Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver

Miranda, Camila Araújo; Guimarães, Anilda Rufino de Jesus Santos; Bizerra, Paulo Francisco Veiga; Mingatto, Fábio Ermínio

doi:10.1080/15287394.2020.1805078

Cited by 11 publications

(5 citation statements)

References 71 publications

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“…Diazinon is a broad-spectrum insecticide extensively used to control pests in crops and animals ( Figure 5 D). Studies have shown that diazinon produces tissue toxicity, especially to the liver [ 30 , 31 ]. In addition, diazinon not only induces an increase in ROS [ 32 , 33 ], but also causes metabolic disturbance [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

et al. 2022

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Tyrosine is an essential ketogenic and glycogenic amino acid for the human body, which means that tyrosine is not only involved in protein metabolism, but also participates in the metabolism of lipids and carbohydrates. The liver is an important place for metabolism of lipids, carbohydrates, and proteins. The metabolic process of biological macro-molecules is a basis for maintaining the physiological activities of organisms, but the cross-linking mechanism of these processes is still unclear. Here, we found that the tyrosine-metabolizing enzymes, which were specifically and highly expressed in the liver, were significantly down-regulated in hepatocellular carcinoma (HCC), and had a correlation with a poor prognosis of HCC patients. Further analysis found that the reduction of tyrosine metabolism would activate the cell cycle and promote cell proliferation. In addition, we also found that the solute carrier family 27 member 5 (SLC27A5) regulates the expression of tyrosine-metabolizing enzymes through nuclear factor erythroid 2-related factor 2 (NRF2). Therefore, the SLC27A5 and tyrosine-metabolizing enzymes that we have identified coordinate lipid and tyrosine metabolism, regulate the cell cycle, and are potential targets for cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

et al. 2022

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“…Similar pathways linking environmental pollution with NAFLD in terms of both epidemiologic findings of increased NAFLD risk and animal/in vitro evidence of mitochondrial dysfunction also have been shown in the case of air pollution [ 127 , 128 , 129 ], endocrine disrupting chemicals [ 127 , 128 , 129 , 130 , 131 ], and pesticides [ 132 , 133 , 134 , 135 ].…”

Section: Mitochondrial Dysfunction In the Livermentioning

confidence: 56%

Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests

Ciaula

Calamita

Shanmugam

et al. 2021

IJMS

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The liver plays a key role in systemic metabolic processes, which include detoxification, synthesis, storage, and export of carbohydrates, lipids, and proteins. The raising trends of obesity and metabolic disorders worldwide is often associated with the nonalcoholic fatty liver disease (NAFLD), which has become the most frequent type of chronic liver disorder with risk of progression to cirrhosis and hepatocellular carcinoma. Liver mitochondria play a key role in degrading the pathways of carbohydrates, proteins, lipids, and xenobiotics, and to provide energy for the body cells. The morphological and functional integrity of mitochondria guarantee the proper functioning of β-oxidation of free fatty acids and of the tricarboxylic acid cycle. Evaluation of the liver in clinical medicine needs to be accurate in NAFLD patients and includes history, physical exam, imaging, and laboratory assays. Evaluation of mitochondrial function in chronic liver disease and NAFLD is now possible by novel diagnostic tools. “Dynamic” liver function tests include the breath test (BT) based on the use of substrates marked with the non-radioactive, naturally occurring stable isotope 13C. Hepatocellular metabolization of the substrate will generate 13CO2, which is excreted in breath and measured by mass spectrometry or infrared spectroscopy. Breath levels of 13CO2 are biomarkers of specific metabolic processes occurring in the hepatocyte cytosol, microsomes, and mitochondria. 13C-BTs explore distinct chronic liver diseases including simple liver steatosis, non-alcoholic steatohepatitis, liver fibrosis, cirrhosis, hepatocellular carcinoma, drug, and alcohol effects. In NAFLD, 13C-BT use substrates such as α-ketoisocaproic acid, methionine, and octanoic acid to assess mitochondrial oxidation capacity which can be impaired at an early stage of disease. 13C-BTs represent an indirect, cost-effective, and easy method to evaluate dynamic liver function. Further applications are expected in clinical medicine. In this review, we discuss the involvement of liver mitochondria in the progression of NAFLD, together with the role of 13C-BT in assessing mitochondrial function and its potential use in the prevention and management of NAFLD.

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“…The effects of DZN on mitochondria have been previously reported (Ogutcu et al, 2006). It damages the mitochondrial membrane (Miranda et al, 2020), causes vacuolation and swelling in rat liver and heart mitochondria (Ogutcu et al, 2006). Also, it disables p450 cytochromes and microsomes in the human liver and causes changes in the liver enzymes (Ogutcu et al, 2006).…”

Section: Discussionmentioning

confidence: 94%

Diazinon exposure reduces bone mineral density in adult and immature rats: A histomorphometric and radiographic study

et al. 2021

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Diazinon has been widely used as a domestic and agricultural pesticide. This study examined the effects of diazinon on bone mineral density (BMD) of mature and immature rats. For this purpose, 24 adult Wistar rats (male; 8 weeks old) were initially divided into four groups ( n = 6). Corn oil was used as the control while diazinon at 15, 30, and 45 mg/kg in corn oil was given to mature rats via gavage per day. Since these dosages were lethal for the immature rats, 12 immature Wistar rats (male; 4 weeks old) ( n = 6) were gavaged with corn oil as control and 5 mg/kg of diazinon in corn oil. The animals were sacrificed on day 28 with their left femur bones removed for histomorphometric studies. BMD was measured in the right femur, using standardized radiographs in the femoral head, femoral neck, greater trochanter, and shaft. The Image J Program was used for measuring the bone lamellae and epiphyseal growth plates. The results of this study for the first time revealed that diazinon reduced BMD in both adults and immature rats. Diazinon exposure was associated with diminished trabecular and cortical bone density. Correspondingly, our results indicated that in immature rats, DZN led to the reduction in the epiphyseal growth plate width, both in the proliferation and hypertrophic zones. These results suggested that diazinon might be associated with impaired bone longitudinal growth as well as bone metabolism in adults.

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Diazinon impairs bioenergetics and induces membrane permeability transition on mitochondria isolated from rat liver

Cited by 11 publications

References 71 publications

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

Mitochondria Matter: Systemic Aspects of Nonalcoholic Fatty Liver Disease (NAFLD) and Diagnostic Assessment of Liver Function by Stable Isotope Dynamic Breath Tests

Diazinon exposure reduces bone mineral density in adult and immature rats: A histomorphometric and radiographic study

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