2. Academic Validation
  3. A novel perspective on the preventive treatment of hydrazine compound-induced liver injury: Isoniazid liver injury as an example

A novel perspective on the preventive treatment of hydrazine compound-induced liver injury: Isoniazid liver injury as an example

  • J Ethnopharmacol. 2023 May 12;116616. doi: 10.1016/j.jep.2023.116616.
Xinyu Li 1,  Chengxian Li 2,  Chenyi Li 3,  Chengzhao Wu 4,  Yuxuan Bai 5,  Xu Zhao 6,  Zhaofang Bai 7,  Xigang Zhang 8,  Xiaohe Xiao 9,  Ming Niu 10
Affiliations

Affiliations

  • 1 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: 1204471852@qq.com.
  • 2 Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China. Electronic address: 996110125@qq.com.
  • 3 Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 Dongda Street, Fengtai District, Beijing, 100071, China; College of Pharmaceutical Science, Dali University, Dali, 671000, China. Electronic address: lichenyi0037@163.com.
  • 4 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: wcz1006@126.com.
  • 5 Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 Dongda Street, Fengtai District, Beijing, 100071, China. Electronic address: 1776241632@qq.com.
  • 6 Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: xuzhao080@outlook.com.
  • 7 Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: baizf2008@hotmail.com.
  • 8 Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 Dongda Street, Fengtai District, Beijing, 100071, China. Electronic address: zhangxg101@sina.com.
  • 9 College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Liver Disease, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China. Electronic address: pharmacy302xxh@126.com.
  • 10 Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, No. 8 Dongda Street, Fengtai District, Beijing, 100071, China. Electronic address: nmbright@163.com.
PMID: 37182677 DOI: 10.1016/j.jep.2023.116616
Abstract

Ethnopharmacological relevance: Anethum graveolens L. (dill), which has been used as a medicine, spice and aromatic plant since ancient times, is not only a traditional Chinese medicines but also an important medicinal and functional food in Europe and Central and South Asia. In ethnomedicine, dill reportedly exerts a protective effect on the liver and has been widely used as a traditional medicine for the treatment of jaundice in the liver and spleen and inflammatory gout diseases in Saudi Arabia. Furthermore, studies have found that dill can regulate the NAT2 Enzyme, and this plant was thus selected to study its alleviating effect on isoniazid liver injury.

Aim of the study: The purpose of this study was to explore the effect of dill on alleviating liver injury induced by hydrazine compounds represented by isoniazid through the use of network pharmacology combined with in vivo and in vitro experimental verifications.

Materials and methods: First, we screened the key targets of dill in the treatment of liver injury through the use of network pharmacology; we then performed GO and KEGG pathway enrichment analyses using the DAVID database. We also verified the alleviative and anti-inflammatory effects of dill on isoniazid liver injury in rats by animal experiments. We further investigated the modulating effect of dill on the enzymatic activity of NAT2, a common metabolizing Enzyme of hydrazine compounds.

Results: A total of 111 key targets were screened through network pharmacology. In vivo experiments showed that dill reduced the amount of inflammatory factors produced by isoniazid, such as IL-10, IL-1β, TNF-α and IL-6, restored the levels of ALT, AST, r-GT, AKP and TBA in vivo, and attenuated isoniazid liver injury. Both in vivo and vitro results indicated that dill could regulate the expression of NAT2 Enzymes.

Conclusions: The results tentatively demonstrate that dill can alleviate isoniazid liver injury through multiple components, targets and pathways and exerts a regulatory effect on the NAT2 Enzyme, and these findings thus provide new ideas for subsequent studies on hydrazide liver injury--reducing the risk of hydrazide-induced liver injury through anti-inflammation and regulation of NAT2 Enzymes.

Keywords

Hydrazine; Isoniazid; Liver injury; N-acetyltransferase2; Network pharmacology.

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