Gold(III) compounds are emerging as a new class of metal complexes with outstanding cytotoxic properties and are presently being evaluated as potential antitumor agents. We report here on the solution and electrochemical properties, and the biological behavior of some gold(III) dithiocarbamate derivatives which have been recently proved to be one to 4 orders of magnitude more cytotoxic in vitro than the reference drug (cisplatin) and to be able to overcome to a large extent both intrinsic and acquired resistance to cisplatin itself. Their solution properties have been monitored in order to study their stability under physiological conditions; remarkably, they have shown to undergo complete hydrolysis within 1 h, the metal center remaining in the +3 oxidation state. Their DNA binding properties and ability in hemolyzing red blood cells have been also evaluated. These gold(III) complexes show high reactivity toward some biologically important isolated macromolecules, resulting in a dramatic inhibition of both DNA and RNA synthesis and inducing DNA lesions with a faster kinetics than cisplatin. Nevertheless, they also induce a strong and fast hemolytic effect (compared to cisplatin), suggesting that intracellular DNA might not represent their primary or exclusive biological target.
Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth-inhibitory effects, generally achieved by exploiting non-cisplatin-like mechanisms of action. The rationale of our research work is to combine the antitumor properties of the gold(III) metal center with the potential chemoprotective function of coordinated dithiocarbamates in order to reduce toxic side effects (in particular nephrotoxicity) induced by clinically established platinum-based drugs. In this context, [Au III Br 2 (ESDT)] (AUL12) was proved to exert promising and outstanding antitumor activity in vitro and to overcome both acquired and intrinsic resistance showed by some types of tumors toward cisplatin. As a subsequent extension of our previous work, we here report on detailed in vivo studies in rodents, including antitumor activity toward three transplantable murine tumor models, toxicity, nephrotoxicity and histopathological investigations. Remarkably, the gold(III) complex AUL12 stands out for higher anticancer activity than cisplatin toward all the murine tumor models examined, inducing up to 80% inhibition of tumor growth. In addition, it shows low acute toxicity levels (lethal dose, LD 50 5 30 mg kg 21 ) and reduced nephrotoxicity. Altogether, these results confirm the reliability of our drug design strategy and support the validation of this gold(III)-dithiocarbamato derivative as a suitable candidate for clinical trials.The accidental discovery of the anticancer properties of cisplatin (cis-dichlorodiammineplatinum(II), cis-[Pt II Cl 2 (NH 3 ) 2 ]; Fig. 1) in the mid-1960s 1 has triggered the development of both platinum 2 -and other metal-based 3,4 alternative compounds. Although well-established in current cancer chemotherapy, the use of platinum compounds for the treatment of tumor diseases is massively hampered by severe side effects such as nausea, alopecia, ototoxicity, neurotoxicity, myelosuppression, nephrotoxicity and tumor resistance, either intrinsic or acquired during cycles of therapy. 5 Consequently, the development of novel metallodrugs showing a different pharmacological profile is a major goal of modern medicinal chemistry and drug design.Among the non-platinum antitumor agents, gold complexes have recently gained increasing attention because of their strong inhibitory effects on tumor cell growth, generally achieved by exploiting non-cisplatin-like pharmacodynamic and pharmacokinetic properties and mechanisms of action. 6,7 Owing to their traditional use in medicine for the treatment of rheumatoid arthritis, gold derivatives are suitable candidates as potential alternatives to platinum drugs. In fact, the antiarthritic activity arises from their known immunosuppressive and anti-inflammatory actions, thus establishing, at least in principle, a connection between the two therapies. Moreover, gold(III) complexes show chemical features that are very close to those of clinically established platinum(II) derivatives, such as the pre...
Multivariate analysis indicated that age was the primary predictor, and noise and ultrasound exposure the secondary predictors of hearing thresholds in the high-frequency range. The results suggest that HFA could be useful in the early diagnosis of noise-induced hearing loss in younger groups of workers (under 30 years of age).
UV radiation is known to cause acute and chronic eye and skin damage. The present case report describes a 90 min accidental exposure to UV-C radiation of 26 medical school students. Germicidal lamps were lit due to a malfunctioning of the timer system. Several hours after irradiation exposure, all subjects reported the onset of ocular symptoms, subsequently diagnosed as photokeratitis, and skin damage to the face, scalp and neck. While the ocular symptoms lasted 2-4 days, the sunburn-like condition produced significant erythema followed by deep skin exfoliation. The irradiation was calculated to be approximately 700 mJ cm(-2) absorbed energy, whereas the actual radiation emitted by the lamps was 0.14 mW cm(-2) (the radiometric measurements confirmed these calculi, because the effective irradiance measured from the height of the autopsy table to about 1 m under the UV-C lamp varied from 0.05 to 0.25 mW cm(-2)) but, more likely, the effective irradiance, according to skin phototype and symptoms, was between 50 and 100 mJ cm(-2). The ocular and skin effects produced by such a high irradiation (largely higher than that accepted by the American Conference of Governmental Industrial Hygienists [ACGIH] threshold limit values [TLVs]) appeared reversible in a relatively short time.
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