Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy

These authors contributed equally to this work.
Version 1 : Received: 8 May 2023 / Approved: 9 May 2023 / Online: 9 May 2023 (08:34:59 CEST)

A peer-reviewed article of this Preprint also exists.

Zhang, S.; Zheng, Y.; Du, H.; Zhang, W.; Li, H.; Ou, Y.; Xu, F.; Lin, J.; Fu, H.; Ni, X.; Chang, L.-J.; Shu, G. The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy. Molecules 2023, 28, 4849. Zhang, S.; Zheng, Y.; Du, H.; Zhang, W.; Li, H.; Ou, Y.; Xu, F.; Lin, J.; Fu, H.; Ni, X.; Chang, L.-J.; Shu, G. The Pathophysiological Changes and Clinical Effects of Tetramethylpyrazine in ICR Mice with Fluoride-Induced Hepatopathy. Molecules 2023, 28, 4849.

Abstract

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Keywords

acute fluorosis; tetramethylpyrazine; liver; oxidative damage; Nrf2

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

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