Prenatal ethanol exposure induces dynamic changes of expression and activity of hepatic cytochrome P450 isoforms in male rat offspring

Sun, Xian-He; Li, He; Bi, Huichang; Huang, Min; Xiang, E; Li, Xia; Wang, Hui; Guo, Yu

doi:10.1016/j.reprotox.2022.03.002

Cited by 3 publications

(2 citation statements)

References 55 publications

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“…Individually housed pregnant rats were kept in the aforementioned typical lab settings. 13 Animals and experimental design. One week after delivery, pups were randomized to 4 groups (8 rats per each), and maternal rats were rotated daily between cages for feeding and to eliminate maternal effects among groups.…”

Section: Animals and Experimental Designmentioning

confidence: 99%

The IL-6/HO-1/STAT3 signaling pathway is implicated in the amelioration of acetaminophen-induced hepatic toxicity: A neonatal rat model

et al. 2023

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The widespread use of acetaminophen (APAP) in children as an over-the-counter treatment can cause acute liver failure through accidental overdose or ingestion. Therefore, the current research sought to investigate the function of hemin in mitigating the acute hepatotoxic effect of APAP in rat offspring. Thirty-two rats were assigned into four groups: control, hemin, APAP, and hemin/APAP groups. Liver enzymes were measured in serum along with oxidative stress indicators, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), total nitrites (NOx), and caspase 3 in liver. Immunoblotting of heme oxygenase-1 (HO-1), interleukin-6 (IL-6), Janus kinase 2 (Jak2), and signal transducer and activator of transcription 3 (STAT3) was carried out. The Bax/Bcl2 mRNA expression ratio was determined. A histological study and an immunohistochemical study of phosphorylated STAT3 were also done. Hemin reduced liver enzymes, MDA, TNF-α, NOx, caspase 3, IL-1β, p-STAT3 expression, p-Jak2 expression, IL-6 expression, and Bax/Bcl2 mRNA expression ratio. In contrast, hemin increased GSH, TAC, and the expression of HO-1, improving the histopathological picture of liver tissue. Thus, hemin could ameliorate APAP-induced hepatic toxicity in rat offspring through anti-oxidant, anti-apoptotic, and anti-inflammatory actions with a possible role for the IL-6/HO-1/Jak2/STAT3 pathway.

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Section: Animals and Experimental Designmentioning

confidence: 99%

The IL-6/HO-1/STAT3 signaling pathway is implicated in the amelioration of acetaminophen-induced hepatic toxicity: A neonatal rat model

et al. 2023

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“…In addition, while several drugs inhibit CYP2E1 activity in vitro, some compounds and various disease states show opposite effects in humans and upregulate enzymatic activity. Recently, Sun et al utilized aniline as a probe to compare hepatic CYP2E1 activity and found that prenatal ethanol exposure (4 g/kg/day) in male rat offspring inhibits CYP2E1 and 2D1 activities [ 107 ]. Additionally, a cocktail probe method was employed to examine the effects of Aidi (ADI) injection (a traditional Chinese medicine used for chemotherapy for various tumors) on various CYP activities in normal and liver cancer rats [ 108 ].…”

Section: Cyp2e1 In Clinical Drug-drug and Alcohol-drug Interactionsmentioning

confidence: 99%

Hepatic, Extrahepatic and Extracellular Vesicle Cytochrome P450 2E1 in Alcohol and Acetaminophen-Mediated Adverse Interactions and Potential Treatment Options

Kumar

Singla

Singh

et al. 2022

Cells

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Alcohol and several therapeutic drugs, including acetaminophen, are metabolized by cytochrome P450 2E1 (CYP2E1) into toxic compounds. At low levels, these compounds are not detrimental, but higher sustained levels of these compounds can lead to life-long problems such as cytotoxicity, organ damage, and cancer. Furthermore, CYP2E1 can facilitate or enhance the effects of alcohol-drug and drug-drug interactions. In this review, we discuss the role of CYP2E1 in the metabolism of alcohol and drugs (with emphasis on acetaminophen), mediating injury/toxicities, and drug-drug/alcohol-drug interactions. Next, we discuss various compounds and various nutraceuticals that can reduce or prevent alcohol/drug-induced toxicity. Additionally, we highlight experimental outcomes of alcohol/drug-induced toxicity and potential treatment strategies. Finally, we cover the role and implications of extracellular vesicles (EVs) containing CYP2E1 in hepatic and extrahepatic cells and provide perspectives on the clinical relevance of EVs containing CYP2E1 in intracellular and intercellular communications leading to drug-drug and alcohol-drug interactions. Furthermore, we provide our perspectives on CYP2E1 as a druggable target using nutraceuticals and the use of EVs for targeted drug delivery in extrahepatic and hepatic cells, especially to treat cellular toxicity.

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Prenatal ethanol exposure and changes in fetal neuroendocrine metabolic programming

Liu,

Wen,

et al. 2023

Biol Res

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Prenatal ethanol exposure (PEE) (mainly through maternal alcohol consumption) has become widespread. However, studies suggest that it can cause intrauterine growth retardation (IUGR) and multi-organ developmental toxicity in offspring, and susceptibility to various chronic diseases (such as neuropsychiatric diseases, metabolic syndrome, and related diseases) in adults. Through ethanol’s direct effects and its indirect effects mediated by maternal-derived glucocorticoids, PEE alters epigenetic modifications and organ developmental programming during fetal development, which damages the offspring health and increases susceptibility to various chronic diseases after birth. Ethanol directly leads to the developmental toxicity of multiple tissues and organs in many ways. Regarding maternal-derived glucocorticoid-mediated IUGR, developmental programming, and susceptibility to multiple conditions after birth, ethanol induces programmed changes in the neuroendocrine axes of offspring, such as the hypothalamus-pituitary-adrenal (HPA) and glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axes. In addition, the differences in ethanol metabolic enzymes, placental glucocorticoid barrier function, and the sensitivity to glucocorticoids in various tissues and organs mediate the severity and sex differences in the developmental toxicity of ethanol exposure during pregnancy. Offspring exposed to ethanol during pregnancy have a “thrifty phenotype” in the fetal period, and show “catch-up growth” in the case of abundant nutrition after birth; when encountering adverse environments, these offspring are more likely to develop diseases. Here, we review the developmental toxicity, functional alterations in multiple organs, and neuroendocrine metabolic programming mechanisms induced by PEE based on our research and that of other investigators. This should provide new perspectives for the effective prevention and treatment of ethanol developmental toxicity and the early prevention of related fetal-originated diseases.

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Prenatal ethanol exposure induces dynamic changes of expression and activity of hepatic cytochrome P450 isoforms in male rat offspring

Cited by 3 publications

References 55 publications

The IL-6/HO-1/STAT3 signaling pathway is implicated in the amelioration of acetaminophen-induced hepatic toxicity: A neonatal rat model

The IL-6/HO-1/STAT3 signaling pathway is implicated in the amelioration of acetaminophen-induced hepatic toxicity: A neonatal rat model

Hepatic, Extrahepatic and Extracellular Vesicle Cytochrome P450 2E1 in Alcohol and Acetaminophen-Mediated Adverse Interactions and Potential Treatment Options

Prenatal ethanol exposure and changes in fetal neuroendocrine metabolic programming

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