We show that hypercholesterolemia contributes to oxidative stress injury progression in brain and simvastatin counteracts the cholesterol-induced peroxidation injury in rabbit hippocampus, and we demonstrate for the first time that the simvastatin is a critical role in brain protection and identify HO-1 and other related antioxidant enzymes as molecular target for active redox compounds. Second, our experiments have pointed out an association between statin treatment and a decrease in the risk of having peroxidation damage of brain. The balance effects of simvastatin to ROS and antioxidants enzymes network are most probably due to improved SOD functional activity, increase in GSH-Px, increase in HO-1 expression, and decrease of MDA generation.
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http://dx.doi.org/10.1155/2016/6929306 | DOI Listing |
Drug Deliv Transl Res
March 2025
Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia.
Simvastatin is a potent statin with antioxidant and anti-inflammatory characteristics, often used to treat hyperlipidemia and related cardiovascular disorders. Nonetheless, its therapeutic advantages are limited by poor water solubility and substantial degradation by CYP3A4 enzymes. This research aimed to improve simvastatin's physicochemical characteristics and therapeutic effectiveness by developing 3D-dendritic mesoporous silica nanoparticles as nanocarriers.
View Article and Find Full Text PDFToxicol Mech Methods
March 2025
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) inhibitors, commonly known as statins, are drugs frequently used in the treatment of hypercholesterolemia and hyperlipidemia. However, the current study has demonstrated that simvastatin induces neurotoxicity and is associated with cellular coenzyme Q (CoQ) depletion. CoQ has a significant role in the mitochondrial electron transport chain (ETC), in addition to being a fundamental lipid-soluble antioxidant.
View Article and Find Full Text PDFArch Biochem Biophys
February 2025
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address:
Chronic pancreatitis (CP), a progressive inflammatory disease characterized by pancreatic tissue destruction and fibrosis, is considered a challenging health burden due to insufficiencies of current management procedures. Autophagy impairment has emerged as a major triggering event in pancreatitis, raising interest in exploring the potential of targeting autophagy as a possible interventional strategy. This study aimed to evaluate the possible ameliorative effect of two autophagy modulators, simvastatin and eugenol, on CP-related perturbations in an arginine-induced rat model.
View Article and Find Full Text PDFMetabol Open
March 2025
Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa, 3886, South Africa.
Dyslipidemia is a prominent pathological feature responsible for oxidative stress-induced cardiac damage. Due to their high antioxidant content, dietary compounds, such as aspalathin and sulforaphane, are increasingly explored for their cardioprotective effects against lipid-induced toxicity. Cultured H9c2 cardiomyoblasts, an in vitro model routinely used to assess the pharmacological effect of drugs, were pretreated with the dietary compounds, aspalathin (1 μM) and sulforaphane (10 μM) before exposure to palmitic acid (0.
View Article and Find Full Text PDFCell Rep Med
February 2025
Renji-Med-X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200127, China; Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address:
The induction of immunogenic cell death (ICD) impedes tumor progression via both tumor cell-intrinsic and -extrinsic mechanisms, representing a robust therapeutic strategy. However, ICD-targeted therapy remains to be explored and optimized. Through kinome-wide CRISPR-Cas9 screen, NUAK family SNF1-like kinase 1 (NUAK1) is identified as a potential target.
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