Gemfibrozil, a lipid‐lowering drug, reduces anxiety, enhances memory, and improves brain oxidative stress in d‐galactose‐induced aging mice

Abstract

Gemfibrozil (GFZ) is a lipid‐lowering drug with several other effects, such as antioxidant and anti‐inflammatory activities. In the current study, chronic d‐galactose treatment (d‐gal, 150 mg/kg/day; i.p., 6 weeks) induced a model of accelerated aging in male mice and was used to study the behavioral, anti‐oxidative, and neuroprotective effects of GFZ (100 mg/kg/day; p.o.). Anxiety‐like behaviors were assessed using the elevated plus‐maze while working memory was measured by spontaneous alternation in a Y‐maze. Brain oxidative stress was determined by measuring malondialdehyde (MDA) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Neuropathological evaluation of the brain with hematoxylin–eosin and Masson's trichrome staining was also performed. The results demonstrated that the anxious‐like phenotype and the cognitive impairments observed in d‐gal‐treated mice could be prevented in those animals coadministered with GFZ. Besides, the decrease in SOD and GPx antioxidant enzymatic activities and increase of MDA levels were also prevented in the brains of d‐gal plus GFZ treated mice. Preliminary hematoxylin–eosin staining also suggested neuroprotective effects of GFZ. The results of Masson's trichrome staining showed no evidence of fibrosis in brain sections of different experimental groups. The current data provide novel insights into GFZ in the d‐galactose‐induced aging mouse model that open promising future research lines to determine inflammatory mediators and cell signaling underlying these effects.

Effect of sacubitril/valsartan on cognitive impairment in colchicine‐induced Alzheimer's model in rats

“…Valsartan can improve cognitive performance initially due to its high antioxidant and anti‐inflammatory properties, but it can also produce a considerable decrease in Aβ levels in the long run because oxidative stress and neuroinflammation are important causes of Aβ buildup [30, 45, 46]. This might explain why valsartan, in our study, was able to improve the cognitive performance of the animals by improving oxidative stress and inflammation with only slightly but nonsignificant reduction in Aβ level.…”

Gemfibrozil, a lipid‐lowering drug, improves hepatorenal damages in a mouse model of aging

“…PPAR-α is a target receptor for GFZ and different actions of GFZ are medicated through this mechanism, including both antihyperlipidemic role and non-hyperlipidemic function [25]. Our previous work [12] investigated the possible neuroprotective effects of GFZ in a D-gal-induced model. The results demonstrated that GFZ diminishes the anxiety-like behavior and improves the memory functions and oxidative stress in mice treated with chronic D-galactose [12].…”

“…Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on PPAR‐α and is effective for hypertriglyceridemia and mixed dyslipidemia [11]. Beyond its standard indication, GFZ has attracted the researcher's attention for its antioxidant and anti‐inflammatory properties [12]. The related mechanisms include blocking the inflammatory mediator such as tumor necrosis factor alpha (TNF‐α) or interleukin‐1 beta (IL‐1β) and improving the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, malondialdehyde (MDA), and free radical's reduction.…”

“…Besides, the studies indicate that GFZ is a neuroprotective agent with significant efficacy against major depressive disorder and Parkinson's disease via PPARα signaling and modulation of brain-derived neurotrophic factor or stimulating glial-derived neurotrophic factor in astrocytes. This medication also improves memory and diminishes anxiety in animals with aging [12,16,17]. Moreover, GFZ plays anti-atherogenic actions via blocking the inflammation [18] and through these properties may be considered as an attractive agent for inhibiting the aging process.…”

Inhibitory effects and molecular mechanisms of ginsenoside Rg1 on the senescence of hematopoietic stem cells

“…Multiple factors have been reported to contribute to the senescence of HSCs, including DNA damage, reactive oxygen species (ROS), epigenetic changes, loss of polarity, and extracellular factors. It is well accepted that accumulation of DNA damage and oxidative stress can induce cell cycle arrest and cellular senescence [29][30][31][32]. Senescent HSCs have shown widespread DNA damage signatures, such as γ-H2AX foci [22].…”