Sitagliptin protects liver against aflatoxin B1‐induced hepatotoxicity through upregulating Nrf2/ARE/HO‐1 pathway

Ji, Yujiang; Nyamagoud, Sanatkumar Bharamu; Sreeharsha, Nagaraja; Mishra, Anurag; Gubbiyappa, Shiva Kumar; Singh, Yogendra

doi:10.1002/biof.1573

Cited by 28 publications

(13 citation statements)

References 49 publications

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“…AFB 1 sharply downregulated approximately 70% abundances of these two proteins, which might promote AFB 1 -induced oxidative injury in the liver of broilers. These findings are similar to previous reports [39,40]. Intriguingly, dietary supplementation of HD at 500 and 1000 mg/kg mitigated AFB 1 -induced downregulation of NQO1 and HO1 proteins, which may be attributed to reduced oxidative injury in livers induced by AFB 1 .…”

Section: Discussionsupporting

confidence: 91%

Mitigation of Aflatoxin B1 Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks

Zhao

Deng

et al. 2021

Antioxidants

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The objective of this study was to explore the mechanism of Hedyotis diffusa (HD) in mediating the detoxification of aflatoxin B1 (AFB1)-induced hepatic injury in chicks. A total of 144 one-day-old male broilers (Cobb 500) were randomly assigned to four treatment groups (n = 6 cages/diet, 6 chicks/cage). After three days of acclimation, the broilers were fed either a control diet (Control), Control plus 0.5 mg/kg of AFB1, or Control plus 0.5 mg/kg AFB1 with 500 or 1000 mg/kg HD for two weeks. Both serum and liver were collected at the end of the feeding trial for biochemistry, histology, and NF-E2-related nuclear factor 2 (NRF2)/antioxidant response element (ARE) signaling analysis. Compared with Control, the AFB1 treatment caused liver injury and decreased (p < 0.05) body weight gain, feed intake, feed conversion ratio, and serum albumin and total protein by 6.2–20.7%. AFB1 also induced swelling, necrosis, and severe vacuolar degeneration in chicks’ livers. Notably, HD supplementation at 500 and 1000 mg/kg mitigated (p < 0.05) the alterations induced by AFB1. HD supplementation alleviated (p < 0.05) AFB1-induced impairment in hepatic glutathione peroxidase activity, protein carbonyl, and exo-AFB1-8,9-epoxide (AFBO)–DNA concentrations by 57.7–100% and increased (p < 0.05) the activities of superoxide dismutase and catalase by 23.1–40.9% more than those of AFB1 treatment alone. Furthermore, HD supplementation at the two doses upregulated (p < 0.05) NRF2, NAD(P)H: quinone oxidoreductase-1, heme oxygenase-1, glutathione cysteine ligase catalytic subunit, and glutathione-S transferase A2 and A3 in livers relative to the AFB1 group by 0.99–3.4-fold. Overall, dietary supplementation of HD at a high dose displayed better protection effects against aflatoxicosis. In conclusion, a dietary HD supplementation at 500 and 1000 mg/kg protected broilers from AFB1-induced hepatotoxicity, potentially due to the activation of NRF2/ARE signaling in the chicks.

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Section: Discussionsupporting

confidence: 91%

Mitigation of Aflatoxin B1 Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks

Zhao

Deng

et al. 2021

Antioxidants

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“…Furthermore, for rats, acute oral AFB1 (44–663 μg of AFB1 kg −1 of b. w.) led to liver damage, manifesting in inflammatory infiltrate, nuclear vacuolation and necrosis, in line with our results [ 30 ]. Similar results were reported for Cobb broilers, in which AFB1 induced histopathological lesions; grape seed proanthocyanidin extract (250 and 500 mg kg −1 ) + AFB1 (1 mg kg −1 ) mitigated AFB1’s negative effects in rats with sitagliptin activating the Nrf2-ARE-HO-1 signaling pathway to protect liver against AFB1-induced injury, while tea polyphenols protected hepatotoxicity against AFB1-induced injury in rats [ 29 , 30 , 31 ].…”

Section: Discussionsupporting

confidence: 77%

Dietary Curcumin Alleviated Aflatoxin B1-Induced Acute Liver Damage in Ducks by Regulating NLRP3–Caspase-1 Signaling Pathways

