Oxidative Medicine and Cellular Longevity

Quá trình oxi hóa lipid có thể được mô tả chung là một quá trình mà các chất oxi hóa như các gốc tự do tấn công các lipid có chứa liên kết đôi carbon-carbon, đặc biệt là các axit béo không bão hòa đa (PUFAs). Trong bốn thập kỷ qua, một lượng lớn tư liệu về quá trình oxi hóa lipid đã cho thấy vai trò quan trọng của nó trong sinh học tế bào và sức khỏe con người. Từ đầu những năm 1970, tổng số bài báo nghiên cứu được công bố về chủ đề oxi hóa lipid chỉ là 98 (1970–1974) và đã tăng gần 135 lần, lên tới 13165 trong 4 năm qua (2010–2013). Những phát hiện mới về sự tham gia vào sinh lý và bệnh lý tế bào, cũng như việc kiểm soát quá trình oxi hóa lipid, tiếp tục xuất hiện mỗi ngày. Với sự rộng lớn của lĩnh vực này, bài tổng quan này tập trung vào các khái niệm hóa sinh của quá trình oxi hóa lipid, sản sinh, chuyển hóa, và cơ chế tín hiệu của hai sản phẩm oxi hóa lipid thuộc nhóm axit béo omega-6 chính: malondialdehyde (MDA) và đặc biệt là 4-hydroxy-2-nonenal (4-HNE), tổng hợp không chỉ về chức năng sinh lý và bảo vệ của nó như một phân tử tín hiệu kích thích sự biểu hiện gen và sự sống sót của tế bào, mà còn vai trò gây độc tế bào của nó khi ức chế biểu hiện gen và thúc đẩy cái chết tế bào. Cuối cùng, các tổng quan về các hệ thống mô hình động vật có vú in vivo được sử dụng để nghiên cứu quá trình oxi hóa lipid và các quy trình bệnh lý phổ biến liên quan đến MDA và 4-HNE được trình bày.

Polyphenol là các chất chuyển hóa thứ cấp của thực vật và thường tham gia vào việc bảo vệ chống lại tia cực tím hoặc sự xâm nhập của các tác nhân gây bệnh. Trong thập kỷ qua, đã có nhiều quan tâm về tiềm năng lợi ích sức khỏe từ polyphenol thực vật trong chế độ ăn uống như một chất chống oxy hoá. Các nghiên cứu dịch tễ học và phân tích tổng hợp liên quan mạnh mẽ đến việc tiêu thụ lâu dài các chế độ ăn uống giàu polyphenol thực vật có thể cung cấp sự bảo vệ chống lại sự phát triển của ung thư, bệnh tim mạch, tiểu đường, loãng xương và các bệnh thoái hóa thần kinh. Tại đây, chúng tôi trình bày kiến thức về các tác động sinh học của polyphenol thực vật trong bối cảnh liên quan đến sức khỏe con người.

The balance between oxidation and antioxidation is believed to be critical in maintaining healthy biological systems. Under physiological conditions, the human antioxidative defense system including e.g., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and others, allows the elimination of excess reactive oxygen species (ROS) including, among others superoxide anions (O₂^.-), hydroxyl radicals (OH^.), alkoxyl radicals (RO^.) and peroxyradicals (ROO^.). However, our endogenous antioxidant defense systems are incomplete without exogenous originating reducing compounds such as vitamin C, vitamin E, carotenoids and polyphenols, playing an essential role in many antioxidant mechanisms in living organisms. Therefore, there is continuous demand for exogenous antioxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated compounds may be toxic, owing to prooxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. This review aims to examine the double‐edged effects of dietary originating antioxidants with a focus on the most abundant compounds, especially polyphenols, vitamin C, vitamin E and carotenoids. Different approaches to enrich our body with exogenous antioxidants such as via synthetic antioxidants, diets rich in fruits and vegetables and taking supplements will be reviewed and experimental and epidemiological evidences discussed, highlighting that antioxidants at physiological doses are generally safe, exhibiting interesting health beneficial effects.

Background. There are several health benefits that honeybee products such as honey, propolis, and royal jelly claim toward various types of diseases in addition to being food. Scope and Approach. In this paper, the effects of honey, propolis, and royal jelly on different metabolic diseases, cancers, and other diseases have been reviewed. The modes of actions of these products have also been illustrated for purposes of better understanding. Key Findings and Conclusions. An overview of honey, propolis, and royal jelly and their biological potentials was highlighted. The potential health benefits of honey, such as microbial inhibition, wound healing, and its effects on other diseases, are described. Propolis has been reported to have various health benefits related to gastrointestinal disorders, allergies, and gynecological, oral, and dermatological problems. Royal jelly is well known for its protective effects on reproductive health, neurodegenerative disorders, wound healing, and aging. Nevertheless, the exact mechanisms of action of honey, propolis, and royal jelly on the abovementioned diseases and activities have not been not fully elucidated, and further research is warranted to explain their exact contributions.

