Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2 -terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 M, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 M, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction). Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)] 2+ (2) (DIP = 4,7-diphenyl-1,10-phenanthroline; bdt = 1,2-benzenedithiolate; dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine); ptpy = 4'-phenyl-2,2':6',2''-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and photo-index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm 2 ; PI: >4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm 2 ; PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma-mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) S. aureus and Gram-(−) E. coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm 2 ) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(−) E. coli (>4 log10 CFU reduction). 3Introduction.
Consumption and production of bismuth compounds are increasing, however, a little information on the toxic effect and also the effective method in removal of bismuth compounds are available. The present research aimed to characterize the potential efficiency of two chelators after bismuth administration for 55A days following two dose levels of 20 and 40A mg/kg body weight daily to male rats. However, we found abnormalities after bismuth administration in clinical signs, such as body weight, kidneys and liver damages, a black line on gums and skin reactions. Furthermore, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing bismuth from the body was considered. Along this line, two known chelators deferiprone (1, 2-dimethy1-3-hydroxypyride-4-one, L(1)) and desferrioxamine (DFO) were chosen and tested in the acute rat model. Chelators were given orally (L(1)) or intraperitoneally (DFO) as a single or combined therapy for the period of a week. Doses of L(1) and DFO were 110A mg/kg body weight in experiments. Bismuth and iron concentrations in various tissues were determined by graphite furnace and flame atomic absorption spectrometry, respectively. The combined chelation therapy results show that DFO and L(1) are able to remove bismuth ions from the body, whereas iron concentration returned to the normal level and symptoms are also decreased. DFO was more effective than L1 in reducing bismuth concentration in tissues. The efficiency of DFOA +A L(1) is more than DFO or L(1) in removing bismuth from organs. Our results are indicative that the design procedure might be useful for preliminary in-vivo testing of the efficiency of chelating agents. Results of combined chelators' treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for efficiency of chelating agents in bismuth toxicity.
An investigation was conducted to evaluate the ability of DFO following the administration of thallium salt in male Wistar rats. Thallium was introduced to several groups of weanling male Wistar rats via different means, through drink, food and intraperitoneal injection. A control group was fed on a diet containing a normal level of iron. After a period of 30 days, all the rats administered thallium were severely anemic and showed toxicity symptoms through loss of hair, an increase in thallium and a decrease in iron levels in the blood. Chelation therapy was carried out to remove the toxic element from the body. The ability of desferrioxamine (DFO) in removing thallium was investigated by injection of this chelator for one week to the remaining rats of similar groups. The results showed that the thallium level present in the blood was significantly reduced and, at the same time, the iron concentration returned to the normal level. It was concluded that DFO chelator is able to remove thallium from the body and could be used for the treatment of complications and eradication of symptoms of thallium intoxication.
Investigations were conducted to evaluate the ability of two chelators, desferrioxamine (DFO), and deferiprone (1,2-dimethy1-3-hydroxypyride-4-one, L 1 ), for the excretion of vanadium after a period of administration of vanadium salts in 6-week-old male Wistar rats. Immediately after 60 days of vanadium administration, the rats received chelators (L 1 , DFO or L 1 ? DFO) for a period of 1 week. Chelators were given orally (L 1 ), intraperitoneally (DFO), or both to different groups of rats at two different dosage levels. After chelation therapy, animals were sacrificed by exsanguination from abdominal aorta. Blood, kidney, liver, and heart samples were collected and prepared for determination of vanadium and iron concentrations by graphite furnace and flame atomic absorption spectroscopy (GF AAS, and F AAS) methods, respectively. These chelators significantly enhanced the urinary and biliary excretion of vanadium and restored the altered levels of iron. Furthermore, the hypothesis that these two known chelators might be more effective in removing vanadium from the body as a combined treatment than as monotherapy also was tested in this study. Although there is no significant difference between these two chelators in reducing the vanadium concentration, combination therapy (L 1 ? DFO) may cause higher efficacy and lower toxicity compared with monotherapies. Collectively, the results indicate that the designed procedure might be useful for preliminary in vivo testing of the efficiency of a chelating agent. However, our findings regarding the efficacy of combination therapy should be confirmed in more experiments. This preliminary study does not provide all answers to the magnitude of the efficiency of chelating agents in vanadium toxicity, and thus, further research is warranted.
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