다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys

As technology continues to advance, heavy metals in drinking water have exceeded recommended limits from regulators around the world. The main source of human exposure to heavy metals is from contaminated drinking water. The effects of drinking water contaminated with heavy metals, such as arsenic, lead, nickel, cadmium and mercury, have gradually caught the attention of the relevant departments and personnel. It is well known that occupational exposure to heavy metals occurs as a result of using these metals in a variety of industrial processes in and/or a variety of materials, including color pigments and alloys. A series of adverse effects on human metabolism has resulted from exposure to heavy metal-contaminated drinking water, which has been recorded from around the world. The general mechanism of heavy metal toxicity is through the production of reactive oxygen species, the appearance of oxidative damage, and subsequent adverse effects on health. Therefore, water contaminated with heavy metals causes high morbidity and mortality worldwide. In order to address concern regarding the health effects of different heavy metals, this paper reviews its sources, distribution and effects of heavy metal on human metabolism.HIGHLIGHTSThe accumulation of heavy metals such as lead, arsenic, mercury, cadmium and nickel will destroy the main metabolic process of human body.Redox reactions in biological systems are caused by carcinogenic metal ions such as nickel and arsenic. The free radicals produced by these reactions cause oxidative damage to proteins and DNA.The accumulation of heavy metals eventually produces reactive oxygen species that can cause oxidative stress, which may lead to the production of various diseases.

The effects of heavy metals on human metabolism.

Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol–disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol–disulfide redox systems. In particular, central principles have emerged concerning redox comp...

/pdf/thiol-disulfide-redox-states-in-signaling-and-sensing-2izklk3mip.pdf

Thiol/disulfide redox states in signaling and sensing

Interplay of calcium and cadmium in mediating cadmium toxicity.

Lead acetate (300 mg/L) and/or cadmium chloride (50 mg/L) were administered as drinking water to Sprague-Dawley rats for 8 weeks to investigate the possible combined effects of these metals on the damage in renal cortex mitochondria. Increased malonaldehyde levels due to exposure to these metals were detected by colorimetric method, which demonstrated the lipid peroxidation in the renal cortex. Ultrastructural observations and real-time quantitative PCR analyses were performed on kidney cortex pieces to identify the mitochondrial damage and quantify the relative expression levels of cytochrome oxidase subunits (COX-I/II/III), respectively. The most striking ultrastructural modifications involved distortion of mitochondrial cristae and an unusual arrangement, which were more evident when the mixture was ingested. There were significant differences in the expression levels of COX-I, II, and III between the control group and the exposed groups, whereas those in the (lead+cadmium) group were all significantly lower than that in the lead or cadmium group. In conclusion, there was an obvious synergistic oxidative damage effect of lead combined with cadmium on rat kidney cortex mitochondria, which increased defects in mitochondrial oxidative metabolism.

Effects of lead and/or cadmium on the oxidative damage of rat kidney cortex mitochondria.

The combined effects of lead (Pb) and cadmium (Cd) on primary cultures of rat proximal tubular (rPT) cells were studied. These cells were either treated with Pb acetate (0.5 and 1 μM) alone, Cd acetate (2.5 and 5 μM) alone, or a combination of Pb and Cd acetate, and then joint cytotoxicity was evaluated. The results showed that the combination of these two metals decreased cell viability and increased the number of apoptotic and necrotic cells and lactate dehydrogenase release synergistically. Simultaneously, increased intracellular reactive oxygen species, malondialdehyde, and calcium levels and decreased mitochondrial membrane potential, intracellular acidification, and inhibition of Na+, K+-, and Ca2+-ATPase activities were shown during the exposure. In addition, apoptotic morphological changes induced by these treatments in rPT cells were demonstrated by Hoechst 33258 staining. The apoptosis was markedly prevented by N-acetyl-l-cysteine, whereas necrosis was not affected. In summary, there was a synergistic cytototic effect of Pb combined with Cd on rPT cells. Cell death induced by Pb–Cd mixture was mediated by an apoptotic and a necrotic mechanism. Apoptotic death was the chief mechanism. Changes of intracellular events were intimately correlated with both oxidative stress and mitochondrial dysfunction, which promoted the development of apoptosis.

