Bisphenol A inhibits compound action potentials in the frog sciatic nerve in a manner independent of estrogen receptors

Abstract

Although the endocrine disruptor bisphenol A (BPA) is reported to inhibit nerve conduction, the underlying mechanisms are unclear. Therefore, in the present study, we examined the effect of BPA on compound action potentials (CAPs) recorded from the frog sciatic nerve using the air-gap method. Treatment of the sciatic nerve with BPA (0.5 mM) for 20 min reduced the peak amplitude of the CAP by approximately 60% in a partially reversible manner. The reduction in the CAP peak amplitude was concentration-dependent, with a half-maximal inhibitory concentration (IC50) value of 0.31 mM. This effect of BPA was unaffected by an estrogen-receptor antagonist, 4-hydroxytamoxifen, which by itself reduced CAP peak amplitude, with an IC50 value of 0.26 mM (comparable to that of BPA). The natural estrogen 17β-estradiol, at the highest dissolvable concentration (0.05 mM), had an effect similar to that of BPA. The IC50 value of BPA was comparable to those of some local anesthetics in inhibiting frog CAPs. Our findings suggest that BPA inhibits nerve conduction in a manner independent of estrogen receptors. This action of BPA may underlie, at least in part, the neurotoxicity of the compound.

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

“…IC 50 values for lidocaine and ropivacaine (0.74 and 0.34 mM, respectively) in the frog sciatic nerve were not so different from those (0.28 mM for both lidocaine and ropivacaine) for fast-conducting CAPs in the rat sciatic nerve [236]. Moreover, an amide-type local anesthetic prilocaine also reversibly reduced frog sciatic nerve CAP peak amplitudes; this activity was concentration-dependent in a range of 0.01-5 mM with an IC 50 value of 1.8 mM [26].…”

“…CAPs were effectively inhibited by 2,6-dichlorodiphenylamine and N-phenylanthranilic acid that are not NSAIDs while being similar in chemical structure to NSAIDs having two benzene rings (see Figures 4Aa and 4Ba in [21]). CAPs were also depressed by bisphenol A that have two benzene rings that bind a hydrophilic group such as -OH [26].…”

“…A non-amide-and non-ester-type local anesthetic pramoxine also reduced frog sciatic nerve CAP peak amplitudes with a slow recovery to those before its application. This pramoxine activity was concentration-dependent in a range of 0.001-1 mM with an IC 50 value of 0.21 mM [26]. Table 6 summarizes IC 50 values for frog sciatic nerve fast-conducting CAP inhibitions produced by local anesthetics together with those for rat sciatic nerve CAPs and voltage-gated Na + channels.…”

“…The chemical structures of local anesthetics tested are shown in Figure 4 in [25]. [22,71] Other Type Pramoxine 0.21 [26] Here, when IC 50 values are not available, it is partly shown for comparison how CAP and channel current amplitudes are reduced by drugs, where % value indicates the extent of the reduction at the concentration shown in parentheses.…”

Analgesics and analgesic adjuvants inhibiting nerve conduction in the frog sciatic nerve —local anesthetics, opioids, α₂ adrenoceptor agonists, antiepileptics, antidepressants and NSAIDs

“…CAP の振幅を減少させた。その振幅を半分減 少させる濃度である half-maximal inhibitory concentration (IC50)値は，それぞれ 2.2, 0.80, 0.013, 1.8, 0.74, 0.34, 0.23, 0.21 mM で あ っ た (Table 1) 19,24,34,35,48,49) Fig.3-A Fig.4-A 6,40,51,52) ，同じ条件下でのその効率の比較は 調べられていなかった。それらの化学構造は， トラゾドンを除き，アミン基を持つと同時にベ ンゼン環を含んでおり，局所麻酔薬と似ている ことから( Fig.1-B 参照) Fig.6-A, B, C, D 20,30,38,48)…”