Toxicokinetics and Metabolism of 3-Monochloropropane 1,2-Diol Dipalmitate in Sprague Dawley Rats

Abstract

Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD) are a group of processing-induced toxicants. To better clarify their possible toxicological effects and mechanisms, it is important to investigate their absorption, distribution, metabolism, and excretion. In this study, the kinetic parameters of 3-MCPD dipalmitate in Sprague Dawley (SD) rat plasma were determined using ultraperformance liquid chromatography–triple quadrupole mass spectrometry. 3-MCPD dipalmitate was absorbed in rats with a C max of 135.00 ng/mL, a T 1/2 of 3.87 h, a T max of 2.5 h, an MRT of 5.08 h, a CL of 3.50 L/h/g, a V d of 21.34 L/g, and an AUC0–∞ of 458.47 h·ng/mL. A total of 17 metabolites were identified, and 16 of them were reported for the first time. Furthermore, these metabolites were examined for their presences in the liver, kidney, testis, brain, spleen, thymus, intestine, plasma, feces, and urine samples 2, 6, 12, 24, and 48 h after oral administration of 3-MCPD dipalmitate using Metabolynx software.

Toxicological assessment of 3‐monochloropropane‐1,2‐diol (3‐MCPD) as a main contaminant of foodstuff in three different in vitro models: Involvement of oxidative stress and cell death signaling pathway

“…To study the effects of 3‐MCPD‐induced cytotoxicity, the experiments were investigated in the framework of the following three different in vitro models: isolated mitochondria from liver and kidney of Wistar rats, HEK‐293 cell line, and liver and kidney cells isolated from rats. Doses or concentrations of 3‐MCPD were selected based on the wide range of 3‐MCPD on HEK cell line as well as the previously published works (Abraham et al., 2013; Huang et al., 2018; Peng et al., 2016). All the doses used in this study exceeded the amounts to which humans are exposed, even more than what is taken through the real diet.…”

“…The mitochondrial isolation process was completely performed at 4 °C in 2 to 3 hr in order to guarantee high‐quality fresh mitochondria needed for determining the release of glutathione (GSH), ferric reducing–antioxidant power (FRAP), malondialdehyde (MDA), and cytochrome c. Fresh isolated mitochondria was incubated in Tris buffer solution for 1 hr at pH 7.4. The concentrations of 3‐MCPD were selected on the basis of either the authors’ pilot dose–response study (data not shown) or previous studies (Cho et al., 2008; Huang et al., 2018; Peng et al., 2016).…”

Diosgenin Protects Against Kidney Injury and Mitochondrial Apoptosis Induced by 3‐MCPD Through the Regulation of ER Stress, Ca2+ Homeostasis, and Bcl2 Expression

“…[ 29 ] Kidney is the most sensitive target of 3‐MCPD exposure. [ 13,30 ] However, far too little data exist concerning the protective effect of DIO, a naturally secondary metabolite of plant, on renal injury induced by 3‐MCPD. In the current study, we aimed at evaluating the protective effect of DIO on kidney injury induced by 3‐MCPD in terms of ER stress, mitochondrial oxidative phosphorylation and apoptosis.…”

Melatonin has favorable preventive effects on experimental chronic pancreatitis rat model

“…In previous studies, caerulein was shown to trigger cell necrosis by inhibition of the Wnt / β-Catenin pathway and lead to increased inflammatory cytokines. In-vivo studies showed that caerulein injection causes edema, inflammation and necrosis in pancreatic acinar cells [13,14].…”