Simultaneous Effects of Lead and Cadmium on Primary Cultures of Rat Proximal Tubular Cells: Interaction of Apoptosis and Oxidative Stress

Artemisinin and Artemisia annua leaves alleviate Eimeria tenella infection by facilitating apoptosis of host cells and suppressing inflammatory response.

There are very few reports on the protective effect of artesunate (ARS) in ulcerative colitis (UC). This study focused on the efficacy of ARS on intestinal barrier, inflammatory response, and potential mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. The results suggested that ARS treatment markedly alleviated DSS-induced clinical symptoms by relieving body weight loss, the disease activity index (DAI) score, and preventing colonic shortening. HE staining and scanning electron microscope analysis revealed that ARS treatment significantly protected the integrity of intestinal barrier through alleviating DSS-induced erosion of surface epithelial cells, reduction of goblet cells, and destruction of the crypt accompanied with inflammatory cells infiltration. Immunofluorescence histochemical staining and western blot assay confirmed that ARS notably inhibited the loss of Muc2 and claudin-1 in mucosal layer with a relative higher level of Bcl-2/Bax ratio and, moreover, inhibited cleaved-caspase-3 expression in colon tissue. In addition, this study reconfirmed the anti-inflammatory function of ARS evidenced by remarkably suppressing the phosphorylation of nuclear factor-κBα (IκBα) and NF-κB p65 and the expression of IL-1β, IL-6, and TNF-α while enhancing IL-10 expression. Taken together, these data highlight that ARS has the protective effect on UC through maintaining the expression of intestinal mucosal barrier-related proteins, suppressing the apoptosis and inflammatory response. This study may facilitate to understand the action mechanism of ARS against UC.

Artesunate ameliorates DSS-induced ulcerative colitis by protecting intestinal barrier and inhibiting inflammatory response.

In our previous study, lipopolysaccharide (LPS) significantly reduced the cell viability of primary bovine mammary epithelial cells (bMEC) leading to cell apoptosis, which were prevented by caffeic acid (CA) through inhibiting NF-κB activation and reducing proinflammatory cytokine expression. While the underlying mechanism remains unclear, here, we determined that LPS induced the extensive microstructural damage of bMEC, especially the mitochondria and endoplasmic reticulum. Then, the obvious reduction of mitochondrial membrane potential and expression changes of apoptosis-associated proteins (Bcl-2, Bax, and casepase-3) indicated that apoptosis signaling through the mitochondria should be responsible for the cell viability decrease. Next, the high-throughput cDNA sequencing (RNA-Seq) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were employed to verify that the MAPK and JAK-STAT signaling pathways also were the principal targets of LPS. Following, the critical proteins (ERK, JNK, p38, and c-jun) of the MAPK signaling pathways were activated, and the release of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-8) regulated by NF-κB and MAPKs was significantly increased, which can promote a cascade of inflammation that induces cell injury and apoptosis. Meanwhile, CA significantly inhibited the activation of MAPKs and the release of proinflammatory cytokines in a dose-dependent manner, which were similar to its effects on the NF-κB activation that we previously published. So we concluded that CA regulates the proteins located in the upstream of multiple cell signal pathways which can reduce the LPS-induced activation of NF-κB and MAPKs, thus weakening the inflammatory response and maintaining cell structure and function, which accordingly inhibit apoptosis.

/pdf/caffeic-acid-prevented-lps-induced-injury-of-primary-bovine-4cc38je3b6.pdf

Jingui Li

Papers

Effects of lead and/or cadmium on the oxidative damage of rat kidney cortex mitochondria.

Simultaneous Effects of Lead and Cadmium on Primary Cultures of Rat Proximal Tubular Cells: Interaction of Apoptosis and Oxidative Stress

Artemisinin and Artemisia annua leaves alleviate Eimeria tenella infection by facilitating apoptosis of host cells and suppressing inflammatory response.

Artesunate ameliorates DSS-induced ulcerative colitis by protecting intestinal barrier and inhibiting inflammatory response.

Caffeic Acid Prevented LPS-Induced Injury of Primary Bovine Mammary Epithelial Cells through Inhibiting NF-κB and MAPK Activation