The Influence of Very Low Doses of Cisplatin on Tumor Cell Proliferation In Vitro and on Some Hematological and Enzymatic Parameters of Healthy Rats

Healthy rats had been treated for 2 or 6 weeks with 1.0 mL of 10−8 and 10−16 mg/mL of cisplatin. After 2 weeks of treatment, a significant increase in leukocyte and erythrocyte count and also in hematocrit was observed. Among leukocytes the number of neutrophils and eosinophils significantly increased. Biochemical analyses indicated a decrease in the glycogen content in the liver and kidneys after 2 weeks of treatment with low doses of cisplatin but at the end of the experiment (8th week of experiment) the stores of glycogen increased significantly. Biochemical analyses concerning the activity of some enzymes in the liver revealed a significant increase of peroxidase and acid phosphatase as well as catalase activities after 2 weeks of treatment. However, catalase was induced by a very low concentration of cisplatin, 10−16 mg/mL. After the cessation of cisplatin treatment the activity of enzymes returned to normal values

Biologically and chemically important hydrazino-containing imidazolines as antioxidant agents

<p>Biologically and chemically useful hydrazinoimidazolines were evaluated as antioxidant and antihaemolytic agents. 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH^•), galvinoxyl radical (GOR), nitric oxide (NO) and hydrogen peroxide (H₂O₂) scavenging assays, ferric ions reducing power assay, and <i>ex vivo</i> model of rat erythrocytes exposed to 2,2′-azobis(2-methylpropionamidine)dihydrochloride (AAPH) or H₂O₂ were used. The most potent DPPH^• scavengers proved to be hydrazinoimidazolines <b>3</b>, <b>2</b>, and <b>4</b>, revealing excellent antiradical effects – superior or comparable to that of all antioxidant standards used. Moreover, these molecules showed strong NO neutralising potencies – better to that of ascorbic acid (AA) (<b>3</b>), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) (<b>3</b> and <b>2)</b>, butylated hydroxytoluene (BHT) (<b>3</b> and <b>2</b>), and butylated hydroxyanisole (BHA) (<b>3</b>, <b>2</b>, and <b>4</b>). Compound <b>4</b> was also effective in GOR scavenging. The excellent scavenger of GOR, NO, and H₂O₂ proved to be structure <b>5</b>, with the potency superior or comparable to the majority of antioxidant standards used. In turn, compound <b>9</b> was effective in H₂O₂ and GOR neutralisation. All hydrazinoimidazolines revealed the reducing power that is higher than BHT. Moreover, the protective effects of most test compounds on oxidatively stressed erythrocytes were observed. Some structure–activity relationships were disclosed. A significance of the primary hydrazino group on antioxidant effects was confirmed. The most likely DPPH^• and GOR scavenging mechanisms for test compounds were propound. Among all the investigated molecules, hydrazinoimidazolines <b>5</b>, <b>3</b>, <b>2</b>, <b>4</b>, and <b>9</b>, due to their excellent or good antiradical activities, can represent promising antioxidant candidates with prospective utility for prevention of diseases related to reactive oxygen/nitrogen species.</p

Hyperreactivity of Blood Leukocytes in Patients with NAFLD to Ex Vivo Lipopolysaccharide Treatment Is Modulated by Metformin and Phosphatidylcholine but Not by Alpha Ketoglutarate.

Toll-like receptor 4 and proinflammatory cytokines play a central role in the progression of nonalcoholic fatty liver disease. We investigated IL-1, IL-6 and TNFα production and toll-like receptor 4 in both--obese and lean patients with non-alcoholic fatty liver disease who met different sets of metabolic syndrome criteria and linked the results with the disease burden.95 subjects were divided into four groups depending on the following criteria: presence or absence of metabolic syndrome and/or non-alcoholic fatty liver disease, glucose tolerance (prediabetes or normoglycemia) and BMI value (obese or lean). We determined the levels of IL-1β, IL-6, TNFα, and monocyte toll-like receptor 4 expression in fresh blood as well as in blood cultures treated with lipopolysaccharide with or without metformin, alphaketoglutarate or phosphatidylcholine supplementation.The blood leukocytes of patients with non-alcoholic fatty liver disease are hypersensitive to lipopolysaccharide treatment and produce elevated levels of pro-inflammatory cytokines in response to ex vivo treatment with lipopolysaccharide. Moreover, they overexpress toll-like receptor-4. Hyperreactivity was typical mainly for obese patients with non-alcoholic fatty liver disease together with metabolic syndrome and decreased with the severity of disease. Metformin was the most effective in attenuation of hyperreactivity in all groups of patients with non-alcoholic fatty liver disease, but in obese patients the effectiveness of metformin was weaker than in lean. The reduction of cytokine level by metformin was accompanied by the decrease in toll-like receptor-4 expression. phosphatidylcholine also attenuated hyperreactivity to lipopolysaccharide but mainly in obese patients. Alpha ketoglutarate did not modulate cytokines' level and toll-like receptor 4 expression in non-alcoholic fatty liver disease patients.Metformin and phosphatidylcholine attenuated lipopolysaccharide induced toll-like receptor 4 overexpression and overproduction of pro-inflammatory cytokines; however, their efficacy depended on combined presence of non-alcoholic fatty liver disease, metabolic syndrome and obesity

Chemerin, retinol binding protein-4, cytokeratin-18 and transgelin-2 presence in sera of patients with non-alcoholic liver fatty disease

Background. Chemerin and retinol binding protein-4 (RBP-4) are adipokines which may play a role in the progression of NAFLD. It has been also suggested that cytokeratin-18 (CK-18) could be a marker of hepatocyte caspase-directed death while transgelin-2 production could reflect stage of liver fibrosis. The aim of this study was to evaluate the level of the above adipokines in sera of patients with NAFLD and determine the relation between the level of transgelin-2 and fibrosis-4 index (FIB-4).Material and methods. Ninety-five subjects included initially to the study were divided into four groups: (I) prediabetics, obese with NAFLD and metabolic syndrome (Ms), (II) lean with NAFLD and without MS, (III) obese without NAFLD and MS, and (IV) healthy individuals. We determined the levels of chemerin, RBP-4, transgelin-2 and CK-18 fragments in sera of patients with NAFLD. Moreover, we examined if the levels of CK-18 fragments and transgelin-2 correlates with FIB4 value. Results. Chemerin and RBP-4 were highly expressed in sera of all NAFLD, especially in obese individuals. Chemerin level was also linked to MS. High level of serum CK-18 fragments and transgelin-2 did not correlate with obesity and MS, but seemed to correlate with progression of NAFLD to liver fibrosis.Conclusions. In conclusion, the production of the two adipokines, chemerin and RBP-4, is strongly associated with obesity in patients with NAFLD. Serum concentrations of CK-18 fragments and transgelin-2 correlate with the severity of NAFLD, but not with obesity