Inhibition of hepatic energy metabolizing enzymes in murine model exposed to diisononyl phthalate
Keywords:diisononyl phthalate, liver, oxidative phosphorylation, phthalates
Background and objectives: Diisononyl phthalate (DINP) is a class of phthalates and phthalates are known to be metabolism disrupting chemicals (MDCs). Numerous MDCs, to which humans are exposed, have an effect on every aspect of energy transduction. They affect the liver by impairing insulin secretion in pancreatic cells and altering the liver’s insulin-dependent glucose metabolism.
Methods: For this study, eighteen male albino rats weighing 200±20g were randomly assigned to three groups (of six rats each) and followed for a 14-days period. The groups were: group A or control which was given Tween-80 orally, group B or DINP1 group which was given 20 mg/kg b.wt. DINP, and Group C or DINP2 group which received 200 mg/kg b.wt. DINP. The rats were then sacrificed, their livers were removed, and the glycolytic and oxidative phosphorylation enzyme activities were evaluated.
Results: Activities of the glycolytic, tricarboxylic acid cycle and electron transport chain enzymes under investigation were significantly down-regulated with severity observed in decreased activities of hepatic oxidative phosphorylation enzymes when compared with control (P<0.05). Hepatic tissue sections of 20 and 200mg/kg DiNP group revealed distorted cytoarchitecture of hepatocytes ranging from histocellular disarrangement to vaocular changes suggestive of loss of liver integrity or fibrosis.
Conclusions: Finally, DINP exposure impairs hepatic energy transduction enzymes as evident in down-regulation of the various enzymes of energy metabolism under investigation and this may invariably be a good tool for the diagnosis of hepatic energy impairment as seen in some disease conditions.
A G Gornall, C J Bardawill, and M M David. “Determination of serum proteins by means of the biuret reaction”. J Biol Chem 177(18) (1949), pp. 751–766. DOI: https://doi.org/10.1016/S0021-9258(18)57021-6
A H Fischer et al. “Hematoxylin and eosin staining of tissue and cell sections”. CSH Protoc (2008), pp. 4986–4986. DOI: 10.1101/pdb.prot4986. DOI: https://doi.org/10.1101/pdb.prot4986
A Nadal et al. “Endocrine-disrupting chemicals and the regulation of energy balance”. Nat Rev Endocrinol 13(9) (2017), pp. 536–582. DOI: 10.1038/nrendo.2017.51. DOI: https://doi.org/10.1038/nrendo.2017.51
A Ore et al. “Potential roles of oxidative stress and insulin resistance in diisononyl phthalate induced dyslipidemia and hepatosteatosis in BALB/c mice”. Adv Redox Res 5 (2022), pp. 100038–100038. DOI: 10.1016/j.arres.2022.100038. DOI: https://doi.org/10.1016/j.arres.2022.100038
A Y Romkina and M Y Kiriukhin. “Biochemical and molecular characterization of the isocitrate dehydrogenase with dual coenzyme specificity from the obligate methylotroph Methylobacillus Flagellatus”. Plos one 12(4) (2017), e0176056–e0176056. DOI: 10.1371/journal.pone.0176056. DOI: https://doi.org/10.1371/journal.pone.0176056
D V Dervartanian and C Veeger. “Studies on succinate dehydrogenase: I. Spectral properties of the purified enzyme and formation of enzyme-competitive inhibitor complexes”. Biochim Biophys Acta 92(2) (1964), pp. 233–247. DOI: https://doi.org/10.1016/0926-6569(64)90182-8
E Fernández-Vizarra et al. “Isolation of mitochondria for biogenetical studies: An update”. Mitochondrion 10(3) (2010), pp. 253–262. DOI: 10.1016/j.mito.2009.12.148. DOI: https://doi.org/10.1016/j.mito.2009.12.148
F Kracke, I Vassilev, and J O Krömer. “Microbial electron transport and energy conservation-the foundation for optimizing bioelectrochemical systems”. Front Microbiol 6 (2015), pp. 575–575. DOI: 10.3389/fmicb.2015.00575. DOI: https://doi.org/10.3389/fmicb.2015.00575
