Involvement of oxidative stress-related apoptosis in chlorpyrifos-induced cytotoxicity and the ameliorating potential of the antioxidant vitamin E in human glioblastoma cells.

Organophosphate pesticides (OPs), which are among the most widely used synthetic chemicals for the control of a wide variety of pests, are however associated with various adverse reactions in animals and humans. Chlorpyrifos, an OP, has been shown to cause various health complications due to ingestion, inhalation, or skin absorption. The mechanisms underlying the adverse effect of chlorpyrifos on neurotoxicity have not been elucidated. Therefore, we aimed to determine the mechanism of chlorpyrifos-induced cytotoxicity and to examine whether the antioxidant vitamin E (VE) ameliorated these cytotoxic effects using DBTRG-05MG, a human glioblastoma cell line. The DBTRG-05MG cells were treated with chlorpyrifos, VE, or chlorpyrifos plus VE and compared with the untreated control cells. Chlorpyrifos induced a significant decrease in cell viability and caused morphological changes in treated cultures. Furthermore, chlorpyrifos led to the increased production of reactive oxygen species (ROS) accompanied by a decrease in the level of reduced glutathione. Additionally, chlorpyrifos induced apoptosis by upregulating the protein levels of Bax and cleaved caspase-9/caspase-3 and by downregulating the protein levels of Bcl-2. Moreover, chlorpyrifos modulated the antioxidant response by increasing the protein levels of Nrf2, HO-1, and NQO1. However, VE reversed the cytotoxicity and oxidative stress induced by chlorpyrifos treatment in DBTRG-05MG cells. Overall, these findings suggest that chlorpyrifos causes cytotoxicity through oxidative stress, a process that may play an important role in the development of chlorpyrifos-associated glioblastoma.

Vitamin E and selenium partially prevent cytotoxicity, oxidative stress and DNA damage induced by T-2 toxin in bovine Leydig cells.

The objective of this study was to explore the protective mechanism of Vitamin E (VE) and selenium (Se) against T-2 toxin-induced oxidative damage of bovine Leydig cells. Leydig cells were isolated, cultured and divided into five treatment groups such as: control, T-2, Se + T-2, VE + T-2 and VE + Se + T-2. After treatment for 24 h, the cells and supernatants were harvested to examine the cell viability, the activities and mRNA expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT), the content of malondialdehyde (MDA) and DNA damage. Results showed that T-2 toxin exposure significantly reduced the cell viability, increased the MDA level, reduced GSH-Px, SOD and CAT activities and increased DNA damage (P < 0.05). Meanwhile, T-2 toxin was attributed to the down-regulation of the mRNA expression of GSH-Px, SOD and CAT (P < 0.05). However, VE and Se reduced T-2 toxin-induced oxidative damage and tended to maintain normal levels (P < 0.05). Furthermore, VE and Se substantially up-regulated the activities and mRNA expressions of the GSH-Px, SOD and CAT. In conclusion, VE and Se, due to its anti-oxidative ability, could ameliorate T-2 toxin-induced cytotoxicities by regulating oxidative stress in bovine Leydig cells.

D-004 ameliorates phenylephrine-induced urodynamic changes and increased prostate and bladder oxidative stress in rats.

BACKGROUND: Lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) mainly depend on alpha1-adrenoreceptors (α1-ADR) stimulation, but a link with oxidative stress (OS) is also involved. D-004, a lipid extract of Roystonea regia fruits, antagonizes ADR-induced responses and produces antioxidant effects. The objective of this study was to investigate whether D-004 produce antioxidant effects in rats with phenylephrine (PHE)-induced urodynamic changes. METHODS: Rats were randomized into eight groups (ten rats/group): a negative vehicle control and seven groups injected with PHE: a positive control, three treated with D-004 (200, 400 and 800 mg/kg) and three others with tamsulosin (0.4 mg/kg), grape seed extract (GSE) (250 mg/kg) and vitamin E (VE) (250 mg/kg), respectively. RESULTS: Effects on urinary total volume (UTV), volume voided per micturition (VM), malondialdehyde (MDA) and carbonyl groups (CG) concentrations in prostate and bladder homogenates were study outcomes. While VM and UTV lowered significantly in the positive control as compared to the negative control group, the opposite occurred with prostate and bladder MDA and CG values. D-004 (200-800 mg/kg) increased significantly both VM and UTV, lowered significantly MDA in prostate and bladder homogenates, and reduced GC levels only in the prostate. Tamsulosin increased significantly VM and UTV, but unchanged oxidative variables. GSE and VE unchanged the UTV, whereas VE, not GSE, modestly but significantly attenuated the PHE-induced decrease of VM. CONCLUSIONS: Single oral administration of D-004 (200-800 mg/kg) was the only treatment that ameliorated the urodynamic changes and reduced increased oxidative variables in the prostate of rats with PHE-induced prostate hyperplasia.