Reactive oxygen species (ROS) are by-products of normal cell activity. They are produced in many cellular compartments and play a major role in signaling pathways. Overproduction of ROS is associated with the development of various human diseases (including cancer, cardiovascular, neurodegenerative, and metabolic disorders), inflammation, and aging. Tumors continuously generate ROS at increased levels that have a dual role in their development. Oxidative stress can promote tumor initiation, progression, and resistance to therapy through DNA damage, leading to the accumulation of mutations and genome instability, as well as reprogramming cell metabolism and signaling. On the contrary, elevated ROS levels can induce tumor cell death. This review covers the current data on the mechanisms of ROS generation and existing antioxidant systems balancing the redox state in mammalian cells that can also be related to tumors.

Increasing interest has recently focused on determining whether several natural compounds, collectively referred to as nutraceuticals, may exert neuroprotective actions in the developing, adult, and aging nervous system. Quercetin, a polyphenol widely present in nature, has received the most attention in this regard. Several studies in vitro, in experimental animals and in humans, have provided supportive evidence for neuroprotective effects of quercetin, either against neurotoxic chemicals or in various models of neuronal injury and neurodegenerative diseases. The exact mechanisms of such protective effects remain elusive, though many hypotheses have been formulated. In addition to a possible direct antioxidant effect, quercetin may also act by stimulating cellular defenses against oxidative stress. Two such pathways include the induction of Nrf2‐ARE and induction of the antioxidant/anti‐inflammatory enzyme paraoxonase 2 (PON2). In addition, quercetin has been shown to activate sirtuins (SIRT1), to induce autophagy, and to act as a phytoestrogen, all mechanisms by which quercetin may provide its neuroprotection.

Manganese (Mn) is an essential element that is involved in the synthesis and activation of many enzymes and in the regulation of the metabolism of glucose and lipids in humans. In addition, Mn is one of the required components for Mn superoxide dismutase (MnSOD) that is mainly responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress. Both Mn deficiency and intoxication are associated with adverse metabolic and neuropsychiatric effects. Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus (T2MD), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis, has increased dramatically. Previous studies have found that ROS generation, oxidative stress, and inflammation are critical for the pathogenesis of metabolic diseases. In addition, deficiency in dietary Mn as well as excessive Mn exposure could increase ROS generation and result in further oxidative stress. However, the relationship between Mn and metabolic diseases is not clear. In this review, we provide insights into the role Mn plays in the prevention and development of metabolic diseases.

About 246 million people worldwide had diabetes in 2007. The global figure of people with diabetes is projected to increase to 370 million in 2030. As the prevalence of diabetes has risen to epidemic proportions worldwide, diabetic nephropathy has become one of the most challenging health problems. Therapeutic options such as strict blood glucose and blood pressure controls are effective for preventing diabetic nephropathy, but are far from satisfactory, and the number of diabetic patients on end‐stage renal disease is still increasing. Therefore, a novel therapeutic strategy that could halt the progression of diabetic nephropathy should be developed. There is accumulating evidence that advanced glycation end products (AGEs), senescent macroprotein derivatives formed at an accelerated rate under diabetes, play a role in diabetic nephropathy via oxidative stress generation. In this paper, we review the pathophysiological role of AGEs and their receptor (RAGE)‐oxidative stress system in diabetic nephropathy.

Reactive oxygen species (ROS) are cytotoxic agents that lead to significant oxidative damage. Bisphenol A (BPA) is a contaminant with increasing exposure to it and exerts both toxic and estrogenic effects on mammalian cells. Due to limited information concerning the effect of BPA on liver, this study investigates whether BPA causes hepatotoxicity by induction of oxidative stress in liver. Rats were divided into five groups: The first four groups, BPA (0.1, 1, 10, 50 mg/kg/day) were administrated orally to rats for four weeks. The fifth group was taken water with vehicle. The final body weights in the 0.1 mg group showed a significant decrease compared to control group. Significant decreased levels of reduced glutathione, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and catalase activity were found in the 50 mg BPA group compared to control groups. High dose of BPA (50 mg/kg) significantly increased the biochemical levels of ALT, ALP and total bilirubin. BPA effect on the activity of antioxidant genes was confirmed by real time PCR in which the expression levels of these genes in liver tissue were significantly decrease compared to control. Data from this study demonstrate that BPA generate ROS and reduce the antioxidant gene expression that causes hepatotoxicity.