Table 1.

EDCs and liver toxicity in experimental models.

Endocrine Disruptor	Experimental Model	Dose	Duration	Effects	Ref.
Bisphenol A (BPA)	HepG2 cells	${10}^{-4}$ to ${10}^{-12}$ M	Acute: 24, 48 (and 72) h	₋Increased ROS production ₋Hyperpolarization of MMP	[50]
Bisphenol A (BPA)	HepG2 cells	10 or 100 nM	Acute: 2, 6, 12 or 24 h	₋Decreased OCR and ATP production ₋Decreased MMP ₋Increased MDA concentrations	[51]
	Mouse liver	1.2 mg/kg bw/day	Chronic: 5 days	₋Swollen mitochondria ₋Decreased OCR ₋Decreased expression of respiratory complexes III and V ₋Increased levels of MDA ₋Decreased expression of GPx3
Bisphenol A (BPA)	Mouse liver	BPA water 50 μg/kg/day	Chronic: 10 weeks	₋Increased ROS, RNS, MDA ₋Decreased activities of SOD, GPx, CAT and T-AOC ₋Decreased activity of ETS complexes I–V ₋Decreased intracellular ATP content	[56]
Bisphenol A (BPA)	Mouse liver	50 µg/kg along with HFD (after 12 weeks of HFD feeding)	Chronic: 3 weeks	₋Decreased state 3 respiration ₋Increased ROS production ₋Increased MDA levels ₋Decreased mitochondrial activity of SOD and aconitase enzymes	[58]
Bisphenol A	Mouse liver	50 mg/kg/bw along with HFCCD bw	Chronic: 8 weeks	₋Increased α-SMA and cleaved caspase 3 ₋Increased index of 8-OHdG	[59]
Bisphenol A (BPA)	Neonatal rat liver	1.47 ng/mL	Acute: 1 h	₋Swollen mitochondria	[103]
Bisphenol A (BPA)	Rat liver	30 mg/kg bw/day	Chronic: 6 weeks	₋Decreased activities of GSHPx, GR, SOD and GSH ₋Increased level of MDA	[57]
Bisphenol A (BPA)	Rat liver	50 mg/kg/day	Chronic: 4 weeks	₋Decreased levels of GSH and SOD ₋Decreased activities of GSHPx, CAT, GR and GST ₋Increased TBARS and NO	[52]
Bisphenol A (BPA)	Rat liver	150 mg/kg, 250 mg/kg and 500 mg/kg	Chronic: 14 days	₋Decreased activity of complexes I–V of ETS ₋Decreased GSH level ₋Increased LPO level ₋Increased protein carbonyl content ₋Increased production of superoxide anion ₋Decreased activity of GPx, GR and SOD dismutase	[53]
Bisphenol A (BPA)	Rat liver	10 and 50 mg/kg	Chronic: 30 days	₋Increased levels of MDA (at 50 mg/kg dosage) and H2O2 (at 10 and 50 mg/kg dosage) ₋Decreased levels of CAT, GSHPx and SOD (at 50 mg/kg dosage)	[54]
Bisphenol A (BPA)	Rat liver	0.5 mg/kg (low dose), 5 mg/kg (medium dose, NOAEL) or 50 mg/kg (high dose)	Chronic: 30 days	₋Increased levels of MDA in all treated groups ₋Decreased GSH content in all treated groups	[55]
Bisphenol A (BPA)	Rat liver	100 mg/kg	Chronic: 30 days	₋Decreased activities of CAT, SOD, POD, GSR, GST and GSH ₋Increased TBARS and H2O2 levels ₋Increased TNF-α, NF-κB, IL-6, IL-1β levels and COX-2 activity	[66]
Bisphenol A (BPA)	Rat liver	90 and 270 mg/kg bw	Chronic: 30 days	₋Decreased SOD and GSH levels (high dose) ₋Increased MDA level (high dose) ₋Decreased gene expression of PGC-1α and Nrf1 (high dose) ₋Decreased protein levels of SIRT1, PGC-1α, Nrf2 and TFAM (high dose) ₋Increased protein expression of IL-1β ₋Increased cell apoptosis by up-regulating the protein levels of Bax, cleaved-Caspase3 and cleaved-PARP1 and down-regulating the Bcl-2	[60]
Bisphenol A (BPA)	Rat liver (L-NAME-induced hypertensive Wistar rats)	50 µg/kg	Chronic: 30 days	₋Potentiated oxidative stress, ACE activity, malfunction of the antioxidant system, lipid abnormalities and inflammatory factor (TNF-α and IL-6) expression	[67]
Bisphenol A (BPA)	Rat offspring liver	40 µg/kg/day	Chronic: during gestation and lactation	₋ At 3 weeks of age: Decreased MRC activity (I and III) ₋ At 15 weeks: Restricted activities of CI, CII and CIII Decreased ATP production Increased ROS generation ₋ At 26 weeks: Decreased all MRC activities Decreased MMP Decreased ATP production Increased ROS generation	[61]
