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Objective The aim of this study was to investigate the impact and mechanisms of emodin on oxidative stress response in lipopolysaccharide (LPS)-induced murine mononuclear macrophages (RAW264.7). Methods Involved the use of LPS, RAW264.7 cells, and emodin. Experimental groups included a control group, LPS (1 µg/mL) group, and LPS (1 µg/mL) + emodin (15 µmmol/L) pretreatment group. Aldehyde malondialdehyde (MDA) content, intracellular reactive oxygen species (ROS) levels, and silent information regulator 2 (Sirt2) expression were evaluated at 6, 12, and 18 hours after LPS exposure. Additionally, RAW264.7 cells were pretreated with Sirt2 inhibitor AGK2 (20 «mol/L) followed by LPS stimulation, and the above-mentioned parameters were assessed at 6 hours. Results Compared to the control group, MDA content, ROS levels, Sirt2 mRNA, and protein expression in RAW264.7 cells in the LPS group increased at all time points (all P < 0.05). At 6 and 18 hours, MDA content and ROS levels in RAW264.7 cells in the LPS + emodin group decreased significantly (all P < 0.05), while at 12 hours, ROS levels were lower in the LPS group compared to the LPS + emodin group (P < 0.05). Sirt2 mRNA and protein levels significantly increased at all time points (all P < 0.05) compared to the LPS group. In the LPS + emodin + AGK2 group, Sirt2 mRNA and protein levels decreased, and MDA content and ROS levels increased compared to the LPS + emodin group (all P < 0.05) .Conclusion LPS-induced oxidative stress in RAW264.7 cells and emodin attenuate LPS-induced oxidative stress in RAW264.7 cells through Sirt2. [ABSTRACT FROM AUTHOR]

In the study, we examined whether the silent information regulator 1 (SIRT1) can attenuate oxidative stress in the brains of mice carrying the APP/PS1 double mutation and/or in primary neonatal rat neurons exposed to oligomers of amyloid-β peptide (AβOs). Starting at 4 or 8 months of age, the transgenic mice were treated with resveratrol (RSV, a stimulator of SIRT1) or suramin (an inhibitor) (each 20 mg/kg BW/day) for two months. The primary neurons were exposed to AβOs (0.5 μM) for 48 h and thereafter RSV (20 μM) or suramin (300 mg/ml) for 24 h. Cell viability was assessed by the CCK-8 assay; SIRT1 protein and mRNA determined by western blotting and real-time PCR, respectively; senile plaques examined immunohistochemically; ROS monitored by flow cytometry; and the contents of OH-, H2O2, O2·-, and MDA, and the activities of SOD and GSH-Px measured by standard biochemical procedures. In comparison to wild-type mice or untreated primary neurons, the expression of SIRT1 was significantly lower in the brains of APP/PS1 mice or neurons exposed to AβOs. In these same systems, increased numbers of senile plaques and a high level of oxidative stress were apparent. Interestingly, these two latter changes were attenuated by treatment with RSV, but enhanced by suramin. These findings indicate that SIRT1 may be neuroprotective. [ABSTRACT FROM AUTHOR]

Increasing evidence showed that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are common event in the pathophysiology of many vascular diseases, including atherosclerosis and restenosis after angioplasty. Among the underlying mechanisms, oxidative stress is one of the principal contributors to the proliferation and migration of VSMCs. Oxidative stress occurs as a result of persistent production of reactive oxygen species (ROS). Recently, the protective effects of peroxisome proliferator-activated receptor γ (PPARγ) against oxidative stress/ROS in other cell types provide new insights to inhibit the suggests that PPARγ may regulate VSMCs function. However, it remains unclear whether activation of PPARγ can attenuate oxidative stress and further inhibit VSMC proliferation and migration. In this study, we therefore investigated the effect of PPARγ on inhibiting VSMC oxidative stress and the capability of proliferation and migration, and the potential role of mitochondrial uncoupling protein 2 (UCP2) in oxidative stress. It was found that platelet derived growth factor-BB (PDGF-BB) induced VSMC proliferation and migration as well as ROS production; PPARγ inhibited PDGF-BB-induced VSMC proliferation, migration and oxidative stress; PPARγ activation upregulated UCP2 expression in VSMCs; PPARγ inhibited PDGF-BB-induced ROS in VSMCs by upregulating UCP2 expression; PPARγ ameliorated injury-induced oxidative stress and intimal hyperplasia (IH) in UCP2-dependent manner. In conclusion, our study provides evidence that activation of PPARγ can attenuate ROS and VSMC proliferation and migration by upregulating UCP2 expression, and thus inhibit IH following carotid injury. These findings suggest PPARγ may represent a prospective target for the prevention and treatment of IH-associated vascular diseases. [ABSTRACT FROM AUTHOR]

The protective role of lovastatin against neurotoxicity induced by fluorosis was investigated by using primary hippocampal neurons. The cholesterol content, activity of superoxide dismutase (SOD), and content of malondialdehyde (MDA) were measured by biochemical assays. The cell viability was assessed by examining the rate of apoptosis by flow cytometry. The results showed that high fluoride inhibited activity of SOD and increased levels of MDA and apoptosis in the primary neurons. Interestingly, certain dosages of lovastatin, without changing the cholesterol level, attenuated these neurotoxicities resulting from high exposure to fluoride in the primary cultured neurons. The results suggest that lovastatin may play a protective role against the neurotoxicity induced by an excessive amount of fluoride. [ABSTRACT FROM AUTHOR]

Maintenance of male reproductive function depends on normal sperm generation during which process Sertoli cells play a vital role. Studies found that fine particulate matter (PM) causes decreased male sperm quality, mechanism of which unestablished. We aim to investigate the definite mechanism of PM impairment on male reproduction. Male Sprague-Dawley rats were daily exposed to normal saline (NS) or PM 2.5 with the doses of 9 mg/kg.b.w and 24 mg/kg.b.w. via intratracheal instillation for seven weeks. Reproductive function was tested by mating test and semen analysis after last exposure. Testes were collected to assess changes in histomorphology, and biomarkers including connexin 43 (Cx43), superoxide dismutase (SOD), phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (p-Akt). Male rats exposed to PM 2.5 showed noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate and severe testicular damage in histomorphology. After PM 2.5 exposure, the levels of Cx43 was significantly downregulated, and SOD was upregulated and downregulated significantly with different dose, respectively. Protein expression of PI3K and p-Akt dramatically enhanced, and the later one being located in Sertoli cells, the upward or declining trend was in dose dependent. PM 2.5 exposure leads to oxidative stress impairment via PI3K/Akt signaling pathway on male reproduction in rats. [ABSTRACT FROM AUTHOR]