Table 2.
Summary of studies evaluating Se effects on AsIII-induced toxicity in animal and cell culture models
| Duration of Se treatment | Se type | Se dose | Model | Main target | Effects of Se on the toxicity of AsIII | References |
|---|---|---|---|---|---|---|
| 6–14 days | Na2SeO3 | 0.025 mg Se kg−1 BW oral (drinking water) | Pregnant Syrian hamster | Fetus | ↓ As content in the brain, liver, kidney, bladder, and skin of pregnant animals; ↓ As accumulation in placenta and whole fetuses; ↓ primary and ↑ secondary methylation index in urine and tissues of dams and in whole fetuses; ↓ activities of GR, SOD1, and CAT, which were increased by As; further increase in the activity of GPx, which was already increased by As; ↑ viable fetuses and ↓ nonviable fetuses and fetal resorptions; partly prevented As-mediated body weight loss in pups | [89] |
| 3 weeks | Na2SeO3 | 3 mg kg−1 BW oral intubation | Wistar rat | Liver | ↓ AST, ALT, and ALP activities in plasma compared to As-treated animals; ↑ GSH level and GPx activity, ↓ lipid peroxidation and GST activity; ↓ As-induced histological changes such as cytoplasmic vacuolization | [90] |
| 3 weeks | Na2SeO3 | 3 mg kg−1 BW oral intubation | SD rat | Liver | Partly protected against an As-induced increase in liver weights; ↓ AST and ALT activities in serum, which were increased by As; ↓ levels of MDA, NO, advanced oxidation protein products, and serum IL-6, which were elevated by As; ↑ TrxR and TAC activities; ↑ mRNA gene expression of Nrf2, which was decreased by As; ↓ As-mediated histopathological changes such as inflammatory cellular infiltration | [91] |
| 20 weeks | Na2SeO3 | 17.0 mg L−1 oral | SD rat | Liver | ↓ ALT and AST activities in the blood, which were increased by As; ↓ lipid peroxidation; ↑ GPx activity, which was reduced by As; ↑ mRNA expression of GPx, CAT, SOD1, Txnrd1, and protein expression of TrxR, which were reduced by As; ↓ As-induced HSP70 and HO-1 protein expression | [92] |
| 50 days | SeMet | 2 ppm oral (in diet) | C57BL/6 N mouse | Liver | Se did not have an effect on As excretion in urine; ↑ lipid peroxidation in the liver of Se-only–treated mice and As-treated mice | [93] |
| 2 h | Na2SeO3 | 1, 5, and 10 μM | Poeciliopsis lucida hepatocellular carcinoma cell line (PLHC-1) | ↓ As-induced cytotoxicity and the ROS level after 10-h As exposure; ↑ GPx activity, which was reduced by As; partly protected from mitochondrial membrane potential damage induced after 10 and 20 h As exposure; ↓ As-mediated apoptosis after short As exposure (10 h) but ↑ As-mediated apoptosis in the case of longer As exposure (40 h) | [94] | |
| 13 weeks | Not specified (Se-rich lentils) | 0.009 (Se-deficient), 0.16 (Se-adequate), 0.3 mg Se kg−1 (Se-high) oral | ApoE−/− mouse | Heart, liver | Se-high diet reduced or prevented atherosclerotic plaque formation in the aortic sinus and aortic arches, respectively, compared to Se-deficient and Se-adequate diets; Se-adequate and Se-high diet increased the HDL:LDL ratio, which was decreased by As; Se-adequate and Se-high diet decreased GSH levels and increased the GSSG level in the livers of As-treated mice, compared to Se-deficient diet. | [95] |
| 14 weeks | Not specified (Se-rich lentils) | < 0.01 ppm Se (Se-deficient), 0.3 ppm Se (Se-high) oral | Wistar rat | Blood, kidney, liver | Se-high diet reduced As levels in kidney but increased As levels in urine, and feces, compared to Se-deficient diet; ↑ GSH levels in blood, which were reduced in Se-deficient diet; mitigated hepatic lipid peroxidation; partly recovered antibody response, which was reduced in Se-deficient animals | [96] |
| 6 weeks | Na2SeO3 | 3 mg/kg BW oral intubation | SD rat | Kidney, heart | ↓ plasma renal markers (urea, creatinine, blood urea nitrogen), which were increased by As; ↓ As-induced lipid peroxidation in the kidney and heart; ↑ kidney and heart levels of GSH, SOD, and CAT, which were decreased by As; ↓ cardiac risk factors such as plasma triglyceride levels, which were increased by As; ↓ histopathological changes in renal tissue | [97] |
| 24 h | SeMet | 100 μM | Human embryonic kidney cell line (HEK-293) | ↓ As-induced cytotoxicity and the ROS level; enhanced phosphorylation of proteins involved in ROS detoxification, antitumor activity, and cell growth | [98] | |
| 1 h | SeNPs | 0.01 μg μL−1 | Human lymphocytes | Nanoselenium prevented As-induced cytotoxicity and DNA damage | [99] | |
| 48 h | Na2SeO3 | 10 μM | Rat pheochromocytoma cell line (PC12) | ↓ As content; ↓ As-induced LDH leakage to the culture medium; ↑ GSH levels and GPx activity, which were reduced by As; ↓ lipid peroxidation; ↑ expression of proteins involved in inhibition of autophagy (mTOR, Akt), which were downregulated by As; ↓ As-induced upregulation of proteins that induce autophagy (p62, ubiquitin); ↑ expression of antiapoptotic proteins (bcl2, NF-κB, ERK1) and ↓ proapoptotic proteins (Bax, caspase-3); ↓ mRNA expression of caspase-9, which was increased by As | [100] | |
↑, increased; ↓, decreased