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Protective Effects of Facilitated Removal of Blood Alcohol and Acetaldehyde Against Liver Injury in Animal Models Fed Alcohol and Anti‐HIV Drugs
Author(s) -
Han Hui,
He Yuxin,
Johnson Heather,
Mishra Pratibha,
Lee Harrison,
Ji Cheng
Publication year - 2019
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.14034
Subject(s) - acetaldehyde , liver injury , alcohol , lipogenesis , inflammation , ethanol , chemistry , alcoholic hepatitis , pharmacology , alcoholic liver disease , medicine , biochemistry , cirrhosis , lipid metabolism
Background We previously developed enzyme nanoparticles ( ENP ) of alcohol metabolism. This study was to evaluate protective effects of facilitated removal of blood alcohol and/or acetaldehyde on anti‐ HIV drugs and alcohol‐induced liver injuries. Methods ENP were prepared for degrading alcohol completely ( ENP 1) or partially into acetaldehyde ( ENP 2), which were applied to mice of acute binge or chronic‐binge alcohol feeding in the presence of antivirals (ritonavir and lopinavir). Liver pathologies were examined to assess the protective effects of ENP . Results In the acute model, ENP 1 and ENP 2 reduced the blood alcohol concentration (BAC) by 41 and 32%, respectively, within 4 hr, whereas in control without ENP , BAC was reduced only by 15%. Blood acetaldehyde concentration ( BADC ) was increased by 39% in alcohol‐fed mice treated with ENP 2 comparing to control. No significant effects of the anti‐ HIV drugs on BAC or BADC were observed. Plasma alanine aminotransferase ( ALT ) and expression of liver TNF ‐ α were both significantly increased in the alcohol‐fed mice, which were normalized by ENP 1. In the presence of the antivirals, ALT was partially reduced by ENP 1 or ENP 2. In the chronic model, inflammation, fatty liver, and ALT were increased, which were deteriorated by the antivirals. ENP 1 partially reduced BAC , BADC , ALT , and expression of inflammation markers of TNF ‐ α , F4/80, and IL ‐6 and lipogenic factors of ACC , LXR α , and SREBP 1. ENP 2 reduced BAC without significant effects on ALT , inflammation, or lipogenesis. Antivirals and alcohol synergistically increased expression of organelle stress markers of CHOP , sXBP ‐1, ATF 6, and GCP 60. ENP 1 reduced BAC , CHOP , and sX bp‐1. However, no effects of ENP 1 were found on ATF 6 or GCP 60. Conclusions Removal of blood alcohol and acetaldehyde by the ENP protects the liver against alcoholic injuries, and the protection is less effective in chronic alcohol and antiviral feeding due to additional drug‐induced organelle stresses.