Table 2.
Catechins in fetal alcohol spectrum disorders.
| Author (Year) | Objective | Type of Study and Sample Size | Inclusion and Exclusion Criteria | Interventions | Methodology | Main Outcomes | Conclusion | Quality of Evidence |
|---|---|---|---|---|---|---|---|---|
| Antonio and Druse, 2008 [78] | To investigate the protective effect of EGCG against ethanol-associated apoptosis in rhombencephalic neurons | In-vitro model of rhombencephalic neurons in culture | Culture of rhombencephalic tissue from GD 14 rat fetuses | 24-h ethanol treatment of rhombencephalic neurons with 75 mM ethanol. Co-treatment with 75 mM ethanol and 1 µM EGCG |
TUNEL for detection and quantification of apoptotic nuclei | Ethanol ↑ apoptosis in fetal rhombencephalic neurons (p < 0.01). EGCG ↓ apoptotic rhombencephalic neurons (p < 0.01) |
The treatment with EGCG provides neuroprotection to the ethanol-treated neurons | + |
| Long et al., 2010 [79] | To evaluate the role of oxidative stress in FASD and the effect of EGCG in the prevention of ethanol-induced embryonic damage | Mouse model. Five experimental groups (n = 6 per group) |
C57BL/6J pregnant female mice. Five experimental groups: (1) control, (2) ethanol 0.005 mL/g, (3) ethanol 0.01 mL/g, (4) ethanol 0.015 mL/g, (5) ethanol 0.02 mL/g +/−EGCG | Ethanol ip (25%, 0.005–0.02 mL/g) on GD8. EGCG intragastric gavage (200, 300 or 400 mg/Kg/day) on GD7–8 in 0.02 mL/g ethanol exposed group |
Morphology assessment (GD10.25): HL, HW and CRL. Analysis of neural marker genes and proteins (GD9.25) by RT-PCR and western blot Study of neural marker genes and proteins. Measure H2O2 and MDA on GD9.25 |
Ethanol ↑ growth restriction (HL, HW, and CRL). Ethanol ↓ Otx1 and Sox2. Ethanol ↑ H2O2 and MDA. EGCG ↓ embryo growth restriction EGCG ↑ Otx1 and Sox2 |
Embryo growth restriction in FASD is mediated by overproduction of ROS. Ethanol affects neural marker genes and proteins involved in brain development and neural differentiation. EGCG has a protective effect against FASD |
+ |
| Tiwari et al., 2010 [80] | To assess the effect of EGCG on ethanol-induced biochemical alterations and behavioral disorders | Rat model. Five experimental groups (n = 5–8 per group). |
Wistar male rat pups (five-day-old neonates). Five experimental groups: (1) control, (2) ethanol administration, (3) ethanol + EGCG administration (50 mg/Kg), (4) ethanol + EGCG administration (100 mg/Kg), (5) EGCG administration (100 mg/Kg) |
Randomization of the pups into five experimental groups. Ethanol administration (5 g/Kg, 12% v/v) by intragastric gavage. EGCG (50 and 100 mg/kg). |
Behavioral tests: MWM test, memory consolidation test, elevated plus maze task. BAC quantification. Acetylcholinesterase activity measurement. Lipid peroxidation, glutathione, superoxide dismutase, catalase and nitrite, TNF-α and IL-1β estimation by ELISA. NF-κB p65 unit quantification. Caspase-3 colorimetric assay |
Ethanol ↓ scores in MWM elevated plus maze task. Ethanol ↑ acetylcholinesterase activity, oxidative-nitrosative stress, cytokines (TNF-α and IL-1β), NF- κB and caspase-3 levels. EGCG ↓ behavioral and biochemical ethanol-induced alterations |
Cognitive disorders in FASD are associated with oxidative-nitrosative stress-mediated apoptotic signaling. EGCG is useful in the prevention of FASD-related cognitive impairment |
++ |
| Almeida et a., 2021 [81] | To analyze the effects of PAE according two human drinking patterns (Mediterranean vs. binge) on placenta and brain development and evaluate the effect of EGCG treatment on FASD development | Mouse model. Six experimental groups (n = 6 per group) |
C57BL/6 pregnant mice. Six experimental groups: (1) control med, (2) EtOH med, (3) EtOH med + EGCG, (4) control bin, (5) EtOH bin, (6) EtOH bin + EGCG | Ethanol administration by intragastric gavage from GD0 to GD19, 10% v/v, 1.5 g/Kg/day or 3 g/Kg/day. EGCG 30 mg/Kg/day by intragastric gavage. Cesarean section at GD19 |
Fetal and placental weights. Western blot (VEGF-A, PLGF, VEGF-R1, Nrf2, NeuN, DCX, GFAP and BDNF). Immunohistochemistry (VEGF-A, PLGF, VEGF-R1, NeuN, DCX and BDNF). Immunofluorescence (Nrf2 and GFAP) |
Ethanol ↓ fetal growth (growth was negatively correlated with ethanol dose). Ethanol ↓ VEGF-A and ↓ VEGF-R1. Ethanol ↓ Nrf2. Ethanol ↓ NeuN, ↑ DCX and ↓ GFAP. EGCG ↓ ethanol-induced oxidative stress ameliorating FASD manifestations |
Any drinking pattern may produce fetal growth, loss of mature neurons, delay in neuronal maturation and disorders in astrocyte differentiation (the highest doses cause to the most severe disturbances) EGCG ameliorates FASD alterations |
+ |
Abbreviations: EGCG: epigallocatechin-3-gallate; GD: gestational day; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling; HL: head length; HW: head width; CRL: crown rump length; Oxt1: orthodenticle homolog 1 (Drosophila); Sox2: sex determining region of Y chromosome (Sry); H2O2: hydrogen peroxide; MDA: malondialdehyde; ROS: radical oxygen species; PND: postnatal days; MWM: Morris water maze; BAC: blood alcohol concentration; TNF: tumor necrosis factor; IL: interleukin; NF- κB: nuclear factor kappa-light-chain-enhancer of activated B cells; FASD: fetal alcohol spectrum disorders; PAE: prenatal alcohol exposure; Med: Mediterranean; Bin: binge; EtOH: ethanol; VEGF-A: vascular endothelial growth factor A; PLGF: placental growth factor; VEGF-R1: vascular endothelial growth factor receptor 1; Nrf2: nuclear factor erythroid 2-related factor 2; NeuN: neuronal nuclei; DXC: doublecortin; GFAP: glial fibrillary acidic protein; BDNF: brain-derived neurotrophic factor. ↑: increment; ↓: reduction. Quality of evidence grades: moderate (+++), low (++), very low (+).