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Qing-Shuo Zhang, Weiliang Tang, Matthew Deater, Ngoc Phan, Andrea N Marcogliese, Hui Li, Muhsen Al-Dhalimy, Angela Major, Susan Olson, Raymond J Monnat, Markus Grompe
Fanconi anemia is an inherited bone marrow failure disorder associated with a high incidence of leukemia and solid tumors. Bone marrow transplantation is currently the only curative therapy for the hematopoietic complications of this disorder. However, long-term morbidity and mortality remain very high and new therapeutics are badly needed. Here we show that the widely used diabetes drug metformin improves hematopoiesis and delays tumor formation in Fancd2(-/-) mice. Metformin is the first compound reported to improve both of these Fanconi anemia phenotypes...
October 18, 2016: Blood
Manuel Luis Wolfson, Julieta Aisemberg, Fernando Correa, Ana María Franchi
BACKGROUND AND PURPOSE: Maternal infections with Gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue play an important role on the establishment of a local inflammatory process that result in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss...
October 12, 2016: Journal of Cellular Physiology
Lourdes Dias, Mariana A P Rodrigues, Bruna R Inoue, Renata L Rodrigues, André L Rennó, Valéria B de Souza, Frank D Torres-Huaco, Norma C Sousa, Alessandra Stroka, Anibal R Melgarejo, Stephen Hyslop
In this work, we examined some mechanisms involved in the hypotension caused by Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and gradually returned to baseline over 60 min. Pretreatment of rats with the non-selective nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) did not attenuate the early phase of venom-induced hypotension, but abolished the recovery phase and resulted in rapid death; a similar effect was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ...
October 5, 2016: Toxicon: Official Journal of the International Society on Toxinology
Елена В Хмиль, Лилия И Ляшенко, Наталия В Янко, Дмитрий А Хмиль, Людмила Ф Каськова
INTRODUCTION: one of the peroxidation stress mechanisms is inducible NO synthase (iNOS) expression involved in the pathogenesis of periodontitis. AIM: to access the influence of isoform NO synthase (NOS) on alteration mechanisms of oxidative stress at periodontal tissues of 50 mature rats in a simulated periodontitis (SP). MATERIALS AND METHODS: a SP at rats was induced by a high-carbohydrate, high-fat (HCHF) diet. Тreated SP rat groups were intragastrically administered with selective neuronal NOS (nNOS) inhibitor 7-nitroindazole, selective inducible NOS (iNOS) inhibitor aminoguanidine, and nitric oxide synthase substrate L-arginine...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Алексей В Богданов, Юлия М Гришко, Виталий А Костенко
INTRODUCTION: intake of inorganic nitrates is typically accompanied by production of excessive amount of nitric oxide (NO), which level is maintained by the mechanism of autoregulation known as the NO cycle. Hypothetically, this process may be disrupted with fluorides that are able to suppress arginase pathway of L-arginine metabolism, which competes with NO-synthase pathway. AIM: to study mechanisms of disregulation of oxidative (NO-synthase) and non-oxidative (arginase) metabolic pathways of L-arginine in the tissues of periodontium under combined excessive sodium nitrate and fluoride intake...
2016: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Ik-Soo Lee, Yu Jin Kim, Seung-Hyun Jung, Joo-Hwan Kim, Jin Sook Kim
In our ongoing efforts to identify effective naturally sourced agents for the treating of diabetic complications, two new (1 and 2) and 11 known phenolic compounds (3-13) were isolated from an 80 % ethanol extract of Litsea japonica leaves. The structures of the new compounds were established by spectroscopic and chemical studies. These isolates (1-13) were subjected to an in vitro bioassay evaluating their inhibitory activity on advanced glycation end products formation and rat lens aldose reductase activity...
September 30, 2016: Planta Medica
Ewa Grzebyk, Agnieszka Piwowar
BACKGROUND: Advanced glycation endproducts (AGE) and advanced oxidation protein products (AOPP) arise as a result of excessive glycation and oxidation processes of proteins in hyperglycemia and oxidative stress conditions respectively, both in vivo and in vitro. In vivo these processes are especially intensified in patients with diabetes, and the adverse effects of AGE and AOPP are particularly unfavorable for the pathogenesis and aggravate the biochemical disturbances and clinical complications of diabetes...
