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Published on: July 29, 2014
Genistein Improves Liver Damage in Male Mice Exposed to Morphine
Mohammad Reza Salahshoor1, Shiva Roshankhah1, Payman Hosseni1
1Department of Anatomical Sciences, University of Kermanshah School of Medicine, Kermanshah, Taghbostan 6714686698, Iran.
Background:
Morphine is commonly used to treat severe pain. This substance is significantly metabolized in the liver and causes disturbing effects. Genistein is an isoflavone and has antioxidant properties. The aim of this study was to evaluate the effects of genistein against morphine damages on mouse liver.
Methods:
Between May 2017 and March 2018, 48 male mice were divided into six groups (n = 8 in each group). Various doses of genistein (25 and 50 mg/kg) and morphine plus genistein (25 and 50 mg/kg) were administered intraperitoneally to 48 male mice for 20 consequent days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum nitric oxide (NO) levels, liver weight, and the diameter of hepatocytes and central hepatic vein were studied and compared using one-way analysis of variance.
Results:
Morphine administration significantly increased the mean diameter of the central hepatic vein (22.76 ± 1.9 μm vs. 15.04 ± 0.60 μm, χ2 = 21.814, P = 0.001) and hepatocytes (3.03 ± 0.10 μm vs. 1.10 ± 0.05 μm, χ2 = 9.873, P = 0.001) respectively, blood serum NO level (38.00% ± 2.09% vs. 18.72% ± 4.40%, χ2 = 20.404, P < 0.001), liver enzyme level (AST: 111.80 ± 5.10 ng/ml vs. 81.93 ± 2.20 ng/ml, χ2 = 32.201, P < 0.0001; ALT: 45.14 ± 4.10 ng/ml vs. 35.49 ± 2.50 ng/ml, χ2 = 18.203, P < 0.0001; and ALP: 3.28 ± 0.20 ng/ml vs. 2.14 ± 0.10, χ2 = 5.04, P < 0.0001, respectively), and decreased liver weight (18.50 ± 0.90 g vs. 27.15 ± 0.50 g, χ2 = 22.415, P = 0.001) compared to saline group (0.535-0.750, P < 0.0001). However, administration of genistein plus morphine significantly enhanced liver weight (25 mg/kg: 21.15 ± 2.13 g vs. 18.50 ± 0.90 g, χ2 = 19.251, P < 0.0001; 50 mg/kg: 21.20 ± 1.00 g vs. 18.5 ± 0.9 g, χ2 = 19.502, P < 0.0001, respectively) and reduced the mean diameter of hepatocyte (25 mg/kg: 2.17 ± 0.30 μm vs. 3.03 ± 0.10 μm, χ2 = 22.780, P = 0.001; 50 mg/kg: 2.01 ± 0.20 μm vs. 3.03 ± 0.10 μm χ2 = 7.120, P = 0.001, respectively), central hepatic vein (25 mg/kg: 19.53 ± 1.00 μm vs. 22.76 ± 1.90 μm, χ2 = 20.681, P = 0.001; 50 mg/kg: 19.44 ± 1.20 μm vs. 22.76 ± 1.90 μm, χ2 = 18.451, P = 0.001, respectively), AST (25 mg/kg: 95.40 ± 5.20 ng/ml vs. 111.80 ± 5.010 ng/ml, P < 0.0001; 50 mg/kg: 90.78 ± 6.00 ng/ml vs. 111.80 ± 5.10 ng/ml, χ2 = 17.112, P < 0.0001, respectively), ALT (25 mg/kg: 35.78 ± 5.01 ng/ml vs. 45.14 ± 4.10 ng/ml, χ2 = 15.320, P < 0.0001; 50 mg/kg: 33.78 ± 2.60 ng/ml vs. 45.14 ± 4.10 ng/ml, χ2 = 14.023, P < 0.0001, respectively), ALP (25 mg/kg: 2.35 ± 0.30 ng/ml vs. 3.28 ± 0.20 ng/ml, χ2 = 4.101, P < 0.0001; 50 mg/kg: 2.34 ± 0.10 ng/ml vs. 3.28 ± 0.20 ng/ml, χ2 = 2.033, P < 0.0001, respectively), and NO levels (25 mg/kg: 25.92% ± 2.30% vs. 38% ± 2.09%, χ2 = 17.103, P < 0.0001; 50 mg/kg: 24.74% ± 4.10% vs. 38% ± 2.09%, χ2 = 25.050, P = 0.001, respectively) compared to morphine group.
Conclusion:
It seems that genistein administration might improve liver damages induced by morphine in mice.
Insights
Genistein may protect the liver from morphine-induced damage. This study found genistein administration improved liver weight and reduced liver enzymes and cell damage in mice treated with morphine.
Area of Science:
- Hepatology
- Pharmacology
- Toxicology
Background:
- Morphine, a potent analgesic, is extensively metabolized in the liver, often leading to adverse hepatic effects.
- Genistein, an isoflavone, possesses known antioxidant properties that may mitigate drug-induced toxicity.
Purpose of the Study:
- To investigate the protective effects of genistein against morphine-induced liver injury in a murine model.
- To evaluate the impact of genistein on key liver function biomarkers and histological parameters following morphine administration.
Main Methods:
- Forty-eight male mice were allocated into six groups, receiving varying doses of genistein (25 and 50 mg/kg) and morphine (with or without genistein) daily for 20 days.
- Evaluated parameters included liver enzymes (AST, ALT, ALP), nitric oxide (NO) levels, liver weight, and histological measurements of hepatocytes and central hepatic veins.
Main Results:
- Morphine significantly increased liver enzymes, NO levels, and hepatocyte/central hepatic vein diameters, while decreasing liver weight compared to controls.
- Genistein co-administration significantly counteracted these effects, improving liver weight and reducing enzyme levels, NO, and cellular damage markers.
Conclusions:
- Genistein administration demonstrates a protective effect against morphine-induced liver damage in mice.
- These findings suggest genistein as a potential therapeutic agent to ameliorate opioid-induced hepatotoxicity.
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