Alkyl chain modulated cytotoxicity and antioxidant activity of bioinspired amphiphilic selenolanes

Abstract

A series of amphiphilic conjugates of dihydroxy selenolane (DHS) and monoamine selenolane (MAS), which we had previously reported to inhibit lipid peroxidation and assist the oxidative protein folding reaction respectively in cell free systems, were evaluated for cytotoxicity, associated mechanisms and antioxidant effects in cells. Our results indicated that a fatty acid/alkyl group of variable chain lengths (C) as a lipophilic moiety of the DHS/MAS conjugates not only improved their ability to incorporate within the plasma membrane of cells but also modulated their cytotoxicity. In the concentration range of 1-50 μM, C conjugates were non-toxic whereas the long chain (≥C) conjugates showed significant cytotoxicity. The induction of toxicity investigated by the changes in membrane leakage, fluidity, mitochondrial membrane potential and annexin-V-propidium iodide (PI) staining by using flow cytometry revealed plasma membrane disintegration and subsequent induction of necrosis as the major mechanism. Further, the conjugates of DHS and MAS also showed differential as well as nonlinear tendency in cytotoxicity with respect to chain lengths and this effect was attributed to their self-aggregation properties. Compared with the parent compounds, C conjugates not only exhibited better antioxidant activity in terms of the induction of selenoproteins such as glutathione peroxidase 1 (GPx1), GPx4 and thioredoxin reductase 1 (TrxR1) but also protected cells from the AAPH induced oxidative stress. In conclusion, the present study suggests the importance of hydrophilic-lipophilic balance (HLB) in fine tuning the toxicity and activity of bioinspired amphiphilic antioxidants.

Toxicity and Antigenotoxic Effect of Hispolon Derivatives: Role of Structure in Modulating Cellular Redox State and Thioredoxin Reductase

“…Approximately, 2 μg of the total RNA was used for cDNA synthesis by reverse transcription (cDNA synthesis kit, Thermo Scientific, USA), and real-time PCR was carried out using the template (cDNA), SYBR green master mix (Roche Applied Science, Germany), and gene-specific primers in a Rotor-Gene Q (QIAGEN, Germany), according to the protocol standardized earlier. 51 The threshold cycle (CT) values estimated from the above runs for the target genes were normalized against a housekeeping gene, b-actin, according to the method described earlier. 52 The primers (forward and reverse) used for cDNA amplification are γGCL (forward): 5′-GGGGTGACGAGGTGGAGTA-3′, γGCL (reverse): 5′-GTTGGGGTTTGTCCTCTCCC-3′, βActin (forward): 5′-GGCTGTATTCCCCTCCATCG-3′, and βActin (reverse): 5′-CCAGTTGGTAACAATGCCATGT-3′.…”

“…In brief, total RNA was isolated from cells at 48 h after treatment with HS or its derivatives using the TRI reagent. Approximately, 2 μg of the total RNA was used for cDNA synthesis by reverse transcription (cDNA synthesis kit, Thermo Scientific, USA), and real-time PCR was carried out using the template (cDNA), SYBR green master mix (Roche Applied Science, Germany), and gene-specific primers in a Rotor-Gene Q (QIAGEN, Germany), according to the protocol standardized earlier . The threshold cycle (CT) values estimated from the above runs for the target genes were normalized against a housekeeping gene, b-actin, according to the method described earlier .…”

Benzene-Bridged Organosilica Modified Mesoporous Silica Nanoparticles via an Acid-Catalysis Approach

“…While for DMSNs-EB treated cells, a significantly lower cell viability was observed compared to the DMSNs-BB-1 group, suggesting the higher cytotoxicity of DMSNs-EB than DMSNs-BB-1 and the potential of DMSNs-BB-1 as biocompatible cellular delivery vehicles. The end hydrophobic organic groups have been reported to disrupt cell membrane and cause cell cytotoxicity, − while MONs with bridged hydrophobic organic groups in the framework possess better hemocompatibility and lower cytotoxicity. , Here, we directly compared the cytotoxicity difference between DMSNs-EB and DMSNs-BB-1 with end and bridged benzene groups, respectively. The higher cytotoxicity of DMSNs-EB than DMSNs-BB-1 suggests that compared to the bridged benzene group covalently connected to two silicon atoms, the end benzene group modified on the surface of DMSNs is more effective in disrupting the cell membrane.…”

Antioxidant protection by β‐selenoamines against thioacetamide‐induced oxidative stress and hepatotoxicity in mice

“…Studies have reported that antioxidant molecules protect against TAA‐induced oxidative stress . It has also been reported that selenium compounds possess numerous biological properties, mainly associated with their ability to modulate the expression of selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase …”

“…[15,16] It has also been reported that selenium compounds possess numerous biological properties, mainly associated with their ability to modulate the expression of selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase. [17,18] The main studied selenium compounds, Diphenyl diselenide and Ebselen, have been reported as promising antioxidant molecules mainly due to their GPx-like activity. [19] In this regard, new diselenides F I G U R E 1 Chemical structure of -selenoamines and monoselenides molecules are designed using DPDS and Ebs, respectively, as a prototype structure.…”