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Protective Effects of Crocetin on Arsenic Trioxide-Induced Hepatic Injury: Involvement of Suppression in Oxidative Stress and Inflammation Through Activation of Nrf2 Signaling Pathway in Rats.
Drug Des Devel Ther. 2020; 14:1921-1931.DD

Abstract

Purpose

Arsenic trioxide (ATO) has been shown to induce hepatic injury. Crocetin is a primary constituent of saffron, which has been verified to have antioxidant and anti-inflammatory effects. In the current experiment, we evaluated the efficacy of crocetin against ATO-induced hepatic injury and explored the potential molecular mechanisms in rats.

Methods

Rats were pretreated with 25 or 50 mg/kg crocetin 6 h prior to treating with 5 mg/kg ATO to induce hepatic injury daily for 7 days.

Results

Treatment with crocetin attenuated ATO-induced body weight loss, decreases in food and water consumption, and improved ATO-induced hepatic pathological damage. Crocetin significantly inhibited ATO-induced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) increases. Crocetin prevented ATO-induced liver malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Crocetin abrogated the ATO-induced decrease of catalase (CAT) and superoxide dismutase (SOD) activity. Crocetin was found to significantly restore the protein levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). Furthermore, crocetin promoted the expression of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADP(H): quinone oxidoreductase 1 (NQO1).

Conclusion

These findings suggest that crocetin ameliorates ATO-induced hepatic injury in rats. In addition, the effect of crocetin might be related to its role in antioxidant stress, as an anti-inflammatory agent, and in regulating the Nrf2 signaling pathway.

Authors+Show Affiliations

Department of Diagnostics, School of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, People's Republic of China.Department of Pharmaceutics, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China.Department of Pharmaceutics, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China.Department of Pharmaceutics, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China.Department of Pharmaceutics, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China.Department of Pharmaceutics, School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China.Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People's Republic of China.Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, People's Republic of China. Department of Pharmacology, School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32546959

Citation

Liu, Yanshuang, et al. "Protective Effects of Crocetin On Arsenic Trioxide-Induced Hepatic Injury: Involvement of Suppression in Oxidative Stress and Inflammation Through Activation of Nrf2 Signaling Pathway in Rats." Drug Design, Development and Therapy, vol. 14, 2020, pp. 1921-1931.
Liu Y, Liang Y, Zheng B, et al. Protective Effects of Crocetin on Arsenic Trioxide-Induced Hepatic Injury: Involvement of Suppression in Oxidative Stress and Inflammation Through Activation of Nrf2 Signaling Pathway in Rats. Drug Des Devel Ther. 2020;14:1921-1931.
Liu, Y., Liang, Y., Zheng, B., Chu, L., Ma, D., Wang, H., Chu, X., & Zhang, J. (2020). Protective Effects of Crocetin on Arsenic Trioxide-Induced Hepatic Injury: Involvement of Suppression in Oxidative Stress and Inflammation Through Activation of Nrf2 Signaling Pathway in Rats. Drug Design, Development and Therapy, 14, 1921-1931. https://doi.org/10.2147/DDDT.S247947
Liu Y, et al. Protective Effects of Crocetin On Arsenic Trioxide-Induced Hepatic Injury: Involvement of Suppression in Oxidative Stress and Inflammation Through Activation of Nrf2 Signaling Pathway in Rats. Drug Des Devel Ther. 2020;14:1921-1931. PubMed PMID: 32546959.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective Effects of Crocetin on Arsenic Trioxide-Induced Hepatic Injury: Involvement of Suppression in Oxidative Stress and Inflammation Through Activation of Nrf2 Signaling Pathway in Rats. AU - Liu,Yanshuang, AU - Liang,Yingran, AU - Zheng,Bin, AU - Chu,Li, AU - Ma,Donglai, AU - Wang,Hongfang, AU - Chu,Xi, AU - Zhang,Jianping, Y1 - 2020/05/19/ PY - 2020/02/01/received PY - 2020/04/27/accepted PY - 2020/6/18/entrez PY - 2020/6/18/pubmed PY - 2020/6/18/medline KW - Nrf2 signaling pathway KW - arsenic trioxide KW - crocetin KW - hepatotoxicity KW - inflammation KW - oxidative stress SP - 1921 EP - 1931 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 14 N2 - Purpose: Arsenic trioxide (ATO) has been shown to induce hepatic injury. Crocetin is a primary constituent of saffron, which has been verified to have antioxidant and anti-inflammatory effects. In the current experiment, we evaluated the efficacy of crocetin against ATO-induced hepatic injury and explored the potential molecular mechanisms in rats. Methods: Rats were pretreated with 25 or 50 mg/kg crocetin 6 h prior to treating with 5 mg/kg ATO to induce hepatic injury daily for 7 days. Results: Treatment with crocetin attenuated ATO-induced body weight loss, decreases in food and water consumption, and improved ATO-induced hepatic pathological damage. Crocetin significantly inhibited ATO-induced alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) increases. Crocetin prevented ATO-induced liver malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Crocetin abrogated the ATO-induced decrease of catalase (CAT) and superoxide dismutase (SOD) activity. Crocetin was found to significantly restore the protein levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α). Furthermore, crocetin promoted the expression of nuclear factor erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADP(H): quinone oxidoreductase 1 (NQO1). Conclusion: These findings suggest that crocetin ameliorates ATO-induced hepatic injury in rats. In addition, the effect of crocetin might be related to its role in antioxidant stress, as an anti-inflammatory agent, and in regulating the Nrf2 signaling pathway. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/32546959/Protective_Effects_of_Crocetin_on_Arsenic_Trioxide-Induced_Hepatic_Injury:_Involvement_of_Suppression_in_Oxidative_Stress_and_Inflammation_Through_Activation_of_Nrf2_Signaling_Pathway_in_Rats L2 - https://dx.doi.org/10.2147/DDDT.S247947 DB - PRIME DP - Unbound Medicine ER -
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