Background: Understanding of the gut-liver axis is important for the up-to-date management of liver cirrhosis, and changes of intestinal functions form the core o

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Changes of Intestinal Functions in Liver Cirrhosis

Reperfusion injury, the paradoxical tissue response that is manifested by blood flow-deprived and oxygen-starved organs following the restoration of blood flow and tissue oxygenation, has been a focus of basic and clinical research for over 4-decades. While a variety of molecular mechanisms have been proposed to explain this phenomenon, excess production of reactive oxygen species (ROS) continues to receive much attention as a critical factor in the genesis of reperfusion injury. As a consequence, considerable effort has been devoted to identifying the dominant cellular and enzymatic sources of excess ROS production following ischemia-reperfusion (I/R). Of the potential ROS sources described to date, xanthine oxidase, NADPH oxidase (Nox), mitochondria, and uncoupled nitric oxide synthase have gained a status as the most likely contributors to reperfusion-induced oxidative stress and represent priority targets for therapeutic intervention against reperfusion-induced organ dysfunction and tissue damage. Although all four enzymatic sources are present in most tissues and are likely to play some role in reperfusion injury, priority and emphasis has been given to specific ROS sources that are enriched in certain tissues, such as xanthine oxidase in the gastrointestinal tract and mitochondria in the metabolically active heart and brain. The possibility that multiple ROS sources contribute to reperfusion injury in most tissues is supported by evidence demonstrating that redox-signaling enables ROS produced by one enzymatic source (e.g., Nox) to activate and enhance ROS production by a second source (e.g., mitochondria). This review provides a synopsis of the evidence implicating ROS in reperfusion injury, the clinical implications of this phenomenon, and summarizes current understanding of the four most frequently invoked enzymatic sources of ROS production in post-ischemic tissue.

Reperfusion injury and reactive oxygen species: The evolution of a concept.

Elevated copper and oxidative stress in cancer cells as a target for cancer treatment

Spermatogenesis is an extremely active replicative process capable of generating approxi mately 1,000 sperm a second. The high rates of cell division inherent in this process imply correspondingly high rates of mitochondrial oxygen consumption by the germinal epithelium. However, the poor vascularization of the testes means that oxygen tensions in this tissue are low1 and that competition for this vital element within the testes is extremely intense. Since both spermatogenesis2 and Leydig cell steroidogenesis3,4 are vulnerable to oxidative stress, the low oxygen tension that characterizes this tissue may be an important component of the mechanisms by which the testes protects itself from free radical-mediated damage. In addition, the testes contain an elaborate array of antioxidant enzymes and free radical scavengers to ensure that the twin spermatogenic and steroidogenic functions of this organ are not impacted by oxidative stress. These antioxidant defence systems are of major importance because peroxidative damage is currently regarded as the single most important cause of impaired testicular function underpinning the pathological consequences of a wide range of conditions from testicular torsion to diabetes and xenobiotic exposure. This chapter sets out the specific nature of these antioxidant defence systems and also reviews the factors that have been found to impair their activity, precipitating a state of oxidative stress in the testes and impairing the latter’s ability to produce viable spermatozoa capable of initiating and supporting embryonic development.

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Antioxidant systems and oxidative stress in the testes.

This public health statement tells you about cadmium and the effects of exposure to it.The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for long-term federal clean-up activities. Cadmium has been found in at least 1,014 of the 1,669 current or former NPL sites. Although the total number of NPL sites evaluated for this substance is not known, the possibility exists that the number of sites at which cadmium is found may increase in the future as more sites are evaluated. This information is important because these sites may be sources of exposure and exposure to this substance may be harmful.When a substance is released either from a large area, such as an industrial plant, or from a container, such as a drum or bottle, it enters the environment. Such a release does not always lead to exposure. You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking the substance, or by skin contact.If you are exposed to cadmium or cadmium compounds, many factors will determine whether you will be harmed. These factors include the dose (how much), the duration (how long), and how you come in contact with it. You must also consider any other chemicals you are exposed to and your age, sex, diet, family traits, lifestyle, and state of health.

Toxicological Profile for Cadmium

http://if-pan.krakow.pl/pjp/pdf/2005/4_481_ab.pdf

L-carnitine inhibits ethanol-induced gastric mucosal injury in rats.

Testicular torsion is a urological emergency referred to as ‘acute scrotum’, because inappropriate treatment can lead to male subfertility and infertility. A possible cause of testicular damage is the ischaemia–reperfusion (I/R) injury attributed to oxygen free radicals. L-carnitine, a vitamin-like antioxidant, plays a pivotal role in the maturation of spermatozoa within the reproductive tract. The aim of the present paper was to determine the protective effect of L-carnitine on testicular I/R-induced injury. Thirty-two male rats were divided into 4 groups (n = 8). Testicular torsion was created by rotating the right testis 720° in a clockwise direction. Group 1: sham-operated control; group 2: ischaemia; group 3: I/R; group 4: ischaemia–L-carnitine treatment–reperfusion group. L-carnitine (500 mg kg−1, intraperitoneally) was administered before 30 min of detorsion in Group 4. After torsion (5 h) and detorsion (5 h), bilateral orchidectomy was performed. The malondialdehyde (MDA) level was evaluated in testes. Histopathologically, Johnsen's spermatogenesis criteria and mean seminiferous tubule diameter (MSTD) measurements were used. Testicular MDA levels were higher in the torsion group compared to the sham-control group (p < 0.05). Detorsion (reperfusion) caused a further increase in MDA levels (p < 0.05). Pretreatment with L-carnitine prevented a further increase in MDA levels (p < 0.05). Histologically, torsion caused some separation among germinal cells in the seminiferous tubules, which became much more prominent in the I/R group but was attenuated with L-carnitine pretreatment. In conclusion, L-carnitine pretreatment may have a protective effect in experimental testicular torsion–detorsion model in rats by its well-known antioxidant potential. Copyright © 2006 John Wiley & Sons, Ltd.

