Effects of Melatonin on Liver Injuries and Diseases
Abstract
:1. Introduction
2. Protective Effects of Melatonin on Liver Injuries
2.1. Protective Effects of Melatonin on Chemical Pollutant-Induced Liver Injuries
2.2. Protective Effects of Melatonin on Drug-Induced Liver Injuries
2.3. Protective Effects of Melatonin on Alcohol-Induced Liver Injury
2.4. Protective Effects of Melatonin on Other Factor-Induced Liver Injuries
3. Protective Effects of Melatonin on Hepatic Steatosis
4. Protective Effects of Melatonin on Non-Alcoholic Fatty Liver
5. Protective Effects of Melatonin on Hepatitis
6. Protective Effects of Melatonin on Liver Fibrosis
7. Protective Effects of Melatonin on Liver Cirrhosis
8. Protective Effects of Melatonin on Hepatocarcinoma
9. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Toxins | Subjects | Methods of Melatonin Administration | Duration of Melatonin Treatment | Melatonin Doses | Melatonin Effects | Ref. |
---|---|---|---|---|---|---|
Methanol | Rats | Intragastric gavage | 6 or 24 h | 10 mg/kg BW or 3 g/kg BW | Reducing the MDA level significantly, restoring the protein carbonylation level, preventing the increase in nitrite level and MPO activity and the reduction in the antioxidant enzyme activities, and returning piecemeal necrosis, lobular lytic necrosis and portal inflammation to normal histologic appearances at a dose of 10 mg/kg | [46] |
Fluoride | Mice | Peritoneal injection | 30 days | 10 mg/kg BW/daily | Preventing the decrease in body and liver weight as well as the decrease in liver enzyme activity of succinate dehydrogenase (SDH), acid phosphatase (ACP), alkaline phosphatase (ALP), and total liver protein level and diminishing the increase in serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities in the liver | [47] |
Aluminum chloride | Rats | Oral administration | 30 days | 5 mg/kg BW/daily | Alleviating the increases in the plasma of the ALT, AST, ALP, total bilirubin, total lipids, total cholesterol, TG and glucose levels, and attenuating the decrease in total proteins, reducing oxidative stress, and improving histological changes | [48] |
Dimethyl-nitrosamine | Rats | Intraperitoneal injection | 14 days | 50 mg/kg BW/daily | Improving serum and antioxidant enzyme activities, reducing the infiltration of inflammatory cells and necrosis in the liver, and increasing the expression of nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase-1, HO-1, and SOD2, and increasing novel transcription factor expression, nuclear erythroid 2-related factor 2(Nrf2) and decreasing inflammatory mediators expression | [49] |
Thio-acetamide | Rats | Intraperitoneal injection | 24 h | 3 mg/kg BW | Decreasing serum liver enzymes and blood ammonia levels, improving liver histological changes, decreasing mortality of rats, inhibiting the increase in nuclear binding of nuclear factor kappa B (NFκB), and decreasing the hepatic level of thiobarbituric acid reactive substances, protein carbonyls and inducible NO synthase, improving survival and reducing liver damage and oxidative stress | [50] |
Nicotine | Rats | Subcutaneous injection | 30 days | 10 mg/kg BW/daily | Attenuating the increase in LPO products and restoring the SOD activity and GSH level, and reducing both nitrotyrosine reactivity and tissue damage | [51] |
Paraquat | Rats and hepatocytes | Preincubation with melatonin in vitro | 30 min | 0.5, 1 or 2 mM | Preventing in a dose- and time- dependent manner the loss of viability, the leakage of lactate dehydrogenase, depletion of intracellular glutathione and MDA accumulation, and inhibiting cell damage completely at 2 mM dose | [52] |
Factors | Subjects | Methods of Melatonin Administration | Duration of Melatonin Treatment | Melatonin Doses | Melatonin Effects | Ref. |
---|---|---|---|---|---|---|
Liver resection | Patients | Through a nasogastric tube | A single dose | 50 mg/kg BW | Resulting in lower postoperative transaminases, and inducing a trend toward shorter ICU stay and total hospital stay | [99] |
