Influence of sevoflurane anesthesia with mechanical ventilation and fluid-therapy on distribution of subcutaneously administered robenacoxib in dogs.

Robenacoxib is a novel nonsteroidal anti-inflammatory drug approved for dogs. The present study aimed to evaluate influences of sevoflurane anesthesia on the distribution of robenacoxib in dogs. Ten healthy beagle dogs (1 to 11 years old, 9.3 to 14.3 kg body weight, 6 males and 4 females) were subcutaneously administered robenacoxib (2 mg/kg) under conscious condition or sevoflurane anesthesia inhaled a 1.3-fold predetermined individual minimum alveolar concentration of sevoflurane at a 28-day interval. The dogs under sevoflurane anesthesia were also mechanically ventilated and received fluid-therapy. On each occasion, serum samples were collected from the dogs before and at 5, 15, 30, 60, 120, 180, and 240 min after the robenacoxib administration. Serum robenacoxib concentration was measured by a liquid chromatography-tandem mass spectrometry. Maximum serum concentration of robenacoxib (Cmax) was 2.2 µg/ml [range: 1.2-4.6] (median [range: minimum-maximum]) and time of Cmax (Tmax) was 90 min [range: 60-120] in the conscious dogs. In the sevoflurane-anesthetized dogs, the Cmax significantly declined (1.3 µg/ml [range: 0.8-1.4], P=0.008) and Tmax was delayed (120 min [range: 120-240], P=0.018) compared with those in the conscious dogs. The serum robenacoxib concentration at 240 min (C240) decreased to 0.5 µg/ml [range: 0.2-0.9] in the conscious dogs, while it remained higher in the sevoflurane-anesthetized dogs (1.0 µg/ml [range: 0.3-1.4], P=0.011). In conclusion, the anesthetic procedure with sevoflurane, mechanically ventilated, and received fluid-therapy might affect the pharmacokinetics of subcutaneously administered robenacoxib in dogs.

C-terminal domain of human CAP18 antimicrobial peptide induces apoptosis in oral squamous cell carcinoma SAS-H1 cells.

Mammalian myeloid and epithelial cells express many antimicrobiotic peptides that contribute to innate host defense against invading microbes. In the present study, a 27-mer peptide of the C-terminal domain (hCAP18(109-135)) and analogs of the antimicrobial peptide human cathelicidin LL-37/human cationic antimicrobial protein 18 (hCAP18) were examined for tumoricidal activity. In vitro results showed that hCAP18(109-135) induced apoptosis in human oral squamous cell carcinoma (OSCC), SAS-H1 cells. The hCAP18(109-135) induced mitochondrial depolarization and apoptosis in SAS-H1 cells, but not in healthy human gingival fibroblasts (HGF) and human keratinocyte line HaCaT cells. Caspases were not activated during hCAP18(109-135)-induced apoptosis in SAS-H1 cells. The results indicate that hCAP18(109-135) may induce caspase-independent apoptosis in OSCC but not in normal cells. hCAP18(109-135) can therefore be a useful anti-tumor therapeutic agent in the treatment of OSCC.