September 29, 2016: BMC Complementary and Alternative Medicine
Christopher E Malmberg, Stephen Chamberland
The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued...
2016: Journal of Visualized Experiments: JoVE
Adnan Amin, Emmy Tuenter, Paul Cos, Louis Maes, Vassiliki Exarchou, Sandra Apers, Luc Pieters
The exudate of Ferula narthex Boiss. (Apiaceae) is widely used in the Indian subcontinent as a spice and because of its health effects. Six sesquiterpene coumarins have been isolated from this exudate: feselol, ligupersin A, asacoumarin A, 8'-O-acetyl-asacoumarin A, 10'R-karatavacinol and 10'R-acetyl-karatavacinol. Based on its use in infectious and diabetic conditions, the isolated constituents were evaluated for antimicrobial and antiglycation activities. Some compounds showed activity against protozoal parasites, asacoumarin A being the most active one against Plasmodium falciparum K1 (IC50 1...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Seung Hwan Hwang, Zhiqiang Wang, Ha Na Yoon, Soon Sung Lim
Phytochemical investigation of the natural products from Xanthium strumarium led to the isolation of fourteen compounds including seven caffeoylquinic acid (CQA) derivatives. The individual compounds were screened for inhibition of α-glucosidase, protein tyrosine phosphatase 1β (PTP1β), advanced glycation end products (AGEs), and ABTS⁺ radical scavenging activity using in vitro assays. Among the isolated compounds, methyl-3,5-di-caffeoyquinic acid exhibited significant inhibitory activity against α-glucosidase (18...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hanna Müller, Christel Weiss, Marcus Renner, Ursula Felderhoff-Müser, Jan Mollenhauer
Meconium aspiration syndrome (MAS) is characterized by surfactant inactivation and inflammation. As lung epithelial cells up-regulate nitric oxide (NO) in response to inflammation, the NO production following meconium exposition was examined in relation to expression of Deleted in Malignant Brain Tumors 1 (DMBT1), a protein with functions in innate immunity and inflammatory regulation. Here, DMBT1 expression was analyzed by immunohistochemistry in postmortem lung sections from patients with MAS. The lung epithelial cell line A549, stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty expression plasmid (DMBT1- cells), was exposed to meconium...
September 15, 2016: Histochemistry and Cell Biology
Rajesh G Mishra, Tzu-Ling Tseng, Mei-Fang Chen, Po-Yi Chen, Tony J-F Lee
Nitric oxide (NO) overproduction via induction of inducible nitric oxide synthase (iNOS) is implicated in vasodilatory shock in sepsis, leading to septic encephalopathy and accelerating cerebral ischemic injury. An abbreviated urea-cycle (L-citrulline-L-arginine-NO cycle) has been demonstrated in cerebral perivascular nitrergic nerves and endothelial cells but not in normal cerebral vascular smooth muscle cell (CVSMC). This cycle indicates that argininosuccinate synthase (ASS) catalyzes L-citrulline (L-cit) conversion to form argininosuccinate (AS), and subsequent AS cleavage by argininosuccinate lyase (ASL) forms L-arginine (L-arg), the substrate for NO synthesis...
September 7, 2016: Vascular Pharmacology
Hugo F Miranda, Fernando Sierralta, Nicolás Aranda, Viviana Noriega, Juan Carlos Prieto
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may act through others mechanisms, in addition to inhibition of prostaglandin synthesis. These includes cholinergic, NO, serotonergic and opioids pathways. METHODS: The aim of this work was to evaluate the effect of systemic action of (S)-+-ketoprofen (dexketoprofen, DEX) on pain behaviors using the orofacial formalin test in mice and the potential involvement of cholinergic, NO, serotonergic and opioids pathways...
June 25, 2016: Pharmacological Reports: PR
M Alipour, B Amini, F Adineh, H Feizi, M R Jafari
Memory impairment is a common disorder in diabetes mellitus which is associated with hippocampal neuronal apoptosis. The present study was conducted to examine the effect of one-week intraperitoneal (ip), administration of aminoguanidine (AG) on passive avoidance learning (PAL) and Bcl-2 family gene expression in the hippocampus of rats. Sixty male rats were divided into ten groups: non-diabetic/diabetic animals with/without AG (50, 100, 200 and 400 mg/kg, ip) treatment for one week. PAL and Bcl-2 family genes were examined...
