Diindolylmethane Inhibits Cadmium-Induced Autophagic Cell Death via Regulation of Oxidative Stress in HEL299 Human Lung Fibroblasts.

Cadmium (Cd), a harmful heavy metal, can lead to various pulmonary diseases, including chronic obstructive pulmonary disease (COPD), by inducing cytotoxicity and disturbing redox homeostasis. The aim of the present study was to investigate Cd-mediated cytotoxicity using human lung fibroblasts and the therapeutic potential of 3,3'-diindolylmethane (DIM). Cadmium significantly reduced the cell viability of human embryonic lung (HEL299) cells accompanied by enhanced oxidative stress as evidenced by the increased expression of autophagy-related proteins such as LC3B and p62. However, treatment with DIM significantly suppressed autophagic cell death in Cd-induced HEL299 fibroblasts. In addition, DIM induced antioxidant enzyme activity and decreased intracellular reactive oxygen species (ROS) levels in Cd-damaged HEL299 cells. This study suggests that DIM effectively suppressed Cd-induced lung fibroblast cell death through the upregulation of antioxidant systems and represents a potential agent for the prevention of various diseases related to Cd exposure.

Comparative toxicities of BPA, BPS, BPF, and TMBPF in the nematode Caenorhabditis elegans and mammalian fibroblast cells.

Bisphenol A (BPA) is a chemical compound commonly used in the production of plastics for daily lives and industry. As BPA is well known for its adverse health effects, several alternative materials have been developed. This study comprehensively analyzed the toxicity of BPA and its three substitutes including bisphenol S (BPS), bisphenol F (BPF), and tetramethyl bisphenol F (TMBPF) on aging, healthspan, and mitochondria using an in vivo Caenorhabditis elegans (C. elegans) model animal and cultured mammalian fibroblast cells. C. elegans treated with 1 mM BPA exhibited abnormalities in the four tested parameters related to development and growth, including delayed development, decreased body growth, reduced reproduction, and abnormal tissue morphology. Exposure to the same concentration of each alternative including TMBPF, which has been proposed as a relatively safe BPA alternative, detrimentally affected at least three of these events. Moreover, all bisphenols (except BPS) remarkably shortened the organismal lifespan and increased age-related changes in neurons. Exposure to BPA and BPF resulted in mitochondrial abnormalities, such as reduced oxygen consumption and mitochondrial membrane potential. In contrast, the ATP levels were noticeably higher after treatment with all bisphenols. In mammalian fibroblast cells, exposure to increasing concentrations of all bisphenols (ranging from 50 µM to 500 µM) caused a severe decrease in cell viability in a dose-dependent manner. BPA increased ATP levels and decreased ROS but did not affect mitochondrial permeability transition pores (mPTP). Notably, TMBPF was the only bisphenol that caused a significant increase in mitochondrial ROS and mPTP opening. These results suggest that the potentially harmful physiological effects of BPA alternatives should be considered.

Sequential Combination of Electro-Fenton and Electrochemical Chlorination Processes for the Treatment of Anaerobically-Digested Food Wastewater.

A two-stage sequential electro-Fenton (E-Fenton) oxidation followed by electrochemical chlorination (EC) was demonstrated to concomitantly treat high concentrations of organic carbon and ammonium nitrogen (NH4+-N) in real anaerobically digested food wastewater (ADFW). The anodic Fenton process caused the rapid mineralization of phenol as a model substrate through the production of hydroxyl radical as the main oxidant. The electrochemical oxidation of NH4+ by a dimensionally stable anode (DSA) resulted in temporal concentration profiles of combined and free chlorine species that were analogous to those during the conventional breakpoint chlorination of NH4+. Together with the minimal production of nitrate, this confirmed that the conversion of NH4+ to nitrogen gas was electrochemically achievable. The monitoring of treatment performance with varying key parameters (e.g., current density, H2O2 feeding rate, pH, NaCl loading, and DSA type) led to the optimization of two component systems. The comparative evaluation of two sequentially combined systems (i.e., the E-Fenton-EC system versus the EC-E-Fenton system) using the mixture of phenol and NH4+ under the predetermined optimal conditions suggested the superiority of the E-Fenton-EC system in terms of treatment efficiency and energy consumption. Finally, the sequential E-Fenton-EC process effectively mineralized organic carbon and decomposed NH4+-N in the real ADFW without external supply of NaCl.

Curcumin attenuates adhesion molecules and matrix metalloproteinase expression in hypercholesterolemic rabbits.