Jin

Yang

Wang

et al. 2021

Foods

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Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in animal feed and human food; it represents a serious threat to human and animal health. This study investigates the mechanism by which dietary curcumin protected liver against acute damage caused by AFB1 administration in ducks. One-day-old male ducks (n = 450) were randomly assigned to three groups, the control group, the AFB1 group, and the AFB1 + curcumin group; the first group were fed with basic diet, while the third group was fed basic diet containing 500 mg/kg curcumin. Ducks in the AFB1 group and AFB1 + curcumin group were challenged with AFB1 at the age of 70 days. The results show that AFB1 administration caused liver damage, increased CYP450 content and AFB1-DNA adducts in the liver, and induced oxidative stress and inflammatory response in the liver. Dietary curcumin significantly inhibited the generation of H2O2 and MDA in liver, activated the Nrf2-ARE signaling pathway, and suppressed the NLRP3–caspase-1 signaling pathway in the liver of ducks. Conclusively, curcumin in diet could protect duck liver against the generation of AFB1-DNA adducts, toxicity, oxidation stress and inflammatory response induced by AFB1 through regulating the NLRP3–caspase-1 signaling pathways, demonstrating that curcumin is a potential feed additive agent to reduce the serious harmful effects of AFB1 on duck breeding.

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“…The Keap1/Nrf2/ARE pathway regulates the expression of many antioxidant enzymes and phase II detoxifying enzymes, such as heme oxygenase-1 (HO-1), GR, glutathione peroxidase (GSH-Px), NAD(P)H dehydrogenase, quinone 1 (NQO1), GST, and SOD. AFs downregulated many antioxidants, including SOD, HO-1, NQO1, GSH-Px, catalase (CAT), GST, and GR, in many studies and experimental models (Yener et al, 2009;Alm-Eldeen et al, 2015;Yang et al, 2016;Vipin et al, 2017;Muhammad et al, 2018a;Muhammad et al, 2018b;Ji et al, 2020). However, one study found that AFs upregulated the expression of Nrf2 (Liu and Wang, 2016).…”

Section: The Dual Role Of Afs In the Regulation Of Autophagymentioning

confidence: 99%

Contamination of Aflatoxins Induces Severe Hepatotoxicity Through Multiple Mechanisms

et al. 2021

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Aflatoxins (AFs) are commonly contaminating mycotoxins in foods and medicinal materials. Since they were first discovered to cause “turkey X” disease in the United Kingdom in the early 1960s, the extreme toxicity of AFs in the human liver received serious attention. The liver is the major target organ where AFs are metabolized and converted into extremely toxic forms to engender hepatotoxicity. AFs influence mitochondrial respiratory function and destroy normal mitochondrial structure. AFs initiate damage to mitochondria and subsequent oxidative stress. AFs block cellular survival pathways, such as autophagy that eliminates impaired cellular structures and the antioxidant system that copes with oxidative stress, which may underlie their high toxicities. AFs induce cell death via intrinsic and extrinsic apoptosis pathways and influence the cell cycle and growth via microribonucleic acids (miRNAs). Furthermore, AFs induce the hepatic local inflammatory microenvironment to exacerbate hepatotoxicity via upregulation of NF-κB signaling pathway and inflammasome assembly in the presence of Kupffer cells (liver innate immunocytes). This review addresses the mechanisms of AFs-induced hepatotoxicity from various aspects and provides background knowledge to better understand AFs-related hepatoxic diseases.

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Sitagliptin protects liver against aflatoxin B1‐induced hepatotoxicity through upregulating Nrf2/ARE/HO‐1 pathway

Cited by 28 publications

References 49 publications

Mitigation of Aflatoxin B1 Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks

Mitigation of Aflatoxin B1 Hepatoxicity by Dietary Hedyotis diffusa Is Associated with Activation of NRF2/ARE Signaling in Chicks

Dietary Curcumin Alleviated Aflatoxin B1-Induced Acute Liver Damage in Ducks by Regulating NLRP3–Caspase-1 Signaling Pathways

Contamination of Aflatoxins Induces Severe Hepatotoxicity Through Multiple Mechanisms

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