, reprogrammed cellular metabolism, induced apoptosis and ultimately inhibited the proliferation of TNBC cells. Additionally, coptisine administration induced prominent growth inhibition that was dependent on the presence of a functional complex I in xenograft mouse models.Conclusion and ImplicationsAltogether, these findings suggest the promising potential of coptisine as a potent ETC complex I inhibitor to target the metabolic vulnerability of TNBC.

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Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach

Cited by 2 publications

References 93 publications

Transplantation of Healthy Mitochondria into Rat Renal Proximal Tubular Cells Reduces Colistin- Induced Mitochondrial Dysfunction and Cellular Damage: An In Vitro Study

Transplantation of Healthy Mitochondria into Rat Renal Proximal Tubular Cells Reduces Colistin- Induced Mitochondrial Dysfunction and Cellular Damage: An In Vitro Study

Coptisine exerts anti‐tumour effects in triple‐negative breast cancer by targeting mitochondrial complex I

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