Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

Xu, Mingyuan; Wang, Pan; Sun, Ying-Jian; Wu, Yi‐Jun

doi:10.1016/j.tox.2017.04.008

Cited by 45 publications

(31 citation statements)

References 44 publications

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“…Another finding parallel to this damage is a decrease in the body weight of animals and a significant increase in liver weight and liver weight/body weight ratio. Comparing current studies with previous studies on cadmium exposure; oxidative stress parameters (Abarikwu, Njoku, Lawrence, Charles, & Ikewuchi, ; Dkhil et al, ; Eşrefoglu et al, ; Jurczuk et al, ; Karaca and Eraslan, ; Koyu et al, ; Layachi and Kechrid, ; Xu et al, ; Zhang et al, ), some biochemical parameters (Abarikwu et al, ; Layachi & Kechrid, ; Pari & Murugavel, ; Pari & Shagirtha, ; Zhang et al, ), liver histopathology (Andjelkovic et al, ; Koyu et al, ; Olisekodiaka, Igbeneghu, Onuegbu, Oduru, & Lawal, ; Xu et al, ) and, in terms of body weight and liver weight (Layachi & Kechrid, ) have similarities.…”

Section: Discussionsupporting

confidence: 62%

“…There are many studies shown that negative effects of cadmium on the liver (Andjelkovic et al, 2019;Jurczuk, Brzóska, Moniuszko-Jakoniuk, Gałazyn-Sidorczuk, & Kulikowska-Karpińska, 2004;Karaca & Eraslan, 2013;Koyu, Gokcimen, Ozguner, Bayram, & Kocak, 2006;Xu, Wang, Sun, & Wu, 2017;Zhu et al, 2019). In the treatment of these heavy metal-related intoxications, the use of a chelator for the chelation of the metals passing into the systemic circulation is often preferred (Flora, Mittal, & Mehta, 2008;Tandon et al, 2003;Xu et al, 1996).…”

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confidence: 99%

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The effect of diosmin against liver damage caused by cadmium in rats

Ağır

Eraslan

2019

J Food Biochem

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A total of 40, male Wistar Albino, 2–3‐months‐old rats were used and divided into four groups. Control group received the vehicle alone, diosmin group received 100 mg/kg.bw diosmin, the cadmium group received 200 ppm cadmium, cadmium plus diosmin group received 200 ppm cadmium, and 100 mg/kg.bw diosmin for 30 days. Some biochemical parameters (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase) and oxidative stress parameters (malondialdehyde [MDA], nitric oxide [NO], superoxide dismutase [SOD], catalase [CAT], gluthatione peroxidase [GSH‐Px], and glutathione [GSH]) were analyzed in the samples. Histo‐pathological findings were evaluated in the liver. The body weights and liver weights of the animals were measured. The MDA and NO levels and biochemical enzyme activities examined were increased, whereas SOD, CAT, and GSH‐Px activities and GSH levels decreased in cadmium‐exposed group. There were also negative changes in body weight, liver weight, and liver tissue histo‐phathology. Positive improvements were observed in all these parameters evaluated of the group co‐administered cadmium and diosmin. Practical applications Cadmium is one of the common environmental pollutants. Diosmin is a type of flavonoid found mainly in citrus fruits. It can also be produced from hesperidine. This compound is used for medical purposes and also has strong antioxidant properties. One of the toxic effects mechanisms of cadmium is oxidative stress and causes liver damage with different pathways. This compound can be used as a supporting agent in addition to the main treatment options against liver damage in case of exposure to possible cadmium. This flavonoid can also be taken with food for prophylactic purposes.

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Section: Discussionsupporting

confidence: 62%

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confidence: 99%

The effect of diosmin against liver damage caused by cadmium in rats

Ağır

Eraslan

2019

J Food Biochem

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“…As the technology advances, new methodologies such as omics approaches are developed, and great progress has been made in the study of mixture toxicology, which increases our ability to predict the potential risks of exposure to mixtures 12 .The acute toxicity of CPF and Cd are well understood 13,14 . We have reported that chronic exposure to CPF and Cd individually and in combination caused neurotoxicity and hepatotoxicity 15,16 . We found that CPF and Cd disturbed energy and amino acids metabolism in the brain and liver.…”

mentioning

confidence: 99%

“…The acute toxicity of CPF and Cd are well understood 13,14 . We have reported that chronic exposure to CPF and Cd individually and in combination caused neurotoxicity and hepatotoxicity 15,16 . We found that CPF and Cd disturbed energy and amino acids metabolism in the brain and liver.…”

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confidence: 99%

Identification of metabolite biomarkers in serum of rats exposed to chlorpyrifos and cadmium

