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Protective Effects of Trimetazidine Against Acetaminophen-Induced Liver Injury in Mice

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Acetaminophen (APAP) overdose accounts for many cases of acute liver injury. The aim of the present study was to explore the possible hepatoprotective effect of trimetazidine, an anti-ischemic antianginal agent, against APAP-induced acute hepatotoxicity. Mice (n = 6) received trimetazidine (10 mg/kg) for seven consecutive days, followed by a single intraperitoneal injection of APAP (750 mg/kg). Mice receiving saline (n = 6) and non-treated APAP group (n = 10) served as controls. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), total proteins and albumin were determined. Hepatic total nitrite/nitrate (NOx) and antioxidant status were assessed and histological analyses were performed. Hepatic levels of interleukin-6 (IL-6) were assayed by ELISA. The hepatic tissue expression of tumor necrosis factor-α (TNF-α) was identified immunohistochemically. Pre-treatment with trimetazidine prevented APAP-induced mortality. It also attenuated APAP-induced liver injury in mice as revealed by significantly inhibiting APAP-induced elevations in serum levels of ALT, AST, LDH, γ-GT and ALP and hepatic malondialdehyde and IL-6 contents. In addition, it significantly ameliorated APAP-induced reductions in serum levels of albumin and total proteins and hepatic levels of reduced glutathione, superoxide dismutase and NOx. Moreover, trimetazidine-treated mice showed reduced hepatic expression of TNF-α compared to APAP group. Trimetazidine effectively preserved tissue morphology as evidenced by histological evaluation. In conclusion, trimetazidine mitigated acute liver injury induced by APAP overdose in mice, a hepatoprotective effect which can be attributed to inhibition of oxidative stress and the proinflammatory cytokine TNF-α- and IL-6-dependent inflammation.
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Keywords: ACETAMINOPHEN; ACUTE LIVER INJURY; IL-6; INFLAMMATION; OXIDATIVE STRESS; TNF-α; TRIMETAZIDINE

Document Type: Research Article

Publication date: March 1, 2017

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  • Journal of Pharmaceutical Sciences and Pharmacology is being launched to address the disconnect among different research areas related to pharmaceutical sciences and pharmacology. The extreme specialization has resulted in compartmentalization and complete segregation of disciplines related to pharmaceutical sciences. Relating a new development in drug delivery has become difficult to be noticed by the researchers in other related disciplines like the pharmacologists and/or clinicians. The aim of this journal is to publish high quality original research work and broad reviews in all related disciplines relevant to drugs under the same umbrella. Our expectation is that it will help the researchers, scholars and scientists to put their and others' work in the bigger context resulting in enhanced interdisciplinary and integrated research effort. The journal is intended to cover all disciplines and challenges in science, technology and engineering that contribute to the development of new improved drug molecules and their uses including pharmaceutical aspects.
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