2016: Bratislavské Lekárske Listy
Ran Guo, Yan Zheng, Jun-An Ma
A facile and efficient electrophilic reaction of 2,2,2-trifluorodiazoethane (CF3CHN2) with the in situ generated N-heterocyclic carbenes is reported. Under basic conditions, a series of trifluoromethylated N-aminoguanidines were obtained in good to high yields. Furthermore, this protocol was applied in the synthesis of the agrochemical Imidacloprid analogue.
September 2, 2016: Organic Letters
Tomoyuki Moriyama, Masayuki Kemi, Toshiharu Horie
3-Deoxyglucosone (3-DG) is a highly reactive carbonyl intermediate in glycation reaction (also known as Maillard reaction) and plays an important role in diabetic complications. We investigated the potential involvement of 3-DG in doxorubicin (DXR)-induced cardiotoxicity. Male Crl:CD(SD) rats received intravenous injections of DXR at 2mg/kg, once weekly, for 6 weeks, with/without daily intraperitoneal treatment with 3-DG scavenging agents, i.e., aminoguanidine (AG, 25mg/kg/day) and pyridoxamine (PM, 60mg/kg/day)...
September 2016: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Seung Hwan Hwang, Zhiqiang Wang, Soon Sung Lim
This study successfully established the feasibility of a two-step chemo-enzymatic synthesis of l-ascorbyl phenolates. Intermediate vinyl phenolates were first chemically produced and then underwent trans-esterification with l-ascorbic acid in the presence of Novozyme 435® (Candida Antarctica lipase B) as a catalyst. Twenty vinyl phenolates and 11 ascorbyl phenolates were subjected to in vitro bioassays to investigate their inhibitory activity against advanced glycation end products (AGEs). Among them, vinyl 4-hydroxycinnamate (17VP), vinyl 4-hydroxy-3-methoxycinnamate (18VP), vinyl 4-hydroxy-3,5-dimethoxycinnamate (20VP), ascorbyl 4-hydroxy-3-methoxycinnamate (18AP) and ascorbyl 3,4-dimethoxycinnamate (19AP) showed 2-10 times stronger inhibitory activities than positive control (aminoguanidine and its precursors)...
January 1, 2017: Food Chemistry
Nina Javadian, Nastaran Rahimi, Mehrak Javadi-Paydar, Amir Hossein Doustimotlagh, Ahmad Reza Dehpour
Vasopressin neuropeptides play an important role in the several cognitive, social, and neuroendocrine functions. Also, several studies report the involvement of nitrergic system in the vasopressin functions in central nervous system. This study investigates the effect of Arginine-Vasopressin (AVP) in pentylenetetrazol (PTZ)-induced seizures threshold and the probable role of nitric oxide (NO). AVP is administered intraperitoneally (0.01-20μg/kg, i.p.) 30min before induction of seizures. Administration of AVP (0...
October 2016: Epilepsy Research
Danielle J Borg, Josephine M Forbes
Advanced glycation end products (AGEs) are the final products of the Maillard reaction, a complex process that has been studied by food chemists for a century. Over the past 30 years, the biological significance of advanced glycation has also been discovered. There is mounting evidence that advanced glycation plays a homeostatic role within the body and that food-related Maillard products, intermediates such as reactive α-dicarbonyl compounds and AGEs, may influence this process. It remains to be understood, at what point AGEs and their intermediates become pathogenic and contribute to the pathogenesis of chronic diseases that inflict current society...
August 2016: Glycoconjugate Journal
Chamira Dilanka Fernando, Diyathi Tharindhi Karunaratne, Sachith Dilshan Gunasinghe, M C Dilusha Cooray, Prabuddhi Kanchana, Chandani Udawatte, Pathirage Kamal Perera
BACKGROUND: Advanced glycation end products (AGEs) and free radicals are inflammatory mediators and are implicated in many diseases such as diabetes, cancer, rheumatoid arthritis etc. Multi targeted poly herbal drug systems like Nawarathne Kalka (NK) are able to quench the overall effect of these mediators as they contain good combinations of phytochemicals that have least side effects in contrast to modern medicinal drugs. The objectives of this study were to evaluate phytochemical composition, free radical scavenging activity, cytotoxicity and the inhibitory action on the formation of AGEs by aqueous extract of NK...
2016: BMC Complementary and Alternative Medicine
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