TABLE 3.
DHA exposures across various models
| Model-system | Dose | Key findings | References |
|---|---|---|---|
| Cell models | |||
| A375P | 5 mM | Inhibited cell growth; increases in ROS; no DNA damage; cell cycle arrest; delayed induction of apoptosis; increased mitochondrial polarization | Smith et al., 2018 |
| HaCaT | 5 to 100 mM | No change in cell proliferation with 25 mM dose after 3 hr; cell cycle arrest (50% increase of cells in the G2/M); doses greater than 25 mM induced cell death; apoptosis; increase in DNA strand breaks | Petersen et al., 2004 |
| HaCaT | Cell viability analysis by flow cytometry and cell proliferation: ≤50 mM; detection of intracellular oxidative stress: ≤40 mM; comet assay (alkaline single cell gel electrophoresis): 20 mM; detection of γH2AX (S139): ≤40 mM | Impaired cell viability, proliferation, and cell cycle progression, increased gene expression of HMOX1 due to oxidative stress, increased XRCC2 and ERCC3 gene expression due to DNA damage, increased AGE formation, increased ROS (only for greater than 40 mM) | Perer et al., 2020 |
| HEK293T | |||
| HEK293T | 5 mM | Cell cycle arrest confirmed by increased cyclin A2 and cyclin B1 levels; no apoptosis as exposure did not lead to cleavage of PARP1 or Caspase 3; autophagy confirmed with increase in LC3BII to LC3BI ratio and SIRT1 expression; reduced mitochondrial membrane potential after 24 hr exposure; initial decline in OCR; decline in ECAR after 24 hr, decreased ATP production and lactate production; NAD+/NADH cofactor imbalances | Smith et al., 2019 |
| Animal model systems, human samples, and bacteria | |||
| C57BL/6 mice | 8 mM | Exogenous DHA readily enter cells and tissues and form metabolites | Moreno et al., 2014 |
| Sprague–Dawley rats | 80 mM of hyperpolarized [2-13C] DHA | Generation of different metabolites in liver and kidneys; higher levels of DHA and DHAS in the kidney than the liver | Marco-Rius et al., 2017 |
| Skin biopsy samples from pig | 5, 10, and 20% DHA | DHA increases free radical production by 180% in UV-exposed skin relative to the control untreated group | Jung et al., 2008 |
| Human serum albumin | Reaction mixtures included 2, 10, or 30 mM of each DHA or DHAP and 35 mg of HAS | HSA is shown to undergo glycation by DHA | Seneviratne et al. 2012 |
| Salmonella typhimurium strain TA100 | 8% DHA | DHA cytotoxicity with and without metabolic activation; DHA is mutagenic and can lead to DNA damage | Pham et al., 1979 |