Alteration of hepatocellular antioxidant gene expression pattern and biomarkers of oxidative damage in diazinon-induced acute toxicity in Wistar rat: a time–course mechanistic study

Hassani, Shokoufeh; Maqbool, Faheem; Maghsoudi, Armin Salek; Rahmani, Soheila; Shadboorestan, Amir; Nili‐Ahmadabadi, Amir; Amini, Mohsen; Norouzi, Parviz; Abdollahi, Mohammad

doi:10.17179/excli2017-760

Cited by 18 publications

(7 citation statements)

References 58 publications

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“…Organophosphates were demonstrated to increase NO production by increasing NO synthase activity [ 67 ]. Protein carbonyl (PC) is the most widely used marker of protein oxidation and the most universal signal for oxidative stress [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism

Nassar,

El-Kholy,

El-Sawi

et al. 2023

Toxics

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The health benefits of thymoquinone (TQ) have been a significant focus of numerous studies. However, more research is needed to ascertain whether its nano-form can effectively treat or prevent chronic diseases. In this study, we investigated how thymoquinone and its nanoparticles can mitigate liver damage induced by diazinon in male Wistar rats and explored the intracellular mechanisms involved. Forty-two Wistar male rats (n = 42) were randomly allotted into seven groups. Group 1 served as the control. Group 2 (vehicle) consisted of rats that received corn oil via a gastric tube daily. In Group 3 (TQ), rats were given a daily oral administration of TQ (40 mg/kg bw). Group 4 (thymoquinone nanoparticles, NTQ) included rats that received NTQ (0.5 mg/kg bw) orally for 21 days. Group 5 (DZN) involved rats that were administered diazinon (DZN, 15 mg/kg bw) orally. In Group 6 (TQ + DZN), rats first received TQ orally, followed by DZN. Group 7 (NTQ + DZN) consisted of rats receiving NTQ orally, then DZN. After 21 days of treatment, the rats were euthanized. After oral administration of DZN, liver enzymes were significantly elevated (p < 0.05). Additionally, there were noticeable increases in oxidative injury markers, such as nitric oxide, malondialdehyde, redox oxygen radicals, and overall increases in hydrogen peroxide and liver protein carbonyl concentrations. This was accompanied by the upregulation of apoptotic markers (Bax, caspase9, caspase 3, bax/Bcl2 ratio), inflammatory cytokines (TNF-α, IL-6), and DNA damage. There was also a noteworthy decrease (p < 0.05) in the activities of antioxidant enzymes and anti-apoptotic markers. However, the oral administration of thymoquinone or its nanoparticle form mitigated these diazinon complications; our histopathological findings corroborated our biochemical and molecular observations. In conclusion, the significant antioxidant properties of thymoquinone, or its nanoparticle form, in tandem with the downregulation of apoptotic markers and inflammatory cytokines, provided a protective effect against hepatic dysfunction caused by diazinon.

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Section: Discussionmentioning

confidence: 99%

Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism

Nassar,

El-Kholy,

El-Sawi

et al. 2023

Toxics

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“…In a physiological state, free radicals, as products of cell physiological processes, are maintained at equilibrium by antioxidant system activity ( 46 ). While in pathological conditions, accumulating large amounts of free radicals can exceed the antioxidant defense capacity, leading to oxidative stress ( 47 , 48 ). A large body of evidence has demonstrated that an increased amount of ROS and weakened antioxidant defense caused by hyperglycemia result in oxidative stress causing damage to various cell macromolecules such as proteins, lipids, and nucleic acids ( 8 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

A systematic review on the role of melatonin and its mechanisms on diabetes-related reproductive impairment in non-clinical studies

Armandeh

Bameri²,

Haghi‐Aminjan³

et al. 2022

Front. Endocrinol.

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BackgroundDiabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin’s effect on the reproductive system adversely affected by diabetes mellitus (DM).MethodsA comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria.ResultsThe results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis.ConclusionMelatonin exerted a protective action on the impaired reproductive system in in-vivo and in-vitro models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.

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“…Sample cleaning was performed using an SPE column, C18/17%, 3 mL/200 mg. Chromatography was conducted on a 4.6 × 150 mm, 5 μm ZORBAX C18 column (Agilent, Germany). The protocol was set up in our lab in accordance with previous studies. , …”

Section: Methodsmentioning

confidence: 99%

“…The protocol was set up in our lab in accordance with previous studies. 26,27 RNA Extraction. Total RNA of islets in control and BPA-exposed groups was extracted using the Qiagen RNeasy mini kit according to the manufacturer's protocol.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Gene–Environmental Interplay in Bisphenol A Subchronic Animal Exposure: New Insights into the Epigenetic Regulation of Pancreatic Islets

Rahmani

Vakhshiteh

Hodjat

et al. 2020

Chem. Res. Toxicol.

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Endocrine-disrupting chemicals (EDCs) such as bisphenol A (BPA), which is widely used in the plastic industry, have recently been considered to be involved in the pathogenesis of metabolic disorders, including obesity and diabetes. The present study aimed to examine the potentially detrimental effects of BPA on glucose and energy metabolism at the epigenetic level. The blood glucose profile of Wistar rats receiving different oral doses of BPA over 28 days was assessed. At the end of the treatment, the islets of Langerhans were isolated and purified, and their RNA content was extracted. MicroRNA (miRNA) profiling was evaluated using the next generation sequencing (NGS) method. After performing bioinformatic analysis of the NGS data, the gene ontology and data enrichment in terms of significantly disturbed miRNAs were evaluated through different databases, including Enrichr and DIANA tools. Additionally, the DNA methylation and the level of expression of two critical genes in glucose metabolism (PPARγ, Pdx1) were assessed. Subchronic BPA exposure (406 mg/kg/day) disturbed the blood glucose profile (fasting blood glucose and oral glucose tolerance) of Wistar rats and resulted in considerable cytotoxicity. NGS data analyses revealed that the expression of some crucial miRNAs involved in β-cell metabolism and diabetes occurrence and development, including miR-375, miR-676, miR-126-a, and miR-340-5p, was significantly disrupted. According to the DNA methylation evaluation, both PPARγ and Pdx1 genes underwent changes in the methylation level at particular loci on the gene's promoter. The expression levels of these genes were upregulated and downregulated, respectively. Overall, subchronic BPA exposure could cause epigenetic dysregulation at the gene level and interfere with the expression of key miRNAs and the methylation process of genes involved in glucose homeostasis. Understanding the exact underlying mechanisms by which BPA and other EDCs induce endocrine disturbance could be of great importance in the way of finding new preventive and therapeutic approaches.

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Alteration of hepatocellular antioxidant gene expression pattern and biomarkers of oxidative damage in diazinon-induced acute toxicity in Wistar rat: a time–course mechanistic study

Cited by 18 publications

References 58 publications

Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism

Ameliorative Effect of Thymoquinone and Thymoquinone Nanoparticles against Diazinon-Induced Hepatic Injury in Rats: A Possible Protection Mechanism

A systematic review on the role of melatonin and its mechanisms on diabetes-related reproductive impairment in non-clinical studies

Gene–Environmental Interplay in Bisphenol A Subchronic Animal Exposure: New Insights into the Epigenetic Regulation of Pancreatic Islets

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