Bisphenol A	Rat liver (from pregnant rats and female postnatal day-6 offspring)	0.036 mg/kg bw/day and 3.42 mg/kg bw/day	Chronic: during premating, mating, pregnancy, lactation	₋Increased oxidative stress levels ₋Increased inflammatory response ₋Increased apoptosis pathways	[62]
Bisphenol A (BPA)	Common carp (Cyprinus carpio) liver	0.1, 1, 10, 100 and 1000 µg/L	Chronic: 30 days	₋Inhibited CAT activity (at concentrations of 100 and 1000 µg/L) ₋Decreased GSH-Px and SOD activities (at concentrations of 10, 100 and 1000 µg/L) ₋Increased LPO (assessed by MDA content) with the increase in BPA concentration (at concentrations of 100 and 1000 µg/L)	[63]
Bisphenol A (BPA)	Common carp (Cyprinus carpio) liver	4.5 and 6 mg/L	Chronic: 30 days	₋Increased levels of ROS and TBARS ₋Decreased levels of SOD, CAT POD	[64]
Bisphenol A (BPA) and S (BPS)	Rat liver	50 or 500 μg/kg/day of BPA or BPS; 50 μg/kg/day of both BPA and BPS	Chronic: 20 weeks	₋Up-regulated the expression of Sdhb (exposure to BPA or BPS) ₋Up-regulated the expression of COQ9 and COX5B (exposure to BPS) ₋Dysregulated expression of liver antioxidant enzymes	[69]
Bisphenol S (BPS)	Mouse liver	100 µg/kg/day in drinking water	Chronic: 10 weeks	₋Disrupted mitochondrial function and oxidative stress parameters	[104]
Bisphenol S (BPS)	Mouse liver	0.1–1 mM	Acute: 12 h	₋Increased ROS	[70]
Bisphenol S (BPS)	Fish (Labeo rohita) liver	Groups II, III and IV were exposed to 80 mg BPS/L, Groups V, VI and VII were exposed to 100 mg BPS/L, and Groups VIII, IX and X to 120 mg BPS/L	Chronic: 7, 14 and 21 days	₋Increased activities of SOD, CAT, GR and GSH ₋Decreased activities of GPx and GST	[72]
Bisphenols: bisphenol A (BPA), bisphenol F (BPF) and bisphenol AF (BPAF)	Mouse offspring liver	100 ng/g bw/day	Chronic: from the 7th day of pregnancy to the 21st day after delivery	₋ BPA: Decreased activities of SOD, CAT and GSH-Px and level of GSH Increased level of MDA ₋ BPF: Decreased activities of CAT and GSH	[68]
Bisphenol A (BPA) + nonylphenol (NP)	Rat liver	100 µg/kg	Chronic: 56 consecutive days	₋Increased MDA ₋Decreased activities of SOD, GSH, GSH-Px, GSH-ST, CAT and POD	[75]
Nonylphenol (NP)	Zebrafish (Danio rerio) liver	50 and 100 μg/L	Chronic: 21 days	₋Promotes ROS synthesis, more specifically, superoxide anions and H2O2 levels	[76]
Polychlorinated biphenyls (PCBs)	Rat liver	Contaminated (two times the TDI) goat milk administered daily by gavage (6 µL/g bw)	Chronic: 8 weeks	₋Decreased oxygen consumption and ATP production ₋Increased TBARS	[84]
Polychlorinated biphenyls (PCBs)—PCB126	Mouse liver	1.53 μmol/kg	Chronic: 10 weeks	₋Decreased level of GSH	[85]
Polychlorinated biphenyls (PCBs) and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)	Rat liver	TCDD at 3, 10 or 100 ng/kg/day; PCB 126 at 10, 100 or 1000 ng/kg/day; PCB 153 at 10, 100 or 1000 μg/kg/day; Binary mixture of PCB 126 and PCB 153 (10 ng/kg/day + 10 μg/kg/day, 100 ng/kg/day + 100 μg/kg/day or 1000 ng/kg/day + 1000 μg/kg/day	Chronic: 13 and 52 weeks	₋Increased mtDNA copy number (TCDD exposure and mixture of PCB126 and PCB153 exposure)	[81]
Atrazine (ATZ) and its metabolite diaminochlorotriazine (DACT)	Mouse liver	ATZ and DACT (100 and 200 mg/kg/bw, respectively)	Chronic: 1 week	₋Increased SOD activities (high dose of ATZ treated group and both of the low and high doses of DACT treated groups) ₋Decreased CAT activity (high dose of DACT treated group) ₋Increased GST activity (high dose of DACT treated group)	[86]
