Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice

Abstract

PURPOSE:To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. METHODS: RESULTS:3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. CONCLUSION:3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

Topical 3-bromopyruvate is a novel targeted therapy for melanoma in a preclinical model

“…Although these data are somewhat conflicting, one possible explanation is that 3BP causes concentration-dependent cell death, inducing necrosis at 60 mM and both apoptosis and necrosis at 20-30 mM as described by others [25]. In any case, apoptosis or necrosis, it would be necessary to study the appropriate concentration for the anti-melanoma activity of 3BP, as was demonstrated by the in vivo dose-response analysis in an animal model of liver cancer or breast cancer, which caused significant tumor cell death and minimal toxicity [26,27]. Moreover, further studies are now ongoing to characterize the 3BP-mediated non-apoptotic cell death pathway including necroptosis, pyroptosis, ferroptosis, and autophagic cell death.…”

Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate

“…It has been demonstrated that the antitumor action of 3-BP is accompanied by protective and recuperative effects on immunological, hepatic, and renal homeostasis, with normalization of liver and kidney functions, reduction of tumor growth-associated splenomegaly, restored thymic homeostasis, normalization of blood lymphocytes, and upregulated myelopoiesis (Yadav et al, 2018). Additionally, other studies showed that 3-BP was safe to various tissues (Kunjithapatham et al, 2013; Pan et al, 2016), displaying minimal hepatic and nephrotoxicity (Pan et al, 2016). In Figure 5 , a summary of novel antitumor mechanisms of 3-BP is depicted, showing its ability of multifaceted antitumor action, encompassing aspects such as membrane transport, inhibiting metabolic pathways, pH homeostasis, reconstitution of the TME, declined lipid biosynthesis, mitochondrial stress, restored organ homeostasis, and chemosensitivity.…”

“…Moreover, these limited clinical trials have shown minimal side effects, except minor concerns regarding burning sensation and phlebitis (El Sayed, 2018). Most preclinical and clinical trials report about its safety concerning hepatic functions (Ko et al, 2012; El Sayed et al, 2014; Pan et al, 2016; Yadav et al, 2018). The main recommendations for overcoming the limitations regarding the use of 3-BP include strict implementation of only formulated preparations in human applications (El Sayed, 2018; Fan et al, 2019b), use of GSH scavengers accompanying 3-BP administration because GSH can inactivate 3-BP (El Sayed, 2018), and strict monitoring of the dose regimens (El Sayed, 2018).…”

Construction and Evaluation of Folic Acid-Modified 3-Bromopyruvate Cubosomes

“…In particular, the highly active aerobic glycolysis in a variety of tumor cells acts as a potential target for modern antitumor therapies [ 1 , 2 ]. As one such therapeutic agent, 3-bromopyruvate (3BP) inhibits glycolysis, consequently limiting energy supply to tumor cells and inhibiting their rapid proliferation [ 3 – 7 ]. Studies have found that 3BP enters tumor cells through monocarboxylic acid transporter 1 (MCT1) present on the cell membrane surface [ 8 , 9 ], inhibits the activity of hexokinase II bound to the outer membrane of mitochondria, and consequently limits energy production in cells and inhibits their rapid growth [ 10 – 14 ].…”