Wang

Sun

et al. 2020

Sci Rep

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Chlorpyrifos (CPF) and cadmium (Cd) are widespread environmental pollutants, which are often present in drinking water and foods. However, the combined effects of CPF and Cd were not entirely clear at present. There was also no biomarker available to diagnose the poisoning of the two chemicals at low dose for long-term exposures. In this study, we investigated the change of serum metabolites of rats with subchronic exposure to CPF, Cd, and CPF plus Cd using gas chromatography-mass spectrometerbased metabolomics approach. We performed a stepwise optimization algorithm based on receiver operating characteristic to identify serum metabolite biomarkers for toxic diagnosis of the chemicals at different doses after 90-day exposure. We found that aminomalonic acid was the biomarker for the toxicity of Cd alone administration, and serine and propanoic acid were unique biomarkers for the toxicities of CPF plus Cd administrations. Our results suggest that subchronic exposure to CPF and Cd alone, or in combination at their low doses, could cause disturbance of energy and amino acid metabolism. Overall, we have shown that analysis of serum metabolomics can make exceptional contributions to the understanding of the toxic effects following long-term low-dose exposure of the organophosphorus pesticide and heavy metal.Chlorpyrifos (CPF) is a widely used organophosphorus insecticide with cholinergic toxicity 1,2 . CPF exposure can induce severe toxicity in multiple organs 3 . Cadmium (Cd) is a persistent toxic metal with very long half-life 4 . Chronic Cd exposure induces toxicity in kidneys, liver, and bones 5-8 . Due to their toxicity to different target organs, CPF and Cd pose significant threats to public health.CPF and Cd are widespread environmental toxicants which often coexist in water, air, and soil 3,9 . Given that environmental toxicants are widespread, organisms are seldom exposed to only one chemical. Thus, it is important to study the combined toxicity of multiple toxicants. More and more studies suggest that combined exposure to different chemicals can potentiate the toxicity of single chemical alone 2,10,11 . As the technology advances, new methodologies such as omics approaches are developed, and great progress has been made in the study of mixture toxicology, which increases our ability to predict the potential risks of exposure to mixtures 12 .The acute toxicity of CPF and Cd are well understood 13,14 . We have reported that chronic exposure to CPF and Cd individually and in combination caused neurotoxicity and hepatotoxicity 15,16 . We found that CPF and Cd disturbed energy and amino acids metabolism in the brain and liver. Therefore, in this study, we try to identify the biomarkers in serum, upon exposure to CPF, Cd, and their mixture.Metabolomics is a very useful approach for toxicological studies because it can characterize the changes of metabolite levels induced by toxic chemicals and identify the specific biomarkers for each toxicant 17,18 . In the present study, we aim to use metabolomics analysis in se...

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“…Recently, metabolomic studies on cadmium exposures demonstrated synergistic effects on pesticide-related hepatotoxicity. In developing countries, the use of pesticides and insecticides to increase crop productivity is burgeoning and concomitant use of Ayurveda drugs such as Bhasma could potentiate accelerated liver injury 17. Most of the heavy metal concentrations in the Bhasma were beyond permissible and tolerable levels.…”

Section: Discussionmentioning

confidence: 99%

Ayurveda metallic-mineral ‘Bhasma’-associated severe liver injury

Philips¹,

Paramaguru

Augustine

2018

BMJ Case Reports

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Ayurveda Bhasma is a metallic-mineral preparation homogenised with herbal juices or decoctions and modified with heat treatment to apparently detoxify the heavy metals. It is widely recommended for the treatment of many disease conditions by practitioners of complementary and alternative medicine in the absence of good quality clinical trial evidence on its safety and efficacy. Heavy metal-induced liver injury is widely reported in the literature, and heavy metal adulteration of non-Bhasma-related Ayurveda and herbal products has been well described. We report a patient who developed severe liver injury requiring listing for liver transplantation for improved survival, after consumption of Bhasma for dyspepsia. This case describes the first documented case and toxicology analysis of Ayurveda Bhasma associated with severe drug-induced liver injury. Physicians must be alert regarding patient's use of supposedly safe Ayurveda Bhasma that may promote acute severe liver injury in the absence of other known aetiologies.

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Metabolomic analysis for combined hepatotoxicity of chlorpyrifos and cadmium in rats

Cited by 45 publications

References 44 publications

The effect of diosmin against liver damage caused by cadmium in rats

The effect of diosmin against liver damage caused by cadmium in rats

Identification of metabolite biomarkers in serum of rats exposed to chlorpyrifos and cadmium

Ayurveda metallic-mineral ‘Bhasma’-associated severe liver injury

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