Bile duct ligation | Rats | Injection or oral administration | 8 days | 500 μg/kg BW/daily, and 10, 100 mg/kg BW daily | Resulting a significant recovery of antioxidant enzymes and a reduction in the negative parameters of cholestasis at the concentration of 500 mg/kg, and attenuating cholestatic liver injury and reducing the increases in serum and hepatic TBARS concentrations and hepatic MPO activity at the concentration of 10 and 100 mg/kg | [100,101] |
Hemorrhagic shock | Rats | Intravenous injection | A single dose | 2 mg/kg BW | Normalizing liver Akt phosphorylation, increasing mTOR activation and HO-1 expression, and reducing cleaved caspase-3 level | [102] |
Experimental hyperthyroid | Rats | Intraperitoneal injection | 20 days | 6 mg/kg BW/daily | Increasing the number of Kupffer cells, lipid vacuoles of Ito cells and microvilli of hepatocytes, and enlarging the spaces of disse | [103] |
Hyperphenylalaninemia | Rats | Subcutaneous injection | From mating day until delivery | 20 mg/kg BW/daily | Preventing the accumulation of LPO products | [104] |
High cholesterol diet | Mice | Oral administration | 4 months | 10 mg/L in drinking water | Reducing plasma, liver cholesterol, hepatic MDA, diene conjugate (DC) and liver TG levels, increasing hepatic α-tocopherol and ascorbic acid levels and liver GSH-Px and GST activities, and attenuating the histopathological lesions | [105,106] |
Constant light exposure | Rats | Subcutaneous injection | 14 days | 1 mg/kg BW/daily | Decreasing lipid peroxidation, and increasing GSH-Px activity | [107] |
Intensive exercise | Rats | Intra-peritoneal injection | 10 days | 10 mg/kg BW/daily | Increasing the parameters of enzymes in serum, liver and kidney, and decreasing cellular degenerations | [108] |
Bacillus Calmette Guerin and lipopolysaccharide | Mice, kupffer cells and hepatocytes | Using feeding needle in vivo or culture in vitro | 10 days in vivo or 48 h in vitro | 0.25, 1.0, 4.0 mg/kg BW/daily in vivo, 10−9, 10−8, 10−7, 10−6, 10−5 M in vitro | Decreasing serum ALT, AST activities at the concentration of 0.25, 1.0, 4.0 mg/kg, reducing MDA content, pro-inflammatory mediators (TNF-α, IL-1, NO) and immigration of inflammatory cells, upregulating SOD, attenuating the area and extent of necrosis and inhibiting TNF-α at the concentrations of 10−8–10−6 M, and decreasing IL-1 production of kupffer cells at the concentration of 10−6 M | [109] |
Opisthorchis viverrini | Hamsters | Oral administration | 30 days | 5, 10, and 20 mg/kg BW/daily | Decreasing the formation of oxidative and nitrosative DNA lesions, 8-oxo-7, 8-dihydro-2’-deoxyguanosine, 3-nitrotyrosine and 8-nitroguanine in the nucleus of bile duct epithelium and inflammatory cells, reducing the HO-1 expression, mRNA expression of oxidant-generating genes (inducible NO synthase, NFκB, and cyclooxygenase-2) and proinflammatory cytokines (TNF-α and IL-1β), cytokeratin 19, nitrate/nitrite, 8-isoprostane and vitamin E levels, ALT activity and bile duct proliferation in the liver and increasing antioxidant genes (Nrf2 and Mn-SOD) expression | [110] |
Rabbit hemorrhagic disease virus | Rabbits | Dissolved into dilutions | 24 h | 10 or 20 mg/kg BW | Inhibiting autophagic response significantly, and attenuating apoptosis | [111,112] |
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Zhang, J.-J.; Meng, X.; Li, Y.; Zhou, Y.; Xu, D.-P.; Li, S.; Li, H.-B. Effects of Melatonin on Liver Injuries and Diseases. Int. J. Mol. Sci. 2017, 18, 673. https://doi.org/10.3390/ijms18040673
Zhang J-J, Meng X, Li Y, Zhou Y, Xu D-P, Li S, Li H-B. Effects of Melatonin on Liver Injuries and Diseases. International Journal of Molecular Sciences. 2017; 18(4):673. https://doi.org/10.3390/ijms18040673
Chicago/Turabian StyleZhang, Jiao-Jiao, Xiao Meng, Ya Li, Yue Zhou, Dong-Ping Xu, Sha Li, and Hua-Bin Li. 2017. "Effects of Melatonin on Liver Injuries and Diseases" International Journal of Molecular Sciences 18, no. 4: 673. https://doi.org/10.3390/ijms18040673
APA StyleZhang, J.-J., Meng, X., Li, Y., Zhou, Y., Xu, D.-P., Li, S., & Li, H.-B. (2017). Effects of Melatonin on Liver Injuries and Diseases. International Journal of Molecular Sciences, 18(4), 673. https://doi.org/10.3390/ijms18040673