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. 2022 Jun 21;14(7):1313. doi: 10.3390/pharmaceutics14071313

Table 4.

Drugs affecting FA oxidation and TCA cycle, their clinical manifestations, and relevant in vitro and in vivo studies.

Modules Alterations Pharmacology Drugs Clinical Manifestations Cmax Models Dose Time References
FA oxidation Downregulation of FA oxidation related proteins expression Anthracyclines DOX CHF, decreased LVEF, ST, myocarditis, CMP 15.3 μM Male CD-1 mice (IP) 9 mg/kg 1 w [100]
Mitoxantrone CHF, CMP, decreased LVEF, arrhythmia 3.3 μM Male CD-1 mice (IP) 6 mg/kg 1 w [100]
FA oxidation Downregulation of FA oxidation related proteins expression Alkylating agent Cyclophosphamide HMC, CMP 143 μM Male Wistar rats (IP) 200 mg/kg 10 d [189]
TCA cycle Downregulation of TCA related proteins expression Anthracyclines DOX CHF, decreased LVEF, ST, myocarditis, CMP 15.3 μM Male CD-1 mice (IP) 9 mg/kg 1 w [100]
Mitoxantrone CHF, CMP, decreased LVEF, arrhythmia 3.3 μM Male CD-1 mice (IP) 6 mg/kg 1 w [100]
TCA cycle Inhibition of the Krebs cycle enzyme NSAIDs Acetylsalicylate - 0.5–10 mM Isolated rat heart mitochondria Dose response curve [165]
TCA cycle Inhibition of the Krebs cycle enzyme Analgesics Salicylic acid - 0.5–10 mM Isolated rat heart mitochondria Dose response curve [165]
TCA cycle Inhibition of the Krebs cycle enzyme Anthracyclines DOX CHF, decreased LVEF, ST, myocarditis, CMP 15.3 μM Male Wistar rats (IP) 2.5 mg/kg/2 d 2 w [95]
TCA cycle Inhibition of the Krebs cycle enzyme Alkylating agent Cyclophosphamide HMC, CMP 143 μM Male Wistar rats (IP) 200 mg/kg 10 d [124]
Male Wistar rats (IP) 200 mg/kg 10 d [111]
TCA cycle Inhibition of the Krebs cycle enzyme β-adrenoceptor agonists Isoproterenol HF 0.01 μM Male Wistar rats (SC) 100 mg/kg, BID 12 h [83]
TCA cycle Loss of Krebs cycle enzymes Addictive drugs Ethanol Wistar male albino rats 3 g/kg/d 10 d [190]

Abbreviations: FA: fatty acid; TCA: tricarboxylic acid; NRTIs: nucleoside reverse transcriptase inhibitors; NSAIDs: nonsteroidal anti-inflammatory drugs; DOX: doxorubicin; LVEF: left ventricular ejection fraction; HF: heart failure; CHF: congestive hearts failure; CMP: cardiomyopathy; ST: sinus tachycardia; HMC: hemorrhagic myocarditis; IP: intraperitoneal; SC: subcutaneously; BID: twice daily; w: week; d: day; h: hour.