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Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats.
Fundam Clin Pharmacol. 2017 Apr; 31(2):165-173.FC

Abstract

Acetaminophen (APAP) overdose is a common cause of acute liver failure, and beta-blockers are commonly used drugs in clinical practice. This study aimed to evaluate the effect of two different beta-blocker agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male Wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg/day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration. Also, nebivolol increased reduced glutathione (GSH) which was reduced with APAP administration. Moreover, immunohistochemical examination revealed that nebivolol treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced, as compared to APAP group. The protective effects of nebivolol were also verified histopathologically. On the other hand, as compared to APAP group, oral administration of atenolol (50 mg/kg) increased hepatic injury parameters but did not change hepatic NO, MDA, and GSH. In conclusion, this study revealed that nebivolol not atenolol is protective against APAP-induced hepatotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS expression.

Authors+Show Affiliations

Faculty of Medicine, Minia University, Minia, El Minia, 61111, Egypt.Faculty of Medicine, Minia University, Minia, El Minia, 61111, Egypt.Faculty of Medicine, Minia University, Minia, El Minia, 61111, Egypt.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27862262

Citation

Rofaeil, Remon R., et al. "Different Effects of Selective Β1-adrenoceptor Antagonists, Nebivolol or Atenolol in Acetaminophen-induced Hepatotoxicity of Rats." Fundamental & Clinical Pharmacology, vol. 31, no. 2, 2017, pp. 165-173.
Rofaeil RR, Kamel MY, Abdelzaher WY. Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats. Fundam Clin Pharmacol. 2017;31(2):165-173.
Rofaeil, R. R., Kamel, M. Y., & Abdelzaher, W. Y. (2017). Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats. Fundamental & Clinical Pharmacology, 31(2), 165-173. https://doi.org/10.1111/fcp.12253
Rofaeil RR, Kamel MY, Abdelzaher WY. Different Effects of Selective Β1-adrenoceptor Antagonists, Nebivolol or Atenolol in Acetaminophen-induced Hepatotoxicity of Rats. Fundam Clin Pharmacol. 2017;31(2):165-173. PubMed PMID: 27862262.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different effects of selective β1-adrenoceptor antagonists, nebivolol or atenolol in acetaminophen-induced hepatotoxicity of rats. AU - Rofaeil,Remon R, AU - Kamel,Maha Y, AU - Abdelzaher,Walaa Y, Y1 - 2017/02/16/ PY - 2016/03/30/received PY - 2016/08/23/revised PY - 2016/11/10/accepted PY - 2016/11/20/pubmed PY - 2017/6/21/medline PY - 2016/11/19/entrez KW - Acetaminophen KW - Atenolol KW - Nebivolol KW - nitric oxide synthase SP - 165 EP - 173 JF - Fundamental & clinical pharmacology JO - Fundam Clin Pharmacol VL - 31 IS - 2 N2 - Acetaminophen (APAP) overdose is a common cause of acute liver failure, and beta-blockers are commonly used drugs in clinical practice. This study aimed to evaluate the effect of two different beta-blocker agents as nebivolol and atenolol against APAP-induced hepatotoxicity. Male Wistar rats were treated with APAP (2 g/kg/day, p.o.) to induce hepatotoxicity. Our results showed that nebivolol and atenolol reduced heart rate and blood pressure. Nebivolol (5 mg/kg/day, p.o.) for 14 days has a hepatoprotective effect shown by significant decrease in hepatic injury parameters (serum AST and ALT) with significant suppression of hepatic malondialdehyde (MDA) and nitric oxide (NO) which were elevated with APAP administration. Also, nebivolol increased reduced glutathione (GSH) which was reduced with APAP administration. Moreover, immunohistochemical examination revealed that nebivolol treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced, as compared to APAP group. The protective effects of nebivolol were also verified histopathologically. On the other hand, as compared to APAP group, oral administration of atenolol (50 mg/kg) increased hepatic injury parameters but did not change hepatic NO, MDA, and GSH. In conclusion, this study revealed that nebivolol not atenolol is protective against APAP-induced hepatotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS expression. SN - 1472-8206 UR - https://www.unboundmedicine.com/medline/citation/27862262/Different_effects_of_selective_β1_adrenoceptor_antagonists_nebivolol_or_atenolol_in_acetaminophen_induced_hepatotoxicity_of_rats_ L2 - https://doi.org/10.1111/fcp.12253 DB - PRIME DP - Unbound Medicine ER -