Repositioning Perindopril for Mitigation of Methotrexate-Induced Hepatotoxicity in Rats DOI Creative Commons

Hanan Abdelmawgoud Atia,

Hemat A. Elariny, Marwa H. Abdallah

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 358 - 358

Опубликована: Март 2, 2025

Background/Objectives: Methotrexate is a folate antagonist that has proven efficacy as an anticancer and immunomodulatory agent. However, the possible incidence of overt hepatotoxicity represents challenge for its clinical use. Up till now, no single remedy been considered effective solution to this important adverse effect. Perindopril angiotensin-converting enzyme inhibitor widely used treatment hypertension. Due involvement renin–angiotensin system in pathogenesis methotrexate-elicited hepatotoxicity, investigating perindopril condition may be particular interest. The current work aimed at evaluation potential effects rat model methotrexate-induced tried precisely determine molecular mechanisms represent basis these effects. Methods: In male Wistar rats, different doses were evaluated level biochemical measurements morphological examination. Results: Oral administration methotrexate-injected rats exhibited dose-dependent significant improvement daily food intake; restoration functions hepatocytes; potentiation antioxidant defense mechanisms; abrogation signaling pathways involved liver inflammation, apoptosis, fibrosis; enhancement AMPK/mTOR-driven autophagy when compared animals received only methotrexate injection. These events reflected appearance studied groups. Conclusions: This study presents promising mitigation hepatotoxic occur consequence with methotrexate.

Язык: Английский

Activation of SIRT1 by SRT1720 Alleviates Dyslipidemia, Improves Insulin Sensitivity and Exhibits Liver-Protective Effects in Diabetic Rats on a High-Fat Diet: New Insights into the SIRT1/Nrf2/NFκB Signaling Pathway DOI Creative Commons
Elsayed A. Elmorsy, Hossam A. Elsisi, Abdullah S. Alkhamiss

и другие.

European Journal of Pharmaceutical Sciences, Год журнала: 2025, Номер 206, С. 107002 - 107002

Опубликована: Янв. 6, 2025

Insulin resistance and diabetes are associated with non-alcoholic fatty liver disease (NAFLD) steatohepatitis (NASH) conditions, which distinguished by metabolic dysfunction, oxidative stress inflammation. Sirtuin 1 (SIRT1), a NAD

Язык: Английский

Процитировано

3
Screening of Gehua Jiejiu Dizhi Decoction Active Components for the Treatment of Alcoholic Fatty Liver Disease and Their Effects of Taxifolin and Genistein on Sirtuin 1/Sirtuin 3-Forkhead Boxo1 Signaling DOI
Yao Zou,

J. Rebecca Liu,

Yi Xu

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Liver ischemia reperfusion injury: Mechanisms, cellular pathways, and therapeutic approaches DOI
Thiago Henrique Oliveira, Gleisy Kelly Neves Gonçalves

International Immunopharmacology, Год журнала: 2025, Номер 150, С. 114299 - 114299

Опубликована: Фев. 16, 2025

Язык: Английский

Процитировано

0
Mitochondrial uncoupling, a new element in pathogenesis of metabolic syndrome: a pilot study DOI Creative Commons
S. S. Voronova, Maria Bograya, Maria Vulf

и другие.

Russian Journal of Immunology, Год журнала: 2025, Номер 28(2), С. 329 - 336

Опубликована: Фев. 16, 2025

Obesity and insulin resistance are the main factors in development of metabolic syndrome (MetS). In patients with MetS, there is an active accumulation free fatty acids liver, which may lead to disturbances homeostasis metabolism hepatocytes, thus resulting mitochondrial dysfunction, oxidative stress, cellular apoptosis. Mitochondrial dysfunction has been extensively studied context pathogenetic features syndrome. However, processes uncoupling remain unclear. (MU) a process associated decrease ATP synthesis reactive oxygen species (ROS) mitochondria. It mediated by proteins from UCP (uncoupling proteins) family, as well ANT (ADP/ATP translocase). “Mild” MU necessary for maintaining normal function, whereas “severe” dysfunction. Thus, aim present study was investigate expression levels SIRT1 V1 deacetylase, transcription PGC-1α, PPAR-α, PPAR-γ that stimulate lipogenesis β-oxidation FFAs, some genes encoding uncouplers ANT2 UCP2 liver MetS. The included two groups, follows: MetS (inclusion criteria: BMI 30 kg/m2, along type 2 diabetes and/or fasting blood glucose 5.5 mmol/L), control group (BMI absence infectious chronic diseases). Biochemical analysis parameters conducted using Furuno CA-180 biochemical analyzer (Furuno Electric Company, Japan) DiaSys test systems (DiaSys Diagnostic Systems, Holzheim, Germany). interest biopsies were assessed quantitative RT-PCR SYBR Green (Evrogen, Russia). significant increase (compared group) level factor found, being de novo increased uncoupler gene. Expression other (SIRT1 V1, UCP2) measured did not show changes. An gene be related both compensatory protective mechanisms, e.g., activation “mild” MU, pathological “strong” MU. Further studies needed effects on (ATP production, ROS generation, stress), directly human tissue, cell cultures. This article presents first time results concerning (ANT2,

Язык: Английский

Процитировано

0
Repositioning Perindopril for Mitigation of Methotrexate-Induced Hepatotoxicity in Rats DOI Creative Commons

Hanan Abdelmawgoud Atia,

Hemat A. Elariny, Marwa H. Abdallah

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 358 - 358

Опубликована: Март 2, 2025

Background/Objectives: Methotrexate is a folate antagonist that has proven efficacy as an anticancer and immunomodulatory agent. However, the possible incidence of overt hepatotoxicity represents challenge for its clinical use. Up till now, no single remedy been considered effective solution to this important adverse effect. Perindopril angiotensin-converting enzyme inhibitor widely used treatment hypertension. Due involvement renin–angiotensin system in pathogenesis methotrexate-elicited hepatotoxicity, investigating perindopril condition may be particular interest. The current work aimed at evaluation potential effects rat model methotrexate-induced tried precisely determine molecular mechanisms represent basis these effects. Methods: In male Wistar rats, different doses were evaluated level biochemical measurements morphological examination. Results: Oral administration methotrexate-injected rats exhibited dose-dependent significant improvement daily food intake; restoration functions hepatocytes; potentiation antioxidant defense mechanisms; abrogation signaling pathways involved liver inflammation, apoptosis, fibrosis; enhancement AMPK/mTOR-driven autophagy when compared animals received only methotrexate injection. These events reflected appearance studied groups. Conclusions: This study presents promising mitigation hepatotoxic occur consequence with methotrexate.

Язык: Английский

Процитировано

0