Remote preconditioning by aortic constriction: affords cardioprotection as classical or other remote ischemic preconditioning? Role of iNOS

Dose remote preconditioning by aortic constriction (RPAC) affords cardioprotection similar to classical or other remote ischemic preconditioning stimulus? Moreover study was also designed to investigate role of inducible nitric oxide synthase in remote preconditioning by aortic constriction. There are sufficient evidences that "ischemic preconditioning" has surgical applications and afford clinically relevant cardioprotection. Transient occlusion of circumflex artery, renal artery, limb artery or mesenteric artery preconditions the myocardium against ischemia reperfusion injury in case of ischemic heart disease leading to myocardial infraction. Here abdominal aorta was selected to produce RPAC. Four episodes of Ischemia-reperfusion of 5 min each to abdominal aorta produced RPAC by assessment of infract size, LDH and CK. These studies suggest RPAC produced acute (FWOP) and delayed (SWOP) cardioprotective effect. RPAC demonstrated a significant decrease in Ischemia-reperfusion induced release of LDH, CK and extent of myocardial infract size. L-NAME (10 mg/Kg i.v.), Aminoguanidine (150 mg/Kg s.c.), Aminoguanidine (300 mg/Kg s.c.), S-methyl isothiourea (3 mg/Kg i.v.), 1400W (1 mg/Kg i.v.) administered 10 min. before global ischemia reperfusion produced no marked effect. Aminoguanidine (150 mg/Kg s.c.), Aminoguanidine (300 mg/Kg s.c.), S-methyl isothiourea (3 mg/Kg i.v.), 1400W (1 mg/Kg i.v.) pretreatment after RPAC produced no significant effect on acute RPAC induced decrease in LDH, CK and infract size, whereas L-NAME (10 mg/Kg i.v.) increased RPAC induced decrease in LDH, CK and infract size. Most interesting observation is in delayed RPAC, where all NOS inhibitors pretreatment attenuate RPAC induced decrease in LDH, CK and infract size. In conclusions, "Remote preconditioning by aortic constriction" (RPAC) affords cardioprotection similar to classical or other remote ischemic preconditioning stimulus. Moreover, late or delayed phase of RPAC has been mediated by inducible nitric oxide synthase (iNOS) whereas it has not involved in acute RPAC

Explorative investigation of the anti-glycative effect of a rapeseed by-product extract

Formation of Advanced Glycation End-products (AGEs) in biological systems are increased during hyperglycaemia due to higher levels of circulating glucose, as well as carbonyl reactive species. AGEs are causative factors of common chronic diseases. Since synthetic AGE-inhibitors exert unwanted side effects and polyphenols act as potent antiglycative agents, vegetables (fruits, seeds and related by-products) are good candidates for searching natural inhibitors. The aim of this research is to explore the suitability of a polyphenol-rich rapeseed cake extract (RCext) to decrease the formation of AGEs in an in vitro model. Total Phenolic Content, antioxidant, anti-glycative activity, specific inhibition of AGEs (pentosidine and argypyrimidine), and methylglyoxal trapping capacity of the RCext were evaluated. The metabolomic profile of the extract was also analysed through GC-MS. Different phenols, amino acids, carbohydrates, organic acids and fatty acids are identified in the RCE by GC-MS. Results confirm the high concentration of polyphenols correlated with the antioxidant capacity and anti-glycative activity in a dose dependent manner. Rapeseed cake extract (3.7 mg mL−1) significantly reduced the formation of free fluorescent AGEs and pentosidine up to 34.85%. The anti-glycative activity of the extract is likely to be due to the high concentration of sinapinic acid in its metabolic profile, and the mechanism of action is mediated by methylglyoxal trapping. Results show a promising potential for using rapeseed cake extract as a food supplement to ameliorate the formation of AGEs. Rapeseed cake extract should therefore be considered a potential candidate for the prevention of glycation-associated complications of age-related pathologie

Granuloma pouch and skin histamine of the rat

Using the granuloma pouch technique of SELYE, effect of modification in local histamine on the inflammatory tissue reactions was examined in rats. The increase in the weight of pouch wall and histological inflammatory changes were distinctly inhibited in either case of histamine depletion by sinomenine and of desensitization to histamine by repeated injections of histamine. In rats injected with aminoguanidine, the skin and local histamine contents increased in similar degree as those in rats receiving histamine injection, but the inflammatory tissue reactions were severer than in the control. The total histamine of the pouch wall during inflammation reached the maximum four days after the injection of croton oil and decreased thereaftcr. The prcliferative processes indicating the recovery of injured tissues in later stages of the inflammation were the most vigorous in rats treated with histamine and this was in contrast to the extreme weakness of this tendency in animals in which the local histamine had been depleted. These observations not only suggests the fairly close relationship of histamine to carly reaction of inflammation but also indicates the role of histamine in its recovery processes.</p

