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

Ling Zhao; Jiang Deng; Zi-Jian Xu; Wan-Po Zhang; Mahmoud Mohamed Khalil; Niel Alexander Karrow; Lv-Hui Sun

doi:10.3390/antiox10060878

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

Antioxidants (Basel). 2021 May 30;10(6):878. doi: 10.3390/antiox10060878.

Authors

Ling Zhao¹, Jiang Deng¹, Zi-Jian Xu¹, Wan-Po Zhang², Mahmoud Mohamed Khalil³, Niel Alexander Karrow⁴, Lv-Hui Sun¹

Affiliations

¹ Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
² Department of Veterinary Pathology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
³ Animal Production Department, Faculty of Agriculture, Benha University, Cairo 13736, Egypt.
⁴ Department of Animal Biosciences, University of Guelph, Guelph, ON N1G2W1, Canada.

Abstract

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.

Keywords: Hedyotis diffusa; NRF2/ARE signaling; aflatoxin B1; broilers; hepatotoxicity.

Abstract

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