F Medja et al. “Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis”. Mitochondrion 9(5) (2009), pp. 331–340. DOI: 10.1016/j.mito.2009.05.001. DOI: https://doi.org/10.1016/j.mito.2009.05.001
G Rajagopal, R S Bhaskaran, and B Karundevi. “Maternal di-(2-ethylhexyl) phthalate exposure alters hepatic insulin signal transduction and glucoregulatory events in rat F1 male offspring”. J Appl Toxicol 39(5) (2019), pp. 751–763. DOI: 10.1002/jat.3764. DOI: https://doi.org/10.1002/jat.3764
I Tatsuno et al. “Characterization of the NAD-glycohydrolase in streptococcal strains”. Microbiology 153(12) (2007), pp. 4253–4260. DOI: 10.1099/mic.0.2007/009555-0. DOI: https://doi.org/10.1099/mic.0.2007/009555-0
J J Briere et al. “Succinate dehydrogenase deficiency in human”. Cell Mol Life Sci 62 (2005), pp. 2317–2324. DOI: 10.1007/s00018-005-5237-6. DOI: https://doi.org/10.1007/s00018-005-5237-6
L Rui. “Energy metabolism in the liver”. Compr Physiol 4(1) (2014), pp. 177–97. DOI: 10.1002/cphy.c130024. DOI: https://doi.org/10.1002/cphy.c130024
N R Sims and J B Blass. “Phosphofructokinase activity in fibroblasts from patients with Alzheimer’s disease and age- and sex matched controls”. Metab Brain Dis 1(1) (1986), pp. 83–90. DOI: 10.1007/BF00998479. DOI: https://doi.org/10.1007/BF00998479
National Research Council. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, D.C: National academy press, 1996.
P E López-Calcagno et al. “Cloning, expression and biochemical characterization of mitochondrial and cytosolic malate dehydrogenase from Phytophthora infestans”. Mycol Res 113(6-7) (2009), pp. 771–781. DOI: 10.1016/j.mycres.2009.02.012. DOI: https://doi.org/10.1016/j.mycres.2009.02.012
P Ma et al. “Oral exposure of Kunming mice to diisononyl phthalate induces hepatic and renal tissue injury through the accumulation of ROS. Protective effect of melatonin”. Food Chem Toxicol 1(68) (2014), pp. 247–56. DOI: 10.1016/j.fct.2014.03.027. DOI: https://doi.org/10.1016/j.fct.2014.03.027
P Sharma and H Sampath. “Mitochondrial DNA integrity: role in health and disease”. Cells 8(2) (2019), pp. 100–100. DOI: 10.3390/cells8020100. DOI: https://doi.org/10.3390/cells8020100
S A Kehinde et al. “Diisononyl phthalate inhibits cardiac glycolysis and oxidative phosphorylation by down-regulating cytosolic and mitochondrial energy metabolizing enzymes in murine model”. Adv Redox Res 6 (2022), pp. 100041–100041. DOI: 10.1016/j.arres.2022.100041. DOI: https://doi.org/10.1016/j.arres.2022.100041
S A Kehinde et al. “Diisononyl phthalate negatively perturbs testicular energy metabolism and histoarchitecture of rats”. Journal of Hazardous Materials Advances 28 (2022), pp. 100153–100153. DOI: https://doi.org/10.1016/j.hazadv.2022.100153
S P Colowick and. “The hexokinases”. In: The Enzymes. Vol. 9. Academic Press, 1973, pp. 60113–60117. DOI: 10.1016/S1874-6047(08)60113-4. DOI: https://doi.org/10.1016/S1874-6047(08)60113-4
S Saeidnia. “Phthalates”. In: Encyclopedia of Toxicology. Ed. by P. Wexler. Vol. 3. Oxford: Academic Press, 2014, pp. 928–933. DOI: 10.1016/B978-0-12-386454-3.00963-5. DOI: https://doi.org/10.1016/B978-0-12-386454-3.00963-5
V Jagannathan, K Singh, and M Damodaran. “Carbohydrate metabolism in citric acid fermentation. Purification and properties of aldolase from Aspergillus niger”. Biochem J 63 (1956), pp. 94–94. DOI: 10.1042/bj0630094. DOI: https://doi.org/10.1042/bj0630094
X Dong et al. “Urinary metabolomic profiling in rats exposed to dietary di(2-ethylhexyl) phthalate (DEHP) using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS)”. Environ Sci Pollut Res Int 24(20) (2017), pp. 16659–16672. DOI: 10.1007/s11356-017-9091-5. DOI: https://doi.org/10.1007/s11356-017-9091-5
X Yu et al. “Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)”. Cardiovasc Diabetol 6(1) (2007), pp. 1–8. DOI: 10.1186/1475-2840-6-6. DOI: https://doi.org/10.1186/1475-2840-6-6
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