Atrazine (ATZ)	HepG2 cells	0.05–2 mM	Acute: 3 h and 6 h	₋Decreased ATP content ₋Down-regulation of many OXPHOS subunit expression ₋Up-regulated SOD and SIRT3 expression ₋Down-regulated TFAM and SIRT1 expression	[87]
Di (2-ethylhexyl) phthalate (DEHP)	HSC-T6 cells	50 and 100 µM	Chronic: 3.5 months	₋Decreased ability to produce ATP ₋Impaired mitochondrial maximal working capacity ₋Decreased level of spare respiratory capacity and basal oxygen consumption	[93]
Di (2-ethylhexyl) phthalate (DEHP)	Rat liver	600 mg/kg/day	Chronic: 12 weeks	₋Increased level of MDA ₋Decreased levels of SOD, CAT, GSH-Px, T-AOC and GSH/GSSG	[94]
Di (2-ethylhexyl) phthalate (DEHP)	Female quail (Coturnix japonica) liver	250, 500 and 1000 mg/kg bw/day	Chronic: 45 days	₋Increased MDA, GSH and GST ₋Decreased T-AOC, SOD and GPx ₋Induced mitochondrial ultrastructural abnormalities and mitochondrial dysfunctions ₋Activated mitochondrial unfolded protein response	[95]
Mono-(2-ethylhexyl) phthalate (MEHP)	Zebrafish liver	31.25, 62.5, 125, 250, 500 or 1000 mg/L	Acute: 24 h	₋Increased GST and GPx activities ₋Decreased MDA level ₋Increased SOD activity (125 mg/L) ₋Increased total GSH concentration (62.5 mg/L)	[96]
Perfluorooctane sulphonate (PFOS)	Rat liver	Single dose of 1 or 10 mg/kg body	Chronic: 28 consecutive days	₋Increased intracellular ROS and NO production ₋Weakened intracellular antioxidant defense by inhibiting CAT and SOD activities ₋Elevated iNOS, Bax, cytochrome c, cleaved caspase-9 and cleaved caspase-3	[97]
Polychlorinated diphenyl ethers (PCDEs)	Zebrafish liver	1, 10 and 50 μg/L	Chronic: 14 days	₋Induced oxidative stress	[99]
Endocrine disruptors mixture	Rabbit liver	10 × ADI	Chronic: 12 months	₋Decreased CAT activity ₋Increased TBARS levels	[101]

8-OHdG = 8-hydroxydeoxyguanosine; α-SMA = alpha-smooth muscle actin; ACE = angiotensin converting enzyme; ADI = acceptable daily intake; ATP = adenosine triphosphate; Bax = Bcl-2-associated X; Bcl-2 = B-cell lymphoma-2; bw = body weight; CAT = catalase; COQ9 = ubiquinone biosynthesis protein COQ9_ mitochondrial; COX-2 = cyclooxygenase-2; COX5B = cytochrome c oxidase subunit 5B mitochondrial; DACT = diaminochlorotriazine; ETS = electron transport system; GPx3 = glutathione peroxidase 3; GR = glutathione reductase; GSH = glutathione; GSHPx = glutathione peroxidase; GST = glutathione-S-transferase; GSSG = glutathione disulfide; HFCCD = high-fat/high-cholesterol/high-cholic acid diet; HFD = high-fat diet; HSC = hepatic stellate cells; IL = interleukin; iNOS = inducible nitric oxide synthase; Nrf = nuclear respiratory factor; L-NAME = Nω-nitro-l-arginine methyl ester; LPO = lipid peroxidation; MDA = malondialdehyde; MMP = mitochondrial membrane potential; MRC = mitochondrial respiratory chain; mtDNA = mitochondrial DNA; NF-κB = nuclear factor kappa-B; NO = nitric oxide; NOAEL = no adverse effect level; OCR = oxygen consumption rate; OXPHOS = oxidative phosphorylation; PARP-1 = poly [ADP-ribose] polymerase 1; PGC-1α = peroxisome proliferator-activated receptor-gamma coactivator 1α; POD = peroxidase; ROS = reactive oxygen species; RNS = reactive nitrogen species; SIRT1 = sirtuin 1; SIRT3 = sirtuin 3; SDHB = succinate dehydrogenase iron-sulfur subunit; SOD = superoxide dismutase; T-AOC = total antioxidant capacity; TBARS = thiobarbituric acid reactive substances; TDI = tolerable daily intake; TFAM = mitochondrial transcription factor A; TNF-α = tumor necrosis factor-α.