504 5. QUINONES 



on renal function is given by those quinones with long side chains, but 

 p-benzoquinone at a higher dosage acts similarly. All the active quinones 

 increase urine volume and the excretion of Na+ and K+, but have little 

 effect on creatinine or 2?-aminohippurate clearance. jj-Benzohydroquinone 

 is not only inactive, but may reduce urine flow and Na+ excretion. It was 

 postulated that the Qq analogs compete with the natural Qjq and thus in- 

 hibit a phase of electron transport associated with Na+ resorption. Phthiocol 

 does not markedly effect renal processes and somewhat reduces urine flow 

 and Na+ excretion (Strickler and Kessler, 1963). 



The Na+ transport across frog skin is inhibited by 0.01-0.1 mM p-henzo- 

 quinone although the respiration is hardly altered, and this effect seems to 

 be irreversible (Fuhrman, 1952). Various oxidants and reductants, in- 

 cluding ?)-benzoquinone, have the property of modifying Na+ transport and 

 the short-circuit current, but the mechanism is not clear (Eubank et al., 

 1962). Menadione at 0.04 milf first causes a transient increase in the short- 

 circuit current and trans-skin potential, but this is followed by an exponen- 

 tial decrease in both (Wang and Koblick, 1959). Since menadione is an 

 effective inhibitor of choline acetylase, it was assumed that this is the 

 mechanism for the depression of Na+ transport, but no direct evidence for 

 this site of action was presented. Taylor et al. (1952) propose that inhibitors 

 of choline acetylase and cholinesterase promote a loss of K+ from erythro- 

 cytes, the former by facilitating K+ efflux and the latter by inhibiting K+ 

 influx. Menadione at 0.1-1 mM causes a loss of erythrocyte K+ and a pro- 

 gressive degree of hemolysis. At 1 mM the rate of K+ is 4 times greater 

 than normal but cholinesterase is inhibited only 16%, while glucose utili- 

 zation is reduced around 50%, so it is difficult to say anything about the 

 site of action, especially since other changes, such as formation of methemo- 

 globin and loss of GSH, probably also occur. 



Inflammatory Reaction 



In view of the relationship between the reaction of SH groups and in- 

 flammation, it is interesting to determine whether the quinones share the 

 irritant effects of the arsenicals, iodoacetate, and other SH reagents. The 

 potent bacteriostatic 3,5-dimethoxytoluquinone does not irritate when 

 instilled into rabbit eyes at 0.81-16 mM (Glock et al., 1945), but a number 

 of naphthoquinones are irritant to the conjunctiva at 5%, which is so high 

 a concentration (250-300 mM) that the results are not very significant 

 (Kligman and Rosensweig, 1948). The ocular reaction to p-benzoquinone 

 was thoroughly studied by Estable (1948), who applied it in physiological 

 saline to rabbit eyes. Concentrations of 0.92-1.84 mM applied daily for 

 several days produce sensory reactions but no inflammation, whereas a 

 concentration of 9.2 mM produces an intense conjunctivitis, vasodilatation, 

 and edema, which disappear in several days. The industrial problem of 



