Cancer cell mitochondria represent an attractive target for oncological treatment as they have unique hallmarks that differ from their healthy counterparts, as the presence of a stronger membrane potential that can be exploited to specifically accumulate cytotoxic cationic molecules. Here, we explore the selective cytotoxic effect of 10-N-nonyl acridine orange (NAO) on human lung carcinoma H520 cells and compare them with healthy human lung primary fibroblasts. NAO is a lipophilic and positively charged molecule that promotes mitochondrial membrane adhesion that eventually leads to apoptosis when incubated at high micromolar concentration. We found an enhanced cytotoxicity of NAO in H520 cancer cells. By means Fluorescence lifetime imaging microscopy (FLIM) we also confirmed the formation of H-dimeric aggregates originating from opposing adjacent membranes that interfere with the mitochondrial membrane structure. Based on our results, we suggest the mitochondrial membrane as a potential target in cancer therapy to mechanically control the cell proliferation of cancer cells.
ANTIMICROBIAL agents are usually combined with NSAIDs to treat various systemic infections accompanied by fever and other inflammatory conditions. They can also be administered with steroidal anti-inflammatory drugs (SAIDs) to relieve suffering caused by inflammation. A pharmacological interaction between the two types of drug has been described in previous studies (Post and others 2002, 2003, Sidhu and others 2010, Ogino and others 2005). The combined use of anti-inflammatory and antimicrobial drugs is common clinical practice in young buffaloes due to enteric and respiratory infections, which are a significant problem and usually result in economic losses in nursing calves (Bukhari and others 2010). This short communication aimed to establish, in this species, the serum concentration-time profile and pharmacokinetic parameters of marbofloxacin (MBF), after intramuscular administration alone and in combination with intramuscular administration of ketoprofen (KPF), flunixin meglumine (FM) or dexamethasone (DXM), and to integrate pharmacokinetic/pharmacodynamic (PK/PD) data. Twenty-four, seven-to 15-day-old clinically healthy buffalo calves (mean [sd] weight 60.43 [6.75] kg) were included in the study and randomly allocated to one of four treatment groups. A parallel design was used, taking into account the age of the selected animals. All groups received a 2 mg/kg dose of MBF intramuscularly in the semitendinous muscle. The first group received only MBF, while the other three groups also received a dose of one of three drugs: 3 mg/kg KPF (MBF+KTF), 2.5 mg/kg FM (MBF+FM) or 0.1 mg/kg DXM (MBF+DXM) intramuscularly in the opposite semitendinous muscle. The study was approved by the Animal Experimentation Ethics
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