Protective effect of L-carnitine on testicular ischaemia–reperfusion injury in rats

1. Muscle injury (rhabdomyolysis) is one of the causes of acute renal failure (ARF). Iron, free radicals and nitric oxide (NO) play a critical role in the pathogenesis of glycerol-induced myoglobinuric ARF. L-Carnitine is an anti-oxidant and prevents the accumulation of end-products of lipid peroxidation. Therefore, the aim of the present study was to investigate the effects of L-carnitine on myoglobinuric ARF induced by intramuscular (i.m.) hypertonic glycerol injection. 2. Sprague-Dawley rats were divided into three groups. Rats in group 1 (n = 8) were given saline, whereas those in groups 2 (n = 10) and 3 (n = 10) were injected with glycerol (10 mL/kg, i.m.). Concomitant with and 24 h after glycerol injection, L-carnitine (200 mg/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues were taken from anaesthetised rats. 3. Plasma creatine kinase (CK) activity, urea, creatinine and NO levels, as well as kidney tissue superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme activity and malondialdehyde (MDA) and glutathione (GSH) levels, were determined. In the kidney tissue, histopathological changes and iron accumulation in the tubular epithelium were also investigated. 4. Glycerol treatment caused severe ARF: a marked renal oxidative stress, significantly increased CK activity, urea and creatinine levels and decreased plasma NO levels. Histopathological findings in group 2 rats confirmed that there was renal impairment by cast formation and tubular necrosis and a marked increase in iron accumulation in the tubular epithelium. All these factors were significantly improved by L-carnitine supplementation. 5. These results may indicate that L-carnitine treatment protects against functional, biochemical and morphological damage and iron accumulation in glycerol-induced myoglobinuric ARF in rats. In this model, the protective effect of L-carnitine treatment may provide a new insight into the treatment of rhabdomyolysis-related ARF.

Protective effects of L-carnitine on myoglobinuric acute renal failure in rats.

Protective effects of L-carnitine and alpha-lipoic acid in rats with adjuvant arthritis.

The aim of this study was to investigate the protective effect of ibuprofen on testicular torsion/detorsion-induced ischemia/reperfusion (I/R) injury. A total of 48 prepubertal male Wistar albino rats were divided into two models: early and late orchiectomy. Testicular torsion was created by rotating the right testis 720 degrees in a clockwise direction. The ischemia period was 5 h and orchiectomy was performed after 5 h of detorsion in the early orchiectomy model (EOM). In the late orchiectomy model (LOM), the ischemia period was 5 h and orchiectomy was performed after 7 days of detorsion. In the EOM, ibuprofen (70 mg/kg, po) was administrated only once, 40 min prior to detorsion. In the LOM, ibuprofen (70 mg/kg, po) was administered 40 min before detorsion, once daily for 7 days. Bilateral orchiectomy was performed in all groups to measure the tissue levels of malondialdehyde (MDA) and to microscopically investigate light and electrons. The presence of endothelial nitric oxide synthase (eNOS) activity was shown with immunohistochemical studies. Spermatogenesis and mean seminiferous tubule diameter (MSTD) were significantly decreased in ipsilateral and contralateral testis when both early and late I/R groups were compared to the sham groups. Furthermore, ibuprofen-treated animals showed an improved histological appearance in both models of testicular torsion. Ibuprofen treatment prevented lipid peroxidation resulting in decreased MDA accumulation in the testes of both models. After I/R, eNOS immunoreactivity was increased in the testicular tissues. Ibuprofen treatment decreased eNOS immunoreactivity in the germ cells of the tubules in the contralateral testes, but intense eNOS immunoreactivity was shown in the ipsilateral testes of the LOM. Electron microscopy of the testes of rats demonstrated that ibuprofen pretreatment was particularly effective in preventing the mitochondrial degeneration in both Sertoli and spermatid cells in the LOM. Because of its anti-inflammatory and antioxidant effects, ibuprofen pretreatment may have protective effects in the experimental testicular torsion/detorsion model in rats.

Nurettin Aydogdu

Papers

L-carnitine inhibits ethanol-induced gastric mucosal injury in rats.

Protective effect of L-carnitine on testicular ischaemia–reperfusion injury in rats

Protective effects of L-carnitine on myoglobinuric acute renal failure in rats.

Protective effects of L-carnitine and alpha-lipoic acid in rats with adjuvant arthritis.

Protective effects of ibuprofen on testicular torsion/detorsion-induced ischemia/reperfusion injury in rats.