The Disturbance of Hepatic and Serous Lipids in Aristolochic Acid Ι Induced Rats for Hepatotoxicity Using Lipidomics Approach

Abstract

Aristolochic acid I (AAI) was regarded as the major toxic component of aristolochic acid (AA). In addition to aristolochic acid nephropathy (AAN), liver cancers induced by AAI has aroused increasing attention recently. In this paper, the discovery of diagnostic biomarkers for AAI-induced liver injury has been studied, especially for the lipid markers. From the histopathological characteristics, the injury was observed clearly in the liver apart from the kidney after 30 mg/kg of AAΙ treatment for one week, while the lesion alleviated after AAΙ discontinuance. The serum biochemical indexes were manifested to the normal tendency after AAΙ discontinuance for two weeks. According to the evaluation of pathology slices and serum biochemical indexes, they indicated that the hepatotoxicity induced by AAΙ was reversible to some extent. A total of 44 lipid markers were identified in the liver, as well as 59 in the serum. Twenty-six common lipid markers were observed in both serum and liver. Furthermore, nine out of 26 lipids exhibited the excellent diagnostic ability to differentiate the control group from the AAΙ group and AAΙ discontinuance group with high sensitivity and specificity. The changed lipid markers might serve as characteristics to explain the mechanisms of pathogenesis and progression in hepatotoxicity induced by AAΙ.

Integration of Transcriptomic and Metabolomic Data to Compare the Hepatotoxicity of Neonatal and Adult Mice Exposed to Aristolochic Acid I

“…We measured AST, ALT and TBIL to evaluate the degree of liver injury, but there was no significant change in either neonatal or adult mice. Similarly, one study reflected that AST or ALT decreased to the level of the control group on the 14th day after oral- administration of 30 mg/kg AAI in male SD rats (Zhou et al, 2019). The findings suggested that liver cells were damaged in the early stage and may be repaired in the later stage.…”

“…Then, in the AAI-treated neonatal mice, AAI disturbed the phospholipid metabolic process and promoted arachidonic acid metabolism to release inflammatory factors. A previous study revealed that phospholipase A2 (PLA2) is responsible for catalyzing phosphatidylcholine transfer to hemolytic lecithin, accompanied by the release of arachidonic acid and fatty acids (Zhou et al, 2019). In the metabolic pathway, phosphatidylcholine was converted into LysoPC (22:4 (7Z, 10Z, 13Z, 16Z)/0:0) (by 1.9735-fold) and arachidonic acid to generate leukotriene D4 (LD4) (by 3.4274-fold).…”

“…One study verified that canines had precancerous lesions in the liver after 10 days of oral administration of AAI (Jin et al, 2016). Another study indicated that exposure to short-term AAI in vivo and in vitro only showed a potential liver cancer-causing effect (Rossiello et al, 1993;Zhou et al, 2019). A recent paper demonstrated that AAI promoted clonal expansion but did not induce hepatocellular carcinoma in the liver of adult rats (Liu et al, 2021).…”

Aristolochic Acid I-Induced Hepatotoxicity in Tianfu Broilers Is Associated with Oxidative-Stress-Mediated Apoptosis and Mitochondrial Damage

“…Overall, the present results indicate that AA-I can cause an increase in the liver index and the elevation of serum GOT and GPT, which is in accordance with the results from Yeh et al’s study in 2008 [ 36 ]. It has been reported that AA-I can induce diffuse hepatocyte swelling and vacuolar degeneration in rats [ 37 ]. Similarly, the current result of histopathological changes indicated that AA-I caused hepatocyte injury in a dose-dependent manner and the histopathological changes are characterized by obvious hepatocyte swelling, vesicular degeneration and steatosis.…”