Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin

Objective: The present study was designed to investigate the chemoprotective efficacy of an L-cysteine-based oxovanadium (IV) complex, namely, oxovanadium (IV)-L-cysteine methyl ester complex (VC-IV) against cisplatin (CDDP)-induced renal injury in Swiss albino mice.

Methods: CDDP was administered intraperitoneally (5 mg/kg body weight) and VC-IV was administered orally (1 mg/kg body weight) in concomitant and 7 days pre-treatment schedule.

Results: CDDP-treated mice showed marked kidney damage and renal failure. Administration of VC-IV caused significant attenuation of renal oxidative stress and elevation of antioxidant status. VC-IV also significantly decreased serum levels of creatinine and blood urea nitrogen, and improved histopathological lesions. Western blot analysis of the kidneys showed that VC-IV treatment resulted in nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) through modulation of cytosolic Kelch-like ECH-associated protein 1. Thus, VC-IV stimulated Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and enhanced activity of antioxidant enzymes. Interestingly, VC-IV did not alter the bioavailability and renal accumulation of CDDP in mice.

Discussion: In this study, VC-IV exhibited strong nephroprotective efficacy by restoring antioxidant defense mechanisms and hence may serve as a promising chemoprotectant in cancer chemotherapy.     

Adjustment of flight speed of gregarious desert locusts (Orthoptera: Acrididae) flying side by side

In tethered flying locusts, optomotor thrust responses induced by translatory pattern motion within the lateral visual fields were studied under closed-loop conditions. By modulating thrust in a compensatory manner, locusts counteracted a bias motion superposed on the thrust-related motion. This way, pattern speed was kept at 0° s^–1, indicating the set point of the respective optomotor control circuit. Though the quality of bias compensation varied greatly, it was largely independent from pattern characteristics. It might indicate that the gain of behavior not only is controlled by an automatic mechanism but also is affected by spontaneous modulations. Compensation of bias motion was critically dependent on the relation between self- and bias-generated motion: Locusts did not take control over pattern motion if self- and bias-generated motion differed greatly. Instead, locusts adopted a constant, supposingly preferred, thrust value. Therefore, flight speed is assumed to be controlled by two systems: the optomotor and a preferred thrust system. In free flight, an equalization of the flight speed of locusts within a swarm might result from similar behavior. In combination with a presumed coordination of the locusts' course direction, this may explain the continued cohesion of swarms in the field.     

Pharmacologic markers predictive of neutropenia chemically induced by cisplatin (CDDP)

The aim of this study was to demonstrate the value of the level of platinum in lymphocytes, plasma and saliva, in order to predict neutropenia during the same cycle after cisplatin chemotherapy. Plasma and lymphocytes samples were obtained from 14 patients receiving 100 mg/m2 cisplatin in different combination. Saliva samples were obtained from 3 other patients. We found that platinum plasma concentration at the Cmax and 1 hour after the end of the infusion were significantly higher in the grade 4 neutropenia cycles (respectively 2.60 vs 2.05 and 2.55 vs 2.00 mg/l p < 0.05). Platinum DNA-adduct were not detectable by ICPMS. Maximum concentrations in saliva ranged between 0.05 to 0.08 mg/l at the end of the infusion. The ratio of platinum levels in plasma and saliva varied between 2 and 3%. Saliva seems to be useful for therapeutic drug monitoring of cisplatin because it can be obtained by non invasive and patient-friendly-means. However, new studies are required to demonstrate the relationship between these two biological fluids.     

Sodium butyrate enhances the cytotoxic effect of cisplatin by abrogating the cisplatin imposed cell cycle arrest

Background  

Histone deacetylase inhibitors have been proposed as potential enhancers of the cytotoxic effect of cisplatin and other anticancer drugs. Their application would permit the use of lower therapeutic doses and reduction of the adverse side effects of the drugs. However, the molecular mechanisms by which they sensitize the cells towards anticancer drugs are not known in details, which is an obstacle in developing effective therapeutic protocols.     

