Toxic effects of fatty acid anilides on the oxygen defense systems of guinea pig lungs and erythrocytes

Toxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even though the etiology and pathogenesis of this disease are not fully known, it is quite clear that generation of free radicals caused by ingestion of fatty acid anilides is responsible for the pathogenetic mechanism in many TOS patients. Fatty acid anilides may also alter the free radical status of lungs and erythrocytes; this possibility may shed some light on understanding toxic oil syndrome. The present study describes the effects of oral administration of fatty acid anilides on the activities of major enzymes involved in the oxygen defense systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a decrease in the SOD activity in lungs. GSH-Px activity was not significantly changed in erythrocytes but was decreased in lungs. Although the activity of catalase was increased only by a higher dose in the erythrocytes, it was not affected in the lung at any dosage. Even though the ingestion of fatty acid anilides caused an increase in the SOD activity in the erythrocytes and a decrease in the SOD activity in the lungs, there was an increase in the lipid peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is probably caused by the accumulation of H₂O₂, and that in the lungs is due to the accumulation of superoxide anion.     

Heat-stress induced inhibition in growth and chlorosis in mungbean (<Emphasis Type="Italic">Phaseolus aureus</Emphasis> Roxb.) is partly mitigated by ascorbic acid application and is related to reduction in oxidative stress

The rising temperatures (>35°C) are proving detrimental to summer-sown mungbean genotypes that experience inhibition of vegetative and reproductive growth. In the present study, the mungbean plants growing hydroponically at varying temperatures of 30/20°C (control), 35/25, 40/30, and 45/35°C (as day/night 12 h/12 h) with (50 μM) or without ascorbic acid (ASC) were investigated for effects on growth, membrane damage, chlorophyll loss, leaf water status, components of oxidative stress, and antioxidants. The ASC-treated plants showed significant improvement in germination and seedling growth especially at 40/30 and 45/35°C. The damage to membranes, loss of water, decrease in cellular respiration, and chlorophyll were significantly prevented by ASC treatment to plants growing at these temperatures. The oxidative stress measured as malondialdehyde and hydrogen peroxide content was observed to be significantly lower at high temperatures with ASC application. The activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase increased at 40/30°C but decreased at 45/35°C in the absence of ASC while with its application, the activities of these enzymes were appreciably resorted. Among all the antioxidants, the endogenous ASC content decreased to the greatest extent at 45/35°C grown plants indicating its vital role in affecting the response of mungbean to heat stress. Exogenously applied ASC raised its endogenous content along with that of glutathione and proline at 45/35°C. The findings indicated that heat stress-induced inhibition in growth and chlorosis was associated with decrease in leaf water status and elevation of oxidative stress, which could partly be prevented by exogenous application of ASC. Its role in imparting protection against heat stress is discussed.     

Sidedness of interfacial arginine residues and anti-atherogenicity of apolipoprotein A-I mimetic peptides

To test the hypothesis that sidedness of interfacial arginine (Arg) in apoA-I mimetic peptides, similar to that observed in apoA-I (Bashtovyy, D. et al. 2011. Sequence conservation of apolipoprotein A-I affords novel insights into HDL structure-function. J. Lipid Res. 52: 435–450.), may be important for biological activity, we compared properties of 4F and analogs, [K^4,15>R]4F and [K^9,13>R]4F, with Lys>Arg substitutions on the right and left side, respectively, of the 4F amphipathic helix. Intraperitoneal administration of these peptides into female apoE null mice (n = 13 in each group) reduced en face lesions significantly compared with controls; 4F and [K^4,15>R]4F were equally effective whereas [K^9,13>R]4F was less effective. Turnover experiments indicated that [K^4,15>R]4F reached the highest, whereas [K^9,13>R]4F had the lowest, plasma peak levels with a similar half life as the [K^4,15>R]4F analog. The half life of 4F was two times longer than the other two peptides. The order in their abilities to associate with HDL in human plasma, generation of apoA-I particles with pre-β mobility from isolated HDL, lipid associating ability, and sensitivity of lipid complexes to trypsin digestion was: 4F>[K^4,15,>R]4F>[K^9,13>R]4F. These studies support our hypothesis that the sidedness of interfacial Arg residues in the polar face of apoA-I mimetics results in differential biological properties.     

Ring-substituted quinolines. Part 2: Synthesis and antimycobacterial activities of ring-substituted quinolinecarbohydrazide and ring-substituted quinolinecarboxamide analogues

Additional structural modifications of the new chemical entity, 2,8-dicyclopentyl-4-methylquinoline (DCMQ; MIC = 6.25 μg/mL, M. tuberculosis H37Rv) resulted in the synthesis of four new series of the ring-substituted quinolinecarbohydrazides (series 1–4) constituting 22 analogues. All new derivatives were evaluated for in vitro antimycobacterial activities against drug-sensitive M. tuberculosis H37Rv strain. Certain ring-substituted-2-quinolinecarbohydrazide analogues described herein showed good inhibitory activity. In particular, analogues 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d), 4,5-dicyclopentyl-2-quinolinecarbohydrazide (2e), 4,8-dicyclopentyl-2-quinolinecarbohydrazide (2f), and 4,5-dicyclohexyl-2-quinolinecarbohydrazide (2g) have exhibited the MIC value of 6.25 μg/mL. Further investigation of the most suitable lead prototype, 4-(1-adamantyl)-2-quinolinecarbohydrazide (2d, series 1) led to the synthesis of N2-alkyl/N2,N2-dialkyl/N2-aryl-4-(1-adamantyl)-2-quinolinecarboxamides (series 5) consisting of 13 analogues. Some of the synthesized carboxamides 7a, 7h, and 7m reported herein have exhibited excellent antimycobacterial activities in the range of 6.25–3.125 μg/mL against drug-sensitive and drug-resistant M. tuberculosis H37Rv strains.     

