Amelioration of Metal-Induced Cellular Stress by α-Lipoic Acid and Dihydrolipoic Acid through Antioxidative Effects in PC12 Cells and Caco-2 Cells

Abstract

α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are endogenous dithiol compounds with significant antioxidant properties, both of which have the potential to detoxify cells. In this study, ALA (250 μM) and DHLA (50 μM) were applied to reduce metal (As, Cd, and Pb)-induced toxicity in PC12 and Caco-2 cells as simultaneous exposure. Both significantly decreased Cd (5 μM)-, As (5 μM)-, and Pb (5 μM)-induced cell death. Subsequently, both ALA and DHLA restored cell membrane integrity and intracellular glutathione (GSH) levels, which were affected by metal-induced toxicity. In addition, DHLA protected PC12 cells from metal-induced DNA damage upon co-exposure to metals. Furthermore, ALA and DHLA upregulated the expression of survival-related proteins mTOR (mammalian target of rapamycin), Akt (protein kinase B), and Nrf2 (nuclear factor erythroid 2-related factor 2) in PC12 cells, which were previously downregulated by metal exposure. In contrast, in Caco-2 cells, upon co-exposure to metals and ALA, Nrf2 was upregulated and cleaved PARP-1 (poly (ADP-ribose) polymerase-1) was downregulated. These findings suggest that ALA and DHLA can counterbalance the toxic effects of metals. The protection of ALA or DHLA against metal toxicity may be largely due to an enhancement of antioxidant defense along with reduced glutathione level, which ultimately reduces the cellular oxidative stress.

Alleviating effects of pea peptide on oxidative stress injury induced by lead in PC12 cells via Keap1/Nrf2/TXNIP signaling pathway

“…In this study, lead treatment could significantly decrease the level of GSH/GSSG, demonstrating its effect on the glutathione redox cycle. Lead treatment has been shown to decrease intracellular GSH levels, which is consistent with our findings ( 34 ). When preincubated with pea peptides and VC for lead treatment, PP3, PP4, PP6, and VC significantly increased GSH/GSSG and returned to normal levels compared to the lead group ( P < 0.05).…”

Dual therapy with zinc acetate and rifaximin prevents from ethanol-induced liver fibrosis by maintaining intestinal barrier integrity

“…To explore in vitro effects of zinc acetate and rifaximin on enterocytes, we used the human colorectal adenocarcinoma line Caco-2. Caco-2 cells were obtained from Riken BRC Cell Bank (Ibaraki, Japan) and were cultured, as described previously[ 32 ]. The cells were cultured in Dulbecco’s modified Eagle’s medium supplemented with 100 U/mL of penicillin, 100 g/mL of streptomycin, 0.1-mM nonessential amino acids, 10-mM HEPES, and 10% fetal bovine serum at 37 °C in an environment with 5% carbon dioxide.…”

Arsenic‐induced toxicity and the ameliorative role of antioxidants and natural compounds

“…[110,121] Studies conducted in isolated rat liver mitochondria have shown the ameliorative effect of α-LA against the Asinduced oxidative stress. [122] Studies conducted in cell line models have revealed the protection of α-LA or dihydrolipoic acid against metal (arsenic, cadmium, lead) toxicity by reducing oxidative stress through the enhancement of an antioxidant defense mechanism. [123] 8.7 | Ascorbic acid and thiamine…”