Betaine protects mice against acetaminophen hepatotoxicity possibly via mitochondrial complex II and glutathione availability

Khodayar, Mohammad Javad; Kalantari‬, Heibatullah; Khorsandi, Layasadat; Rashno, Mohammad; Zeidooni, Leila

doi:10.1016/j.biopha.2018.04.154

Cited by 31 publications

(19 citation statements)

References 51 publications

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“…The activity of ALT and AST enzymes is one of the most sensitive biomarkers to detect liver damage. 3 Based on the findings of this study, the single dose of APAP (300 mg/kg) increased the serum AST and ALT levels. This increase is due to the release of these enzymes from the cytoplasm of the damaged cells to the bloodstream, indicating hepatocyte necrosis or hepatic inflammation.…”

Section: Discussionmentioning

confidence: 70%

“…18,33 The Nrf2 induces cytoprotective enzymes in oxidative stress conditions. 3 Among these genes, HO-1 Figure 5. Results of Western blot of Nrf2 in the control and therapeutic groups.…”

Section: Discussionmentioning

confidence: 99%

“…The doses of betaine and APAP were chosen based on our previous study. 3,20 Twenty-four hours after administration of APAP, all mice were anesthetized and blood samples were collected from heart. Blood samples then at 3000 for 10 min were centrifuged and serum separated.…”

Section: Experimental Designmentioning

confidence: 99%

“…2 In our previous study, mice pretreated with 125, 250, 500, and 1000 mg/kg betaine and the dose of 500 mg/kg was selected as the effective dose against hepatotoxicity induced by APAP. 3 So, in this study, complementary tests were performed at a dose of 500 mg/kg to evaluate APAP hepatotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine

et al. 2020

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Overdose of acetaminophen (APAP) is the main reason for acute liver failure. Oxidative stress is associated with hepatotoxicity caused by APAP. Betaine is a methyl donor and S-adenosylmethionine precursor. The present study investigated the effect of betaine and the role of nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes in hepatotoxicity induced by APAP in mice. In this study, male Naval Medical Research Institute (NMRI) mice were treated with 500 mg/kg of betaine for 5 days followed with a single dose of APAP 300 mg/kg on the fifth day. Biochemical, histological, immunohistochemical, Western blot, and real-time polymerase chain reaction (PCR) analyses were then conducted. The results of the present study showed that betaine pretreatment improved hepatotoxicity through the reduction of serum ALT and AST levels and ameliorating histopathological finding. Betaine pretreatment also increased glutathione level and decreased malondialdehyde level. Importantly, the results of immunohistochemical, Western blot and real-time PCR showed that the APAP increased the expression of the genes and proteins of Nrf2 and HO-1. While betaine decreased Nrf2 and HO-1 expression in comparison with the APAP group. The findings of this study demonstrated that the increased expression of Nrf2 and HO-1 genes and proteins by APAP is a compensatory mechanism to combat acute liver toxicity. While the protective effect of betaine against acute liver injury induced by APAP is independent on the Nrf2 and HO-1 genes but occurs via modifying cysteine supply as a precursor of glutathione in the transsulfuration pathway in the liver.

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Section: Discussionmentioning

confidence: 70%

“…18,33 The Nrf2 induces cytoprotective enzymes in oxidative stress conditions. 3 Among these genes, HO-1 Figure 5. Results of Western blot of Nrf2 in the control and therapeutic groups.…”

Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine

et al. 2020

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“…APAP undergoes conversion to a toxic metabolite NAPQI by cytochrome P450, which leads to NAPQI-GSH formation, the rapid depletion of liver GSH, and the excessive formation of mitochondrial ROS (Antoine, Williams, & Park, 2008;Khodayar, Kalantari, Khorsandi, Rashno, & Zeidooni, 2018). APAP undergoes conversion to a toxic metabolite NAPQI by cytochrome P450, which leads to NAPQI-GSH formation, the rapid depletion of liver GSH, and the excessive formation of mitochondrial ROS (Antoine, Williams, & Park, 2008;Khodayar, Kalantari, Khorsandi, Rashno, & Zeidooni, 2018).…”