Time-resolved polarization imaging by pump-probe (stimulated emission) fluorescence microscopy

We report the application of pump-probe fluorescence microscopy in time-resolved polarization imaging. We derived the equations governing the pump-probe stimulated emission process and characterized the pump and probe laser power levels for signal saturation. Our emphasis is to use this novel methodology to image polarization properties of fluorophores across entire cells. As a feasibility study, we imaged a 15-microm orange latex sphere and found that there is depolarization that is possibly due to energy transfer among fluorescent molecules inside the sphere. We also imaged a mouse fibroblast labeled with CellTracker Orange CMTMR (5-(and-6)-(((4-chloromethyl)benzoyl)amino)tetramethyl-rhodamine). We observed that Orange CMTMR complexed with gluthathione rotates fast, indicating the relatively low fluid-phase viscosity of the cytoplasmic microenvironment as seen by Orange CMTMR. The measured rotational correlation time ranged from approximately 30 to approximately 150 ps. This work demonstrates the effectiveness of stimulated emission measurements in acquiring high-resolution, time-resolved polarization information across the entire cell.     

Detection of sulfur-containing compounds in control and cadmium-exposed rat organs by high-performance liquid chromatography--vacuum-ultraviolet inductively coupled plasma-atomic emission spectrometry (HPLC-ICP)

Sulfur-containing compounds in biological samples were separated by high-performance gel permeation chromatography and detected with a vacuum-ultraviolet inductively coupled plasma-atomic emission spectrometer. Distribution profiles of sulfur in the supernatants of liver, kidney, spleen, lung, and pancreas of control and cadmium-exposed rats were determined along with cadmium, copper, iron, phosphorus, and zinc profiles. Changes in sulfur distribution were induced by cadmium exposure not only in the metallothionein fraction, but also in the high-molecular-weight protein fraction, indicating the effect of cadmium exposure on diverse endogenous sulfur-containing compounds. Glutathione and taurine also were detected simultaneously as distinct peaks.     

Novel emission properties of melem caused by the heavy metal effect of lanthanides(III) in a LB film.

A novel emissive molecular system is constructed by the intercalation of the fluorophore melem (triamino-tri-s-triazine) within a Langmuir-Blodgett (LB) film of stearic acid with the periodic arrangement of lanthanides (Ln(III)), mainly Pr(III) with supporting of Eu(III). From emission spectra, decay curves, quantum yields and XPS measurements, it is clarified that the external heavy metal effect of Pr(III) on melem is much stronger in the film than in the bulk solid state, resulting in producing an unusual triplet state of melem. The triplet state of melem in the LB film donates the excitation energy to Pr(III) in the LB film, which is completely different from the energy transfer pathway of Pr-melem complex in the solid state through the singlet state of melem.     

Flanking bases influence the nature of DNA distortion by platinum 1,2-intrastrand (GG) cross-links

The differences in efficacy and molecular mechanisms of platinum anti-cancer drugs cisplatin (CP) and oxaliplatin (OX) are thought to be partially due to the differences in the DNA conformations of the CP and OX adducts that form on adjacent guanines on DNA, which in turn influence the binding of damage-recognition proteins that control downstream effects of the adducts. Here we report a comprehensive comparison of the structural distortion of DNA caused by CP and OX adducts in the TGGT sequence context using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations. When compared to our previous studies in other sequence contexts, these structural studies help us understand the effect of the sequence context on the conformation of Pt-GG DNA adducts. We find that both the sequence context and the type of Pt-GG DNA adduct (CP vs. OX) play an important role in the conformation and the conformational dynamics of Pt-DNA adducts, possibly explaining their influence on the ability of many damage-recognition proteins to bind to Pt-DNA adducts.     

Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats

The effect of aminoguanidine (AG) on nephrotoxicity induced by cisplatin (CDDP) was investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced nephrotoxicity, manifested biochemically by a significant elevation in serum urea, creatinine and a severe decrease in serum albumin. Moreover, marked increases in kidney weight, urine volume and urinary excretion of albumin were observed. Nephrotoxicity was further confirmed by a significant decrease in glutathione-S-transferase (GST, E.C. 2.5.1.18), glutathione peroxidase (GSH-Px, E.C. 1.11.1.9) and catalase (E.C. 1.11.1.6) and a significant increase in lipid peroxides measured as malondialdhyde (MDA) in kidney homogenates. Administration of AG (100 mg/kg per day p.o.) in drinking water 5 days before and 5 days after CDDP injection produced a significant protection against nephrotoxicity induced by CDDP. The amelioration of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations. In addition, AG tended to normalize decreased levels of serum albumin. Urine volume, urinary excretions of albumin and GST and kidney weight were significantly decreased. Moreover, AG prevented the rise of MDA and the reduction of GST and GSH-Px activities in the kidney. These results suggest that AG has a protective effect on nephrotoxicity induced by CDDP and it may therefore improve the therapeutic index of CDDP.     

Nested-PCR检测恒河猴泡沫病毒

目的用nested-PCR检测恒河猴泡沫病毒SFV的前病毒形式。方法从SFV-1的pol区域选择两对引物分别对原代猴肾细胞（rhesus monkey kidney,RMK）及猴外周血淋巴细胞（peripheral blood lymphocytes,PBLs）进行体外扩增,扩增产物经1.0%的琼脂糖凝胶电泳,证实其特异性。阳性对照使用具有典型泡沫样病变的RMK377细胞株的前病毒DNA,阳性对照的PCR扩增产物经测序证实,阴性对照为恒河猴的SRV-1cDNA。结果nested-PCR能快速灵敏的直接从猴外周血淋巴细胞检出SFV的前病毒形式,与RMK细胞培养结果基本相一致。结论本实验所建立的检测SFV的nested-PCR法能快速准确的检测猴群中的SFV的带毒情况,对于提高实验猴的质量具有重要意义。     

Growth, light interception and disease in field bean (Vicia faba): the effect of late infection by Ascochyta fabae

Growth and light interception were measured in field beans (Vicia faba) infected by Ascochyta fabae under field conditions. Despite late infection, disease reduced the leaf area index and the dry matter production of the crop. The main effect was due to a decrease of leaf area duration, which resulted in shorter duration of growth and lower final dry weights. The reduction in seed yield was significant, representing a decrease of 15% compared with a prophylactic fungicide treatment. The data are consistent with a small reduction in light use efficiency, but the observed differences were not significant during the period of crop growth.     

Segregation distortion of isozyme loci in cherimoya (Annona cherimola Mill)

The allelic segregation of 13 isozyme loci in hand-fertilized heterozygous cherimoya trees (Annona cherimola Mill.) has been studied. We analyzed 63 locus x progeny combinations and found non-Mendelian segregation in 12 cases. The sequential Bonferroni method revealed only eight cases of non-Mendelian segregation; these have been investigated with several chi-square tests to discover what processes were involved. Gametic selection appears to be the main contributor, although zygotic selection seems also to play a part.     

Inhibitory effect of cisplatin and [Pt(dach)Cl2] on the activity of phospholipase A2

This work has been focused on testing the influence of two selected Pt(II) complexes cisplatin, Pt(NH₃)₂Cl₂, and [Pt(dach)Cl₂] on the activity of porcine pancreatic phospholipase A₂ (PLA₂). It has been assumed that this enzyme plays a role in carcinogenesis and that it could be a target in the tumour therapy. The results of this study show that both Pt(II) complexes inhibit the activity of the enzyme, though they bind to it in a different manner. While cisplatin interacts with the enzyme in an acompetitive manner, the stable interaction of [Pt(dach)Cl₂] with PLA₂ could not be detected under our experimental conditions.