Mitochondria-targeted drugs for diabetic kidney disease

Mima, Akira

doi:10.1016/j.heliyon.2022.e08878

Cited by 45 publications

(26 citation statements)

References 80 publications

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“…Notably, different from the action of PF‐06409577, metformin represents an indirect AMPK activator that disturbs mitochondrial complex I of the respiratory chain and suppresses ATP production [ 33 , 34 ], which leads to increased intracellular AMP level and thus AMPK activation [ 33 , 34 , 35 , 36 ]. Metformin also inhibited mitochondrial glycerol 3‐phosphate dehydrogenase, inhibiting NF‐κB, and activating mitophagy through Pink1 and Parkin [ 37 ]. Such mechanism of action is ubiquitous throughout the body, which, as a result, extends beyond the therapeutic role of metformin in ADPKD with potential side effects.…”

Section: Discussionmentioning

confidence: 99%

PF‐06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity

Yuan

Zhang

et al. 2022

FEBS Open Bio

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Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves over‐proliferation of cyst‐lining epithelial cells and excessive cystic fluid secretion. While metformin effectively inhibits renal cyst growth in mouse models of ADPKD it exhibits low potency, and thus an adenosine monophosphate‐activated protein kinase (AMPK) activator with higher potency is required. Herein, we adopted a drug repurposing strategy to explore the potential of PF‐06409577, an AMPK activator for diabetic nephropathy, in cellular, ex vivo and in vivo models of ADPKD. Our results demonstrated that PF‐06409577 effectively down‐regulated mammalian target of rapamycin pathway‐mediated proliferation of cyst‐lining epithelial cells and reduced cystic fibrosis transmembrane conductance regulator‐regulated cystic fluid secretion. Overall, our data suggest that PF‐06409577 holds therapeutic potential for ADPKD treatment.

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Section: Discussionmentioning

confidence: 99%

PF‐06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity

Yuan

Zhang

et al. 2022

FEBS Open Bio

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“…The mechanism of action of Imeglimin is based on restoring the balance in the mitochondrial oxidative-phosphorylation chains, the dysfunction of which causes excessive production of ROS. The result is an increase in mtDNA synthesis and, most importantly, a reduction in oxidative stress by decreasing ROS production [ 76 , 77 ].…”

Section: Pharmacological Therapy Of Diabetes Mellitus and Its Effects...mentioning

confidence: 99%

The Influence of Lifestyle and Treatment on Oxidative Stress and Inflammation in Diabetes

Wronka

Krzemińska

Młynarska

et al. 2022

IJMS

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Diabetes is considered a new pandemic of the modern world, and the number of sufferers is steadily increasing. Sustained hyperglycemia promotes the production of free radicals and leads to persistent, low-grade inflammation. Oxidative stress causes mitochondrial destruction, which along with activation of the hexosamine pathway, nuclear factor-κB (Nf-κb), p38 mitogen-activated protein kinase (p38 MAPK), c-jun NH2 terminal kinase/stress-activated protein kinase (JNK/SAPK) or toll-like receptors (TLRs), leads to pancreatic β-cell dysfunction. However, there is also the protective mechanism that counteracts oxidative stress and inflammation in diabetes, mitophagy, which is a mitochondrial autophagy. An important part of the strategy to control diabetes is to lead a healthy lifestyle based on, among other things, regular physical activity, giving up smoking, eating a balanced diet containing ingredients with antioxidant potential, including vegetables and fruits, and using hypoglycemic pharmacotherapy. Tobacco smoke is a recognized modifiable risk factor for many diseases including diabetes, and it has been shown that the risk of the disease increases in proportion to the intensity of smoking. Physical activity as another component of therapy can effectively reduce glucose fluctuations, and high intensity interval exercise appears to have the most beneficial effect. A proper diet not only increases cellular sensitivity to insulin, but is also able to reduce inflammation and oxidative stress. Pharmacotherapy for diabetes can also affect oxidative stress and inflammation. Some oral drugs, such as metformin, pioglitazone, vildagliptin, liraglutide, and exenatide, cause a reduction in markers of oxidative stress and/or inflammation, while the new drug Imeglimin reverses pancreatic β-cell dysfunction. In studies of sitagliptin, vildagliptin and exenatide, beneficial effects on oxidative stress and inflammation were achieved by, among other things, reducing glycemic excursions. For insulin therapy, no corresponding correlation was observed. Insulin did not reduce oxidative stress parameters. There was no correlation between glucose variability and oxidative stress in patients on insulin therapy. The data used in this study were obtained by searching PubMed online databases, taking into account recent studies.

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“…To fight kidney diseases, numerous therapeutic approaches have been explored [10][11][12][13]. These include exogenous and endogenous compounds, dietary manipulations, modulation of metabolic pathways, stem cell approaches, and cell signaling processes [10,11,[14][15][16][17][18][19][20][21]. In this review article, we will focus on the role of lipoic acid in preventing and ameliorating kidney injuries.…”

Section: Introductionmentioning

confidence: 99%

Renal-Protective Roles of Lipoic Acid in Kidney Disease

Kamt

Liu

2023

Nutrients

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The kidney is a crucial organ that eliminates metabolic waste and reabsorbs nutritious elements. It also participates in the regulation of blood pressure, maintenance of electrolyte balance and blood pH homeostasis, as well as erythropoiesis and vitamin D maturation. Due to such a heavy workload, the kidney is an energy-demanding organ and is constantly exposed to endogenous and exogenous insults, leading to the development of either acute kidney injury (AKI) or chronic kidney disease (CKD). Nevertheless, there are no therapeutic managements to treat AKI or CKD effectively. Therefore, novel therapeutic approaches for fighting kidney injury are urgently needed. This review article discusses the role of α-lipoic acid (ALA) in preventing and treating kidney diseases. We focus on various animal models of kidney injury by which the underlying renoprotective mechanisms of ALA have been unraveled. The animal models covered include diabetic nephropathy, sepsis-induced kidney injury, renal ischemic injury, unilateral ureteral obstruction, and kidney injuries induced by folic acid and metals such as cisplatin, cadmium, and iron. We highlight the common mechanisms of ALA’s renal protective actions that include decreasing oxidative damage, increasing antioxidant capacities, counteracting inflammation, mitigating renal fibrosis, and attenuating nephron cell death. It is by these mechanisms that ALA achieves its biological function of alleviating kidney injury and improving kidney function. Nevertheless, we also point out that more comprehensive, preclinical, and clinical studies will be needed to make ALA a better therapeutic agent for targeting kidney disorders.

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Mitochondria-targeted drugs for diabetic kidney disease

Cited by 45 publications

References 80 publications

PF‐06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity

PF‐06409577 inhibits renal cyst progression by concurrently inhibiting the mTOR pathway and CFTR channel activity

The Influence of Lifestyle and Treatment on Oxidative Stress and Inflammation in Diabetes

Renal-Protective Roles of Lipoic Acid in Kidney Disease

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