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Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice.
World J Gastroenterol 2015; 21(14):4195-209WJ

Abstract

AIM

To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water (HRW) in acetaminophen (APAP)-induced liver injury in mice.

METHODS

Male mice were randomly divided into the following four groups: normal saline (NS) control group, mice received equivalent volumes of NS intraperitoneally (ip); HRW control group, mice were given HRW (same volume as the NS group); APAP + NS group, mice received NS ip for 3 d (5 mL/kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d (same as NS treatment) after APAP challenge. In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates. In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg. Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury.

RESULTS

Treatment with HRW resulted in a significant increase in the 5-d survival rate compared with the APAP + NS treatment group (60% vs 26.67%, P < 0.05). HRW could significantly decrease the serum alanine aminotransferase level (24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P < 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P < 0.01; and 3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P < 0.05, respectively) and aspartate aminotransferase level (24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P < 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P < 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group. The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result. Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels. The liver index (5.16% ± 0.26% vs 5.88% ± 0.073%, P < 0.05) and percentage of liver necrosis area (27.73% ± 0.58% vs 36.87% ± 0.49%, P < 0.01) were significantly lower in the HRW-treated animals. The malonyldialdehyde (MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group (10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P < 0.05). A decrease in superoxide dismutase (SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected (9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P < 0.05). Furthermore, HRW could significantly increase the glutathione (GSH) contents (878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group. Meanwhile, HRW could reduce the inflammation level (serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P < 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P < 0.01, respectively). In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502E expression. Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration.

CONCLUSION

HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.

Authors+Show Affiliations

Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Jing-Yao Zhang, Si-Dong Song, Qing Pang, Rui-Yao Zhang, Yong Wan, Chang Liu, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25892869

Citation

Zhang, Jing-Yao, et al. "Hydrogen-rich Water Protects Against Acetaminophen-induced Hepatotoxicity in Mice." World Journal of Gastroenterology, vol. 21, no. 14, 2015, pp. 4195-209.
Zhang JY, Song SD, Pang Q, et al. Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice. World J Gastroenterol. 2015;21(14):4195-209.
Zhang, J. Y., Song, S. D., Pang, Q., Zhang, R. Y., Wan, Y., Yuan, D. W., ... Liu, C. (2015). Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice. World Journal of Gastroenterology, 21(14), pp. 4195-209. doi:10.3748/wjg.v21.i14.4195.
Zhang JY, et al. Hydrogen-rich Water Protects Against Acetaminophen-induced Hepatotoxicity in Mice. World J Gastroenterol. 2015 Apr 14;21(14):4195-209. PubMed PMID: 25892869.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice. AU - Zhang,Jing-Yao, AU - Song,Si-Dong, AU - Pang,Qing, AU - Zhang,Rui-Yao, AU - Wan,Yong, AU - Yuan,Da-Wei, AU - Wu,Qi-Fei, AU - Liu,Chang, PY - 2014/10/17/received PY - 2014/12/17/revised PY - 2015/02/12/accepted PY - 2015/4/21/entrez PY - 2015/4/22/pubmed PY - 2016/1/27/medline KW - Acetaminophen KW - Connexin 32 KW - Hydrogen KW - Liver regeneration KW - Reactive oxygen species SP - 4195 EP - 209 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 21 IS - 14 N2 - AIM: To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water (HRW) in acetaminophen (APAP)-induced liver injury in mice. METHODS: Male mice were randomly divided into the following four groups: normal saline (NS) control group, mice received equivalent volumes of NS intraperitoneally (ip); HRW control group, mice were given HRW (same volume as the NS group); APAP + NS group, mice received NS ip for 3 d (5 mL/kg body weight, twice a day at 8 am and 5 pm) after APAP injection; APAP + HRW group, mice received HRW for 3 d (same as NS treatment) after APAP challenge. In the first experiment, mice were injected ip with a lethal dose of 750 mg/kg APAP to determine the 5-d survival rates. In the second experiment, mice were injected ip with a sub-lethal dose of 500 mg/kg. Blood and liver samples were collected at 24, 48, and 72 h after APAP injection to determine the degree of liver injury. RESULTS: Treatment with HRW resulted in a significant increase in the 5-d survival rate compared with the APAP + NS treatment group (60% vs 26.67%, P < 0.05). HRW could significantly decrease the serum alanine aminotransferase level (24 h: 4442 ± 714.3 U/L vs 6909 ± 304.8 U/L, P < 0.01; 48 h: 3782 ± 557.5 U/L vs 5111 ± 404 U/L, P < 0.01; and 3255 ± 337.4 U/L vs 3814 ± 250.2 U/L, P < 0.05, respectively) and aspartate aminotransferase level (24 h: 4683 ± 443.4 U/L vs 5307 ± 408.4 U/L, P < 0.05; 48 h: 3392 ± 377.6 U/L vs 4458 ± 423.6 U/L, P < 0.01; and 3354 ± 399.4 U/L vs 3778 ± 358 U/L, respectively) compared with the APAP treatment group. The alkaline phosphatase, total bilirubin and lactate dehydrogenase levels had the same result. Seventy-two hours after APAP administration, liver samples were collected for pathological examination and serum was collected to detect the cytokine levels. The liver index (5.16% ± 0.26% vs 5.88% ± 0.073%, P < 0.05) and percentage of liver necrosis area (27.73% ± 0.58% vs 36.87% ± 0.49%, P < 0.01) were significantly lower in the HRW-treated animals. The malonyldialdehyde (MDA) contents were significantly reduced in the HRW pretreatment group, but they were increased in the APAP-treated group (10.44 ± 1.339 nmol/mg protein vs 16.70 ± 1.646 nmol/mg protein, P < 0.05). A decrease in superoxide dismutase (SOD) activity in the APAP treatment group and an increase of SOD in the HRW treatment group were also detected (9.74 ± 0.46 U/mg protein vs 12.1 ± 0.67 U/mg protein, P < 0.05). Furthermore, HRW could significantly increase the glutathione (GSH) contents (878.7 ± 76.73 mg/g protein vs 499.2 ± 48.87 mg/g protein) compared with the APAP treatment group. Meanwhile, HRW could reduce the inflammation level (serum TNF-α: 399.3 ± 45.50 pg/L vs 542.8 ± 22.38 pg/L, P < 0.05; and serum IL-6: 1056 ± 77.01 pg/L vs 1565 ± 42.11 pg/L, P < 0.01, respectively). In addition, HRW could inhibit 4-HNE, nitrotyrosine formation, JNK phosphorylation, connexin 32 and cytochrome P4502E expression. Simultaneously, HRW could facilitate hepatocyte mitosis to promote liver regeneration. CONCLUSION: HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/25892869/Hydrogen_rich_water_protects_against_acetaminophen_induced_hepatotoxicity_in_mice_ L2 - http://www.wjgnet.com/1007-9327/full/v21/i14/4195.htm DB - PRIME DP - Unbound Medicine ER -