Effects of kanamycin and streptomycin on histamine release from rat mast cells were examined in response of the cells to concanavalin A(Con A) plus phosphatidylserine (PS), phytohemagglutinin (PHA) plus PS or a mixture of low-molecular-weight polymers of P-methoxy-N-methylphenethylamine (compound 48/80). In the response to each of the above stimuli, kanamycin (20mM) or streptomycin (20mM) caused a decrease in the histamine release elicited in the presence of extracellular Ca<2+> (1mM), although streptomycin showed the much higher inhibitory potency than kanamycin. Similarly, streptomycin was much more effective in suppressing compound 48/80-triggered histamine release in the absence of external Ca<2+>. Histamine release in the absence of external Ca<2+> in the response to the lectin plus PS diminished with increasing concentration of kanamycin, and in this respect streptomycin was much less effective. In the response to the lectin plus PS, external Ca<2+> possessed potency to antagonize kanamycin (10mM)- or streptomycin (10mM)-caused inhibition of the histamine release, although more markedly the kanamycin-caused one. Streptomycin and kanamycin inhibit histamine release from mast cells challenged with IgE-directed secretagogue or compound 48/80, and the responsible mechanisms seem to implicate the Ca<2+>-antagonistic action on the stimulus-provoked influx of Ca<2+> and impairment of the cellular events linked to exocytosis.
Single-dose toxicological studies of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether) were conducted. A dispersion of HM-HPMC was administered to rats orally or by dermal application at doses up to 900 mg/kg. After the oral administration, the mean body weight of the 900 mg/kg group on the first day after administration was slightly but significantly lower (P<0.05) than that of the control group, and one rat had loose stools at 30 min. after the administration. No other abnormalities were noted. In the case of dermal application, no abnormalities were observed. No rats died, and no abnormalities in their organs were found by either route. In conclusion, there was no observed toxicity of HM-HPMC after oral or dermal administration at single dose up to 900 mg/kg under the conditions of these studies.
Primary dermal and eye irritation tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether), a new cellulose derivative used as a thickener for topical pharmaceuticals and cosmetics, were conducted in rabbits. A dispersion of HM-HPMC (3%) was applied to intact and abraded skins and reactions were observed. A very slight erythema was observed in both skins and this polymer was categorized as a "mild irritant". In the eye irritation test, with a dispersion of the same concentration, it was categorized as "marginal" in unrinsed eyes and "negative" in rinsed eyes.