CD8 alpha+, but not CD8 alpha-, dendritic cells tolerize Th2 responses via contact-dependent and -independent mechanisms, and reverse airway hyperresponsiveness, Th2, and eosinophil responses in a mouse model of asthma

Splenic CD8alpha+ dendritic cells reportedly tolerize T cell responses by inducing Fas ligand-mediated apoptosis, suppressing IL-2 expression, or catabolizing T cell tryptophan reserves through expression of IDO. We report in this study that CD8alpha+, but not CD8alpha-, dendritic cells purified from the spleens of normal mice can tolerize the Th2 responses of cells from asthma phenotype mice through more than one mechanism. This tolerance could largely be reversed in vitro by anti-IL-10 or anti-TGFbeta Ab treatment. However, loss of direct dendritic cell-T cell contact also reduced tolerance, although to a lesser extent, as did adding the IDO inhibitor 1-methyltryptophan or an excess of free tryptophan to the cultures. Within 3 wk of reconstituting asthma phenotype mice with 1 x 10(5) OVA-pulsed CD8alpha+, but not CD8alpha-, dendritic cells, the mice experienced a reversal of airway hyperresponsiveness, eosinophilic airway responses, and pulmonary Th2 cytokine expression. This data indicates that CD8alpha+ dendritic cells can simultaneously use multiple mechanisms for tolerization of T cells and that, in vivo, they are capable of tolerizing a well-established disease complex such as allergic lung disease/asthma.     

Alterations in binding characteristics of peripheral benzodiazepine receptors in testes by vitamin A deficiency in guinea pigs

The correlation of vitamin A with the binding characteristics of peripheral benzodiazepine receptors (PBRs) in testes have been implicated on the basis of findings of involvement of vitamin A in testicular physiology and the abundance of PBRs in testicular tissue. Both vitamin A and PBRs are involved in the control of cell proliferation and differentiation but no data exists regarding the relationship between them. In the present study, we have examined the effects of vitamin A deficiency on the affinity and density of PBRs in testes of guinea pigs. Weanling guinea pigs were divided into three groups: control, pair-fed control and vitamin A deficient. They were fed a complete semipurified diet. The vitamin A deficient diet was similar to the control diet except vitamin A palmitate was omitted. Vitamin A deficiency status was achieved after 90 days of feeding. Binding of [³H]Ro 5-4864, a specific ligand for peripheral benzodiazepine receptors was determined in whole homogenate of testicular tissue. There was a 77% decrease in the receptor density (B_max) in vitamin A deficient group compared to control. The B_maxvalues for control, pair-fed control and vitamin A deficient groups were: 12.4 ± 0.4, 8.8 ± 0.2 and 3.0 ± 0.6 pmol/g, respectively. The equilibrium dissociation constant (K_D) values were also 86% decreased in the vitamin A deficient group compared to the other groups. The K_D values for control, pair-fed control and vitamin A deficient groups were: 3.4 ± 0.7, 2.8 ± 0.5 and 0.5 ± 0.01, respectively. The decrease in the binding characteristics of PBRs in testes due to vitamin A deficiency was accompanied with a corresponding decrease in the levels of testosterone in plasma. These results suggest a close functional relationship of vitamin A with PBRs in testes.     

Inhibition of camel lens zeta-crystallin by aspirin and aspirin-like analgesics.

Camel lens zeta-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibition in a dose-dependent, but time-independent manner. Analysis of inhibition kinetics revealed that aspirin was uncompetitive inhibitor (K(i) 0.64 mM) with respect to NADPH and non-competitive inhibitor (K(i) 1.6 mM) with respect to the substrate, 9,10-phenanthrenequinone (PQ). Multiple-inhibition analysis showed that aspirin and pyridoxal 5' phosphate (PAL-P), a lysine specific reagent, simultaneously bound to a critical lysine residue located towards the NADPH binding region. Consistent with this, NADPH was able to substantially protect zeta-crystallin against aspirin, whereas PQ did not provide any protection. The results suggested that an essential lysine residue was the locus of aspirin binding. The inhibition of zeta-crystallin by aspirin and aspirin-like analgesics was reversible thus eliminating acetylation as a mechanism for inhibition. Reversible binding of aspirin to this lysine may cause steric hindrance resulting in uncompetitive inhibition with respect to NADPH.     

Comparative response of maize and rice genotypes to heat stress: status of oxidative stress and antioxidants

In the present study, two genotypes each of maize and rice were compared for their response to varying degrees of temperature stress (35/30, 40/35, 45/40°C) with controls growing at 30/25°C. At elevated temperatures of 40/35 and 45/40°C, the rice genotypes were inhibited to a significantly higher extent, especially for their shoot growth compared to maize genotypes. The stress injury measured as damage to membranes, loss of chlorophyll and reduction in leaf water status was significantly higher in rice plants, especially at 45/40°C. The components of oxidative stress particularly the level of malondialdehyde was significantly greater in rice plants while the differences for hydrogen peroxide concentrations were small at 40/35 and 45/40°C. The expression of enzymatic antioxidants like catalase, ascorbate peroxidase and glutathione reductase was found to be higher in maize plants compared to rice plants while no variations existed for superoxide dismutase at 45/40°C. In addition, the non-enzymatic antioxidants like ascorbic acid, glutathione and proline were maintained at significantly greater levels at 45/40°C in maize than in rice genotypes. These findings suggested that maize genotypes were able to retain their growth under high-temperature conditions partly due to their superior ability to cope up with oxidative damage by heat stress compared to rice genotypes. Since, maize and rice belong to C₄ and C₃ plant groups, respectively, these observations may also reflect the relative sensitivity of these plant groups to heat stress.