Curcumin, the yellow substance found in turmeric, possesses antioxidant, anti-inflammation, anticancer, and lipid-lowering properties. Because we hypothesized that curcumin could ameliorate the development of atherosclerosis, the present study focused on the effects and potential mechanisms of curcumin consumption on high-cholesterol diet-induced atherosclerosis in rabbits. During our study, New Zealand white rabbits were fed 1 of 3 experimental diets: a normal diet, a normal diet enriched with 1% cholesterol (HCD), or an HCD supplemented with 0.2% curcumin. At the end of 8 weeks, blood samples were collected to determine the levels of serum lipids, cytokines, and soluble adhesion molecule levels. Gene expression of adhesion molecules and matrix metalloproteinases (MMPs) in aortas were measured by quantitative real-time polymerase chain reaction and Western blot. Compared with the HCD group, rabbits fed an HCD supplemented with 0.2% curcumin had significantly less aortic lesion areas and neointima thickening. Curcumin reduced the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and oxidized low-density lipoprotein cholesterol in serum by 30.7%, 41.3%, 30.4%, and 66.9% (all P < .05), respectively, but did not affect high-density lipoprotein cholesterol levels. In addition, curcumin attenuated HCD-induced CD36 expression, circulating inflammatory cytokines, and soluble adhesive molecule levels. Curcumin reduced the mRNA and protein expression of intracellular adhesion molecule-1, vascular cell adhesion molecule-1, P-selectin, and monocyte chemotactic protein-1, and it inhibited HCD-induced up-regulation of MMP-1, MMP-2, and MMP-9. Our results demonstrate that curcumin exerts an antiatherosclerotic effect, which is mediated by multiple mechanisms that include lowering serum lipids and oxidized low-density lipoprotein, thus modulating the proinflammatory cytokine levels and altering adhesion molecules and MMP gene expression.

Curcumin attenuates diet-induced hepatic steatosis by activating AMP-activated protein kinase.

Curcumin is a well-known component of traditional turmeric (Curcuma longa), which has been reported to prevent obesity and diabetes. However, the effect of curcumin on hepatic lipid metabolism remains unclear. The aim of this study was to examine the effects of curcumin on hepatic steatosis in high-fat/cholesterol diet (HFD)-induced obese mice. Male C57BL/6J mice were fed a normal diet (ND), HFD or HFD with 0.15% curcumin (HFD+C) for 11 weeks. We found that curcumin significantly lowered the body-weight and adipose tissue weight of mice in the HFD+C group compared with the findings for the HFD group (p < 0.05). The levels of total cholesterol, fasting glucose and insulin in serum were decreased, and HFD-induced impairment of insulin sensitivity was improved by curcumin supplementation (p < 0.05). Curcumin protected against the development of hepatic steatosis by reducing hepatic fat accumulation. Moreover, curcumin activated AMP-activated protein kinase (AMPK) and elevated the gene expression of peroxisome proliferator-activated receptor alpha. By contrast, curcumin suppressed the HFD-mediated increases in sterol regulatory element-binding protein-1, acetyl-CoA carboxylase 1, fatty acid synthase and cluster of differentiation 36 expression. Taken together, these findings indicate that curcumin attenuates HFD-induced hepatic steatosis by regulating hepatic lipid metabolism via AMPK activation, suggesting its use as a therapeutic for hepatic steatosis.

Abietic acid has an anti-obesity effect in mice fed a high-fat diet.

We investigated the anti-obesity effect of abietic acid in mice fed a high-fat diet with emphasis on changes in adipogenesis in epididymal adipose tissues. Male C57BL/6J mice were divided into four groups and fed a normal diet, a high-fat diet (HFD), or HFD plus oral administration of abietic acid (20 mg/kg of body weight/day [LA] or 40 mg/kg of body weight/day [HA]) for 8 weeks. Compared with the HFD group, mice orally administered 40 mg of abietic acid/kg of body weight/day exhibited significantly decreased body weight and adipose tissue weights. Serum triglyceride concentrations in the HA group were significantly lower than those in the HFD group, as were the levels of serum insulin and leptin. Hematoxylin and eosin staining revealed that epididymal adipose tissue mass was decreased by abietic acid administration. Abietic acid also inhibited the protein expression of sterol regulatory element-binding protein-1c, CCAAT/enhancer-binding protein α, and CD36 in epididymal adipose tissues, which are up-regulated by HFDs. These data demonstrate that abietic acid has an anti-obesity effect in mice mediated by the regulation of adipogenesis.