Section: Discussionmentioning

confidence: 99%

Silkworm pupa oil attenuates acetaminophen‐induced acute liver injury by inhibiting oxidative stress‐mediated NF‐κB signaling

Long

Song

Zhao

et al. 2019

Food Science & Nutrition

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Acetaminophen (APAP) overdose causes severe hepatotoxicity and acute liver failure. The current study aims to investigate the protection effects of silkworm pupa oil (SPO) against acute hepatic injury in APAP‐exposed Kunming mice. Our results showed that the liver index and the levels of serum alanine transaminase (ALT) and aspartate transaminase (AST) in mice subjected to APAP treatment were decreased by SPO. Supplement of SPO also restored hepatic histopathological alterations induced by APAP. The APAP‐induced increase in proinflammatory cytokines, including TNF‐α, IL‐6, and IL‐12, was reversed by SPO, which was mediated by the reduction of nuclear factor (NF)‐κB p65 expression and the increase in the expression of IκB‐α in liver tissue. Moreover, SPO inhibited APAP‐triggered oxidative stress by decreasing MDA level and increasing the activities of SOD and GSH‐Px. Collectively, SPO attenuated hepatic injury induced by APAP, which attributed to the suppression of oxidative stress‐mediated NF‐κB signaling. Our findings suggest that SPO supplementation may be potential strategy against acute hepatic injury.

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Cucumeropsis mannii seed oil protects against Bisphenol A‐induced testicular mitochondrial damages

Aja

Ogwoni

Agu

et al. 2023

Food Science & Nutrition

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There has been increasing search for the ameliorative properties of seed oils against toxicants. bisphenol A acts as an estrogenic endocrine‐disrupting chemical capable of causing male infertility. This study aimed to explore Cucumeropsis mannii seed oil effects against mitochondrial damage in rats using bisphenol A. Forty‐eight rats were randomly assigned to six groups (n = 6) of eight rats each and fed the same food and water for 6 weeks. The group A rats were given 1 mL olive oil, while the ones in group B were given bisphenol A at 100 mL/kg body weight via oral route. Group C received C. mannii seed oil 7.5 mL/kg body weight C. mannii seed oil, while group D, group E, and group F were pre‐administered bisphenol A at 100 mL/kg body weight, followed by treatment with C. mannii seed oil at 7.5, 5, and 2.5 mL/kg body weight, respectively. Antioxidant enzymes, glutathione, reactive oxygen species, testicular volume, malondialdehyde, body weight, and testicular studies were done using standard methods. The results of the bisphenol A‐administered group showed a significant decrease in the antioxidant enzymes, glutathione, body weight, and testicular volume with elevation in the levels of reactive oxygen species, malondialdehyde, and testicular indices. BPA + CMSO‐treated group showed a significant increase in GPx activity compared with BPA‐exposed rats. CMSO treatment significantly increased catalase activity in comparison with that of rats exposed to BPA. Remarkably, C. mannii seed oil and bisphenol A co‐administration significantly reversed the abnormalities observed in the dysregulated biochemical biomarkers. Our findings suggest that C. mannii seed oil has considerable antioxidant potential which can be explored in therapeutic development against systemic toxicity induced by exposure to bisphenol A. Cucumeropsis mannii seed oil protects against bisphenol A‐induced testicular mitochondria damages.

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Betaine protects mice against acetaminophen hepatotoxicity possibly via mitochondrial complex II and glutathione availability

Cited by 31 publications

References 51 publications

Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine

Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine

Silkworm pupa oil attenuates acetaminophen‐induced acute liver injury by inhibiting oxidative stress‐mediated NF‐κB signaling

Cucumeropsis mannii seed oil protects against Bisphenol A‐induced testicular mitochondrial damages

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