Hepatotoxicity of Brucea javanica bitter alcohol in nude mice based on liver drug metabolizing enzyme CYP450 expression
ZOU Hong, QI Shuo, LI Dandan, DENG Fangping, CHEN Shuangshuang, FU Shuxin, TANG Zheng, TANGQun
2025, 30(8):
1049-1057.
doi:10.12092/j.issn.1009-2501.2025.08.005
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AIM: Hepatotoxicity of Brucea javani
ca picryl with broad-spectrum anticancer effect in
nude mice based on hepatic drug metabolizing en
zyme CYP450 activity. METHODS: Fifty-six nude
mice were randomly divided into blank group, Bru
cea javanica low-dose group (2 mg/kg), Brucea ja
vanica high-dose group (4 mg / kg), and cisplatin weight after taking materials, and calculate the liv
er coefficient (liver weight/weight mass×100%), ob
serve and record the liver color and morphology.
Hematoxylin-eosin (HE) staining was used to ob
serve the pathological changes of liver tissue. De
tection of alanine aminotransferase (ALT), aspar
tate aminotransferase (AST), lactate dehydrogenase
(LDH), alkaline phosphatase (AKP) and albumin
(ALB) levels in serum of nude mice by ELISA. Real
time PCR and Western blot were used to detect
the mRNA and protein expression levels of CYP2E1,
CYP3A11, CYP2C19, CYP1A2, CYP2D6 and CYP2C9,
which were key enzymes of drug metabolism in
nude mice liver. RESULTS: Compared with the blank
group, the mortality rate of nude mice in the low
dose Brucea javanica bitter alcohol group was 0,
the growth state was good, the diet, movement,
and mental state were normal, the weight change
and liver coefficient ratio were consistent, the liver
color was ruddy, the liver lobule morphology was
complete under the microscope, the structure was
clear, the liver cells were arranged regularly, and
there was no inflammatory cell infiltration. There
was no significant difference in the content of ALT,
AST, LDH, AKP, and ALB. There was no significant
difference in the mRNA and protein expression of
CYP2E1, CYP3A11, CYP2C19, CYP1A2, CYP2D6, and
CYP2C9 (all P>0.05). Compared with the blank
group, the mortality rate of nude mice in the high
dose group of Brucea javanica bitter alcohol was
14.3%, the growth state was slightly poor, the diet,
movement, and mental state were reduced, the
weight growth was slow, the liver coefficient ratio
was increased, the liver color was reddish brown,
some liver lobule boundaries were unclear, a small group (2 mg/kg), with 14 mice in each group. The
blank group was injected with the same amount of
normal saline every 3 days for 6 weeks.Calculate
the mortality rate of nude mice in each group, ob
serve the general growth state of nude mice, re
cord the weight change of nude mice before and af
ter administration, weigh and record the liver number of liver cells were loosely arranged, the
contents of ALT, AST, LDH, AKP, and ALB were signif
icantly increased, the mRNA levels of CYP2E1,
CYP3A11, CYP2C19, CYP1A2, CYP2D6, and CYP2C9
were significantly reduced, and the protein expres
sions of CYP2E1, CYP3A11, CYP1A2, and CYP2D6
were significantly reduced (all P < 0.05 or P < 0.01),
but there was no statistical difference in the mRNA
and protein expression of CYP2C19, and the pro
tein expression of CYP2C9 (P>0.05).Compared with
the blank group, the mortality rate of nude mice in
the cisplatin group was 35.7%, the growth state
was poor, the diet, action, and mental state were
low, the weight gain was less, the liver coefficient
ratio was significantly increased, the liver color was
dark red, the liver sinusoids and central veins were
congested, the hepatocytes were disordered, the
nuclei were consolidated and contracted, and the
arrangement was loose, the contents of ALT, AST,
LDH, AKP, and ALB were significantly increased, and
the mRNA and protein expressions of CYP2E1,
CYP3A11, CYP2C19, CYP1A2, CYP2D6, and CYP2C9
were significantly reduced (all P < 0.05 or P < 0.01).
CONCLUSION: The dose of Brucea javanica bitter
alcohol is correlated with hepatotoxicity to nude
mice. High doses of Brucea javanica bitter alcohol
have hepatotoxicity to nude mice, which may be re
lated to reducing serum levels of ALT, AST, LDH,
AKP, and ALB, inhibiting the expression of multiple
subtypes of enzymes in the key enzyme CYP450 of
liver drug metabolism, and then reducing the me
tabolism of toxic substances.
