Reduction of Saltiness and Bitterness After a Chlorhexidine Rinse

Paul A.S. Breslin 0 Christopher D. Tharp 0 0 Monell Chemical Senses Center , 3500 Market St, Philadelphia, PA 19104 , USA Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute chlorhexidine on taste has not been investigated. The purpose of the present study was to examine the effect of acute chlorhexidine rinses on taste intensity and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All stimuli were first matched for overall intensity so the effects of chlorhexidine would be directly comparable across compounds. As a control treatment, the bitter taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects participated in four experimental conditions: a pre-test, a quinine treatment, a chlorhexidine treatment, and a post-test condition, while rating total taste intensity and taste qualities in separate test sessions. Relative to the quinine treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and NH4Cl, and not to significantly affect the tastes of sucrose, monosodium glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses relative to water rinses, but were only marginally suppressed relative to quinine rinses. Potential mechanisms are discussed. - Introduction Psychophysical studies using pharmacological blockers of specific taste qualities (e.g. bitterness or sweetness) hold the potential to provide insight into both the type and number of transduction mechanisms. For this technique to highlight a particular component of taste physiology, two prerequisites must be met. First, the agent must specifically block a taste quality or qualities and not taste in general. Second, the pharmacological agent must have a known biochemical action that could be effective on taste physiology. The best example of specific taste blockade is sodiumspecific taste reduction in some rodents that are exposed orally to the compound amiloride HCl (Halpern, 1998). Amiloride was initially targeted as a candidate for blocking salt taste because: (i) it blocks selected epithelial sodium channels in the kidney and elsewhere (Sonnenberg et al., 1987; Kopp et al., 1998) and (ii) it was hypothesized that these channels mediated salt taste (Schiffman et al., 1983; Heck et al., 1984). Subsequent non-human studies have supported this hypothesis in some species/strains of rodents (Bernstein and Hennessy, 1987; Hill et al., 1990; McCutcheon, 1991; Spector et al., 1996; Harada et al., 1997; Miyamoto et al., 1998; Roitman and Bernstein, 1999), but not others (Ninomiya et al., 1989; Tonosaki and Funakoshi, 1989; Gannon and Contreras, 1995; Miyamoto et al., 1998 1999). For a review see Halpern (Halpern, 1998). In one of the more elegant uses of taste blockers, rats not only failed to distinguish among NaCl and KCl solutions after oral amiloride treatment, but also came to respond to NaCl solutions, in taste guided instrumental responses, as if they tasted like KCl (Spector et al., 1996). From this we can infer that amiloride interferes with an NaCl transduction mechanism that is critical to the recognition of NaCl (e.g. the amiloride-sensitive sodium channel), but does not greatly impede the recognition of KCl. Furthermore, in these animals, NaCl appears also to stimulate the same or a similar mechanism as does KCl, which is largely unaffected by amiloride. The salty taste of sodium salts in humans, however, is not blocked by amiloride, as appears to be the case with several strains/species of rodent, e.g. mice (Halpern, 1998). In humans, initial reports suggested that topical amiloride altered the taste of NaCl, partially decreasing its intensity on the tip of the tongue (Schiffman et al., 1983; McCutcheon, 1992; Tennissen, 1992; Smith and Ossebaard, 1995; Tennissen and McCutcheon, 1996; Anand and Zuniga, 1997). Subsequent studies showed that while amiloride does reduce the overall perceived intensity of NaCl, amiloride does not reduce the perceived saltiness. Rather, amiloride was reported to decrease the subtle sour sidequality of NaCl (Ossebaard and Smith, 1996, 1997; Ossebaard et al., 1997; Halpern and Darlington, 1998). Thus, despite the ability of amiloride to block the unique characteristics of sodium taste in some rodents, it does not have this effect in humans. We believe, however, that Schiffmans (Schiffman et al., 1983) hypothesis that salty taste transduction in mammals occurs via the direct passage of cations into taste cells through cation channels is true of humans as well, although the human salty taste channel remains to be characterized. If amiloride does not selectively block salty taste in humans, are there any other pharmacological substances that might block saltiness? There are reports that chronic use of the topical oral disinfectant and anti-gingival agent, chlorhexidine (at 0.120.2%), specifically reduces the salty taste of NaCl (Lang et al., 1988) or both the salty taste of NaCl and the bitter taste of quinine HCl (Helms et al., 1995). Whether these specific effects might also be observed with an acute chlorhexidine oral rinse is the focus of the present paper. Since previous reports showed that chlorhexidine decreased the saltiness of NaCl and the bitterness of quinine, we included three salts (of varying cation) and three bittertasting compounds, as well as a sweetener (sucrose), an umami/savory stimulus (glutamic acid, sodium saltMSG), both organic and inorganic sour stimuli (citric and hydrochloric acid) and water in the stimulus array. All stimuli were matched for total intensity in order to make valid comparisons across compounds, since in most cases taste blockers are more effective on weaker taste stimuli and less effective on stronger stimuli. In addition, since 0.12% chlorhexidine has a very strong bitter taste, a bitter-tasting control compound that cross-adapts the bitterness of chlorhexidine was necessary. The purpose of this experiment was to identify a bitter tasting compound that (i) could be matched in intensity to 0.12% chlorhexidine and (ii) cross-adapts the bitterness of chlorhexidine. Pilot testing suggested that quinine HCl would cross-adapt chlorhexidine digluconate, so the experiment focused on this bitter-tasting compound as a control. We wished to obtain a control-treatment stimulus that would cross-adapt chlorhexidine because chlorhexidine, in previous reports, may have reduced bitterness or saltiness because of cross-adaptation effects rather than its pharmacological properties. Therefore, a bitter control compound was desired that possessed similar cross-adaptation properties to chlorhexidine. Materials and methods Thirteen non-smoking volunteers (mean age 27 3.4 years) participated in the stud (...truncated)