Abstract
Cisplatin (CP) is one of the most effective antitumor drugs in the clinic, but has serious adverse reactions, and its hepatotoxicity has not been fully investigated. Licorice (GC), a traditional herbal medicine, has been commonly used as a detoxifier for poisons and drugs, and may be an effective drug for CP-induced hepatotoxicity. However, its mechanism and the effector molecules remain ambiguous. Therefore, in this study, a network pharmacology and proteomics-based approach was established, and a panoramic view of the detoxification of GC on CP-induced hepatotoxicity was provided. The experimental results indicated that GC can recover functional indices and pathological liver injury, inhibit hepatocyte apoptosis, upregulate B-cell lymphoma/leukemia 2 (Bcl-2) and superoxide dismutase (SOD) levels, and downregulate cellular tumor antigen p53 (p53), caspase-3, malondialdehyde high mobility group protein B1 (HMGB1), tumor necrosis factor alpha (TNF-α), and interleukin 1β (IL-1β) levels. Proteomics indicated that GC regulates phosphatidylcholine translocator ABCB1 (ABCB1B), canalicular multispecific organic anion transporter 1 (ABCC2), cytochrome P450 4A2 (CYP4A2), cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2), estrogen receptor (ESR1), and DNA topoisomerase 2-alpha (TOP2A), inhibits oxidative stress, apoptosis, and inflammatory responses, and accelerates drug metabolism. In this study, we provide the investigation of the efficacy of GC against CP-induced hepatotoxicity, and offer a promising alternative for the clinic.
Highlights
Cisplatin (CP) has been widely used in ovarian cancer, prostate cancer, testicular cancer, and others, due to its potent penetration and wide anticancer spectrum (Dasari and Tchounwou, 2014)
Antibodies directed against phosphatidylcholine translocator ABCB1 (ABCB1B), canalicular multispecific organic anion transporter 1 (ABCC2), cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2), estrogen receptor 1 (ESR1), and DNA topoisomerase 2-alpha (TOP2A) were purchased from Abcam Biotechnology Co. (Milton, Cambridge, UK)
We observed the possibility of detoxification and revealed the molecular mechanism of GC to CP by establishing a CP-induced hepatotoxicity model in rats
Summary
Cisplatin (CP) has been widely used in ovarian cancer, prostate cancer, testicular cancer, and others, due to its potent penetration and wide anticancer spectrum (Dasari and Tchounwou, 2014). The accumulation of CP in the liver is second only to that in the kidney (Bandu et al, 2015), whereas limited attention has been paid to hepatotoxicity, and the underlying mechanism, as well as protective drugs, has not been thoroughly studied. GC possesses significant hepatoprotective activities to liver injury by CCl4 or acetaminophen (Kuang et al, 2017; Wu et al, 2020). Some antioxidant enzymes, such as superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), can be induced by GC (Hejazi et al, 2017). It has previously been reported that functional indices in CP-induced liver injury recovered by administration of GC (Lee et al, 2007), functional characteristics and underlying mechanism have not yet been elucidated
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