Table 3.
Studies included in our systematic review focusing on the effects of acute ethanol intake and exposure on animal models.
| First Author, Year | Models and Methods | Summary of Effects |
|---|---|---|
| Samuvel et al., 2022 [42] | Male C57BL/6 mice gavaged one dose ethanol (2–6 g/kg in normal saline, 20 µL/g body weight). | Acute ethanol treatment induces dose-dependent mitochondrial depolarization, leading to type 2 mitophagy sequestration (probably through the PINK1–Parkin pathway) and subsequent lysosomal processing. |
| Chen et al., 2021 [32] | Male C57BL/6 mice gavaged a total of 4.5 g/kg (body weight) of ethanol over 24 h. | Acute ethanol exposure induces autophagy and ROS-generating CYP2E1 and NOX4 enzymes. NOX4 and CYP2E1 overexpression significantly increases autophagy. Ethanol and H2O2 (but not acetaldehyde) induce autophagy in primary mouse hepatocytes. Antioxidants efficiently block CYP2E1- and NOX4-mediated autophagy induction. |
| Yan et al., 2019 [43] | Male/female C57BL/6 mice; ethanol (5 g/kg body weight) gavage for 16 h. | Atg5-KO mice are more susceptible to acute alcohol treatment, but liver damage is unexpectedly improved with the chronic plus binge model. |
| Liu et al., 2019 [34] | Male C57BL/6 mice gavaged a total of 10 mL/kg 55% ethanol over 12 h. | Mice overexpressing ALR have less liver damage with alcohol exposure, associated with the upregulation of autophagy markers and downregulation of p62 and mTOR phosphorylation. Autophagy is inhibited in ALR-KO mice. |
| Eid et al., 2016 [12] | Adult male Wistar rats given one intraperitoneal ethanol dose (40% v/v, 5 g/kg) over 24 h. | Ethanol induces a low level of hepatocyte apoptosis but enhances mitophagic vacuole formation (increased LC3 puncta formation and co-localization of Parkin and LC3). PINK1 and Parkin are located around damaged mitochondria in the hepatocytes of ethanol-treated rats with an enhanced formation of mitochondrial spheroids. |
| Williams et al., 2015 [44] | Male C57BL/6J mice gavaged with a total of 4.5 g/kg of ethanol per kg of body weight over 16 h. | Parkin prevents liver damage in an acute alcoholic model. Ethanol-fed Parkin-KO mice exhibit severe mitochondrial damage; reduced mitophagy, β-oxidation, mitochondrial respiration; and cytochrome C oxidase activity. |
| Manley et al., 2014 [45] | Male C57BL mice gavaged with a total of 4.5 g/kg ethanol per kg of body weight ethanol over 16 h. | FXR-KO mice have exacerbated hepatotoxicity, steatosis, decreased essential autophagy-related gene expression, increased Akt activation, and decreased FOXO3a activity. Ethanol treatment induces hepatic mitochondrial spheroid formation in FXR-KO, but not WT, mice. |
| Ni et al., 2013 [46] | Male C57BL/6 mice gavaged with a total of 4.5 g/kg ethanol per kg of body weight ethanol over 6, 12, and 16 h. | Ethanol-fed mice have increased mRNA and protein levels of autophagy-related genes in hepatocytes and FOXO3a activity. Suppressing FOXO3a activity in hepatocytes inhibits autophagy-related gene expression and enhances cell death, steatosis, and liver damage. A SIRT1 agonist enhances ethanol-induced autophagy-related gene expression by increasing FOXO3a deacetylation. |
| Lin et al., 2013 [47] | Intraperitoneal ethanol (33%, v/v, 1.2 g/kg body weight) injection over 10 min. | Macroautophagy is activated under acute conditions. Hepatic steatosis and liver damage are exacerbated by autophagy inhibition and alleviated by autophagy activation. |
| Yang et al., 2012 [48] | Male SV/129 and C57BL/6J mice intraperitoneally injected with ethanol (0.93 g/kg body weight) and later gavaged three times (total: 3.75 g/kg body weight) over 18 h. | WT mice show CYP2E1 activation; increased oxidative stress, JNK signaling, and SREBP expression; and decreased autophagy. Acute alcohol-induced fatty liver and oxidative stress are blunted in CYP2E1-KO and JNK inhibitor-treated mice. N-acetylcysteine decreases acute alcohol-induced oxidative stress, JNK activation, and steatosis but not CYP2E1 activation. Acute alcohol-induced fatty liver is the same in JNK1 and JNK2-KO mice as in WT mice. |
| Thomes et al., 2012 [49] | Female C57Bl/6 mice gavaged a total of 6 g/kg body weight ethanol over 12 h; precision-cut liver slices treated with 50 mM ethanol over 12–24 h. | Acute ethanol administration elevates autophagosomes without affecting hepatic proteasome activity. Liver slices show inhibited proteasome activity and enhanced autophagosome expression depending on ethanol oxidation. |
| Ding et al., 2010 [38] | Male C57BL/6 mice gavaged with a total of 4.5 g/kg ethanol per kg of body weight over 16 h. | Ethanol-induced autophagy in vivo requires ethanol metabolism, ROS generation, and mTOR signaling inhibition. Increasing autophagy reduces acute ethanol hepatotoxicity and steatosis. |
PINK1, tensin homolog-induced putative kinase 1; NOX4, nicotinamide adenine dinucleotide phosphate oxidase 4; CYP2E1, cytochrome P450 2E1; Atg 5, antithymocyte globulin 5; LC3, microtubule-associated protein light chain 3; ALR, liver regeneration-associated protein; mTOR, mammalian target of rapamycin complex 1; KO, knockout; WT, wild-type; ALR, augmenter of liver regeneration; FXR, Farnesoid X receptor; akt, protein kinase B; FOXO3a, forkhead box O3a; SIRT1, sirtuin-1; JNK1/2, c-Jun N-terminal kinase 1/2; SREBP, sterol regulatory element-binding protein.