Prevention of Protein Glycation by Natural Compounds

Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, especially polyphenols and other natural antioxidants. Extrapolation of results of in vitro studies on the in vivo situation is not straightforward due to differences in the conditions and mechanism of glycation, and bioavailability problems. Nevertheless, available data allow to postulate that enrichment of diet in natural anti-glycating agents may attenuate glycation and, in consequence, ageing

Immune modulation by fish kinetoplastid parasites : a role for nitric oxide

Trypanoplasma borreli and Trypanosoma carassii are kinetoplastid parasites infecting cyprinid fish. We investigated the role of nitric oxide (NO) in immune modulation during T. borreli and T. carassii infection of carp. Phagocytic cells from different organs produced NO and serum nitrate levels increased, demonstrating that T. borreli activates NO production in vivo. In contrast, T. carassii did not induce NO production in vivo and inhibited LPS-induced NO production in vitro. Production of NO was detrimental to the host as T. borreli-infected carp treated with the inducible NO synthase inhibitor aminoguanidine had a higher survival than infected control carp. This detrimental effect can be explained (in part) by the toxicity of NO to cells in vitro as NO inhibited the proliferative response of blood and spleen leukocytes. Head-kidney phagocytes were resistant to the immunosuppressive effects of NO in vitro. The NO-inducing activity of T. borreli may be an adaptation developed to ensure survival and immune evasion in the fish host. Apparently, T. carassii has adopted another strategy by deactivating specific functions of phagocytes. Both strategies may ensure long-term survival of the parasite

Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance

Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems—imidazopurinones. The adduct derived from methylglyoxal-3-(2′-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers—was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2′-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity

Pharmacologic approaches against advanced glycation end products (ages) in diabetic cardiovascular disease

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports

Potential role of NADPH-oxidase in early steps of lead-induced oxidative burst in Vicia faba roots

The mechanism of oxidative burst induced by lead in Vicia faba excised roots was investigated by luminol-dependent chemiluminescence. Results showed that lead triggered a rapid and dose-dependent increase in chemiluminescence production. In this study, specific inhibitors of putative reactive oxygen species (ROS) sources were used to determine the mechanism of lead-induced ROS generation. This generation was sensitive to dephenylene iodonium (DPI), quinacrine and imidazole, some inhibitors of the NADPH-oxidase and not inhibited by other putative ROS sources inhibitors. Data reported in this work clearly demonstrated the pivotal role of NADPH-oxidase-like enzyme in early steps of lead-induced oxidative burst. To investigate the respective implication of calmodulin and protein kinase (PK) in leadinduced NADPH-oxidase activation, excised roots were treated with the calmodulin inhibitor W7 or with the PK inhibitor staurosporine. The chemiluminescence generation inhibition by these inhibitors illustrated the role of PK in lead-induced NADPH-oxidase activation and revealed a calmodulin-dependent step. Using the calcium entry blocker La 3+ or different concentrations of calcium in the extracellular medium, our data highlighted the implication of Ca 2+ channel in leadinduced oxidative burst

Viral-induced neurodegenerative disease.

Viral etiology has been postulated in a variety of neurological diseases in humans, including multiple sclerosis. Several experimental animal models of viral-induced neurodegenerative disease provide insight into potential host- and pathogen-dependent mechanisms involved in the disease process. Two such mouse models are the Theiler's murine encephalomyelitis virus (TMEV) infection and mouse hepatitis virus (MHV) infection

Oxidative stress, protein glycation and nutrition – interactions relevant to health and disease throughout the lifecycle

Protein glycation has been studied for over a century now and plays an important role in disease pathogenesis throughout the lifecycle. Strongly related to diabetic complications, glycation of Hb has become the gold standard method for diabetes diagnosis and monitoring. It is however attracting attention in normoglycaemia as well lately. Longitudinal studies increasingly suggest a positive relationship between glycation and the risk of chronic diseases in normoglycaemic individuals, but the mechanisms behind this association remain unclear. The interaction between glycation and oxidative stress may be particularly relevant in the normoglycaemic context, as suggested by recent epidemiological and in vitro evidence. In that context nutritional and lifestyle factors with an influence on redox status, such as smoking, fruit and vegetable and antioxidants consumption, may have the capacity to promote or inhibit glycation. However, experimental data from controlled trials are lacking the quality and rigour needed to reach firm conclusions. In the present review, we discuss the importance of glycation for health through the lifecycle and focus on the importance of oxidative stress as a driver for glycation. The importance of nutrition to modulate glycation is discussed, based on the evidence available and recommendations towards higher quality future research are made