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Curcumin protects against acetaminophen-induced apoptosis in hepatic injury
Gang Li1, Jun-Bao Chen, Chao Wang
1Gang Li, Jun-Bao Chen, Chao Wang, Zhi Xu, Hao Nie, Xiao-Yan Qin, Xiao-Mei Chen, Quan Gong, Department of Immunology, School of Medicine, Yangtze University, Jingzhou 434023, Hubei Province, China.
Aim:
To explore the effects of curcumin (CMN) on hepatic injury induced by acetaminophen (APAP) in vivo.
Methods:
Male mice were randomly divided into three groups: group I (control) mice received the equivalent volumes of phosphate-buffered saline (PBS) intraperitoneally (ip); Group II [APAP + carboxymethylcellulose (CMC)] mice received 1% CMC (vehicle) 2 h before APAP injection; Group III (APAP + CMN) mice received curcumin (10 or 20 mg/kg, ip) 2 h before before or after APAP challenge. In Groups II and III, APAP was dissolved in pyrogen-free PBS and injected at a single dose of 300 mg/kg. CMN was dissolved in 1% CMC. Mice were sacrificed 16 h after the APAP injection to determine alanine aminotransferase (ALT) levels in serum and malondialdehyde (MDA) accumulation, superoxide dismutase (SOD) activity and hepatocyte apoptosis in liver tissues.
Results:
Both pre- and post-treatment with curcumin resulted in a significant decrease in serum ALT compared with APAP treatment group (10 mg/kg: 801.46 ± 661.34 U/L; 20 mg/kg: 99.68 ± 86.48 U/L vs 5406.80 ± 1785.75 U/L, P < 0.001, respectively). The incidence of liver necrosis was significantly lowered in CMN treated animals. MDA contents were significantly reduced in 20 mg/kg CMN pretreatment group, but increased in APAP treated group (10.96 ± 0.87 nmol/mg protein vs 16.03 ± 2.58 nmol/mg protein, P < 0.05). The decrease of SOD activity in APAP treatment group and the increase of SOD in 20 mg/kg CMN pretreatment group were also detected (24.54 ± 4.95 U/mg protein vs 50.21 ± 1.93 U/mg protein, P < 0.05). Furthermore, CMN treatment efficiently protected against APAP-induced apoptosis via increasing Bcl-2/Bax ratio.
Conclusion:
CMN has significant therapeutic potential in both APAP-induced hepatotoxicity and other types of liver diseases.
Insights
Curcumin (CMN) effectively protects against acetaminophen (APAP)-induced liver injury in mice. Both pre- and post-treatment with CMN significantly reduced liver damage markers and apoptosis, highlighting its therapeutic potential.
Area of Science:
- Pharmacology
- Hepatology
- Toxicology
Background:
- Acetaminophen (APAP) overdose is a leading cause of acute liver failure.
- Curcumin (CMN), a natural compound, possesses known anti-inflammatory and antioxidant properties.
- Investigating CMN's protective effects against APAP-induced hepatotoxicity is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of curcumin (CMN) in mitigating liver injury caused by acetaminophen (APAP) in a murine model.
- To assess the impact of CMN on key biomarkers of hepatic damage and oxidative stress following APAP challenge.
Main Methods:
- Male mice were administered APAP (300 mg/kg) and treated with varying doses of CMN (10 or 20 mg/kg) either before or after APAP exposure.
- Control groups received vehicle (carboxymethylcellulose or PBS) instead of CMN.
- Liver injury was assessed by measuring serum alanine aminotransferase (ALT) levels, liver malondialdehyde (MDA) and superoxide dismutase (SOD) activity, and hepatocyte apoptosis.
Main Results:
- Curcumin treatment significantly reduced serum ALT levels and liver necrosis compared to the APAP-only group.
- CMN administration, particularly at 20 mg/kg, decreased MDA accumulation and increased SOD activity, indicating reduced oxidative stress.
- Curcumin effectively inhibited APAP-induced hepatocyte apoptosis by modulating the Bcl-2/Bax ratio.
Conclusions:
- Curcumin demonstrates significant hepatoprotective effects against APAP-induced liver injury in vivo.
- CMN exhibits therapeutic potential for treating APAP-induced hepatotoxicity and potentially other forms of liver disease.
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