ConclusionsConclusions Despite the complexity Despite the complexity of causal models, measures can be of causal models, measures can be developed that will help improve clinicians' developed that will help improve clinicians' communication with patients and communication with patients and understanding of help-seeking understanding of help-seeking behaviours. behaviours.
The risk presented by β-blockers on aquatic organisms remains uncertain, particularly given the enantiospecific differences in toxicity of chiral β-blockers. In this study, the toxicity of two β-blockers, propranolol and metoprolol, was determined. The 96-h LC50 of propranolol in the zebrafish larvae was 2.48 mg/L, whereas 50 mg/L metoprolol did not result in death. Both β-blockers decreased the heart rate and hatching rate and increased the mortality of the zebrafish embryos. Among these indicators, the heart rate was the most sensitive. However, the acute larval and embryo toxicity results displayed no enantioselectivity. Additionally, the transcriptional response of the genes encoding the β-adrenergic receptors and those involved in other physiological processes, including the antioxidant response, detoxification, and apoptosis, in zebrafish larvae exposed to the β-blockers was examined. Although the changes in gene transcription were fairly minor, significant enantioselectivity was observed for β-blockers, suggesting that the transcriptional response was more sensitive for the evaluation of enantiospecific toxicity. Based on these results, the pharmaceutical drugs were not expected to pose a risk to fish; however, this conclusion should not be considered final. These results also demonstrated that the enantiospecific toxicity of chiral β-blockers should be investigated when performing an ecological risk assessment.
Labetalol hydrochloride (LHCl), an
α- and β-adrenoreceptor
blocker, is widely used for the treatment of hypertension as well
as angina pectoris. Previous reports have demonstrated the adverse
events during clinical application of LHCl, such as liver injury and
acute renal failure. The present study aimed to investigate metabolic
activation of LHCl to initiate the elucidation of the mechanisms of
its liver toxicity. One glutathione (GSH) conjugate was detected in
rat and human primary hepatocytes as well as bile of rats after exposure
to LHCl. The GSH conjugate was chemically synthesized and characterized
by Q-TOF and 1H NMR. Pretreatment of 2,6-dichloro-4-nitrophenol
(DCNP), a broad-spectrum sulfotransferase (SULT) inhibitor, significantly
attenuated the formation of the GSH conjugate in LHCl-treated hepatocytes
and animals, indicating the participation of SULTs in metabolic activation
of LHCl. Moreover, pretreatment with DCNP displayed significant protection
against the observed cytotoxicity in rat primary hepatocytes, which
suggests a correlation of the bioactivation of LHCl mediated by SULTs
with LHCl-induced hepatotoxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.