Donepezil protects glycerol-induced acute renal failure through the cholinergic anti-inflammatory and nitric oxide pathway in rats

Sun, Guodong; Wang, Jialei; Wang, Pan; Ren, Haiyun; Yue, Yuedong; Song, Zhiyong; Fu, Xiangyu

doi:10.1080/08923973.2020.1835950

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…Moreover, the renoprotective effect of silymarin can be attributed to its antiinflammatory activity by inhibiting the release of proinflammatory cytokines (14,20) , which can be seen in this study by attenuation the renal damage and improving renal function along with reducing inflammatory biomarker levels in renal tissue. These results are compatible with other studies displayed that inflammatory mediators such as TNF-α, IL-1B, IL-6, and NF-κB play a major role in the pathogenesis of rhabdomyolysis-induced AKI after glycerol administration in animals (Suna, 2020;Wang, 2023).…”

Section: Resultssupporting

confidence: 93%

Protective Effect of Silymarin on Attenuating of Rhabdomyolysis -induced Acute Kidney Injury in Animal Models

Mohammed,

Al-Saedi,

Ramadhan

et al. 2023

jmhs

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Acute kidney injury is one of the most serious complications of rhabdomyolysis characterized by an acute loss of renal function. The study aims to investigate the renoprotective effect of silymarin against rhabdomyolysis-induced acute kidney injury in rats. Twenty-four healthy rats were equally divided into three groups: control, induction, and treatment groups. Rats in the control and induction groups received distilled water, while rats in the treatment group received silymarin (50 mg /kg/day p.o) for three consecutive days. On the first day, all rats (except rats of control group) received a single intramuscular injection of glycerol (10 mL/kg, 50% v/v in sterile saline) divided equally into each hind leg for induction of acute kidney injury. On the fourth day of experiment, blood and kidney,s were collected from all rats for biochemical and histopathological assay. Silymarin efficiently attenuated acute kidney injury caused by rhabdomyolysis evidenced by a significant decrease in serum creatinine and blood urea nitrogen(BUN), along with a significant reduction in renal homogenate levels of TNF-α, IL-6, NF-κB, caspase-3, and MDA with a significant increase in GSH level, which was further confirmed by improving renal histological changes when compared to that of induction group. This study found that silymarin has a potential attenuating effect on acute kidney injury due to its antioxidant, anti-inflammatory and antiapoptotic actions.

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Section: Resultssupporting

confidence: 93%

Protective Effect of Silymarin on Attenuating of Rhabdomyolysis -induced Acute Kidney Injury in Animal Models

Mohammed,

Al-Saedi,

Ramadhan

et al. 2023

jmhs

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“…Another study demonstrated that donepezil decreases LPS-induced Iba-1 immunoreactivity in wild-type mice [ 28 ]. In a 1-methyl-4-phenylpyridinium-induced mouse model of PD, donepezil treatment modulates proinflammatory cytokine levels (IL-6, IL-1β, and TNF-α) via inhibition of M1 polarization [ 49 ]. However, whether donepezil modulates LPS-induced microglial cell morphology and migration has not been studied in-depth.…”

Section: Discussionmentioning

confidence: 99%

Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling

Kim

Lee

Park

et al. 2021

IJMS

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The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer’s disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 μM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 μM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Aβ-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.

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“…For example, DNPZ ameliorates memory deficits in high‐fat diet mice by reducing obesity‐related oxidative stress and central inflammation 28 . DNPZ protects against glycerol‐induced acute renal failure in rats via cholinergic anti‐inflammatory and nitric oxide pathways 29 . In the present study, different doses of DNPZ‐treated mice were shown to increase body weight and colon length, reduce DAI scores, and improve colon tissue damage, which was partly accounting for the anti‐inflammatory activity of DNPZ against UC, evidenced by the reduced levels of TNF‐α, IL‐6 and IL‐1β in the serum and intestine of mice following DNPZ treatment.…”

Section: Discussionmentioning

confidence: 99%

Donepezil attenuates inflammation and apoptosis in ulcerative colitis via regulating LRP1/AMPK/NF‐κB signaling

Li,

Zhang,

Chen

et al. 2023

Pathology International

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This article focuses on the specific effects and mechanisms of donepezil (DNPZ) hydrochloride on inflammation and apoptosis in ulcerative colitis (UC). In vivo and in vitro models of UC were established using dextran sodium sulfate (DSS)‐induced mice and NCM460 cells, respectively. Following oral administration of DNPZ, body weight, disease activity index (DAI) scores and colon lengths of mice were recorded. Histopathological damage was detected employing hematoxylin and eosin (H&E) staining. Inflammatory factors were tested using enzyme‐linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction, respectively. Apoptosis was estimated utilizing terminal deoxynucleotidyl transferase dUTP nick‐end labeling and western blot. Low‐density lipoprotein receptor‐related protein 1 (LRP1)/AMP activated protein kinase (AMPK)/nuclear factor‐κB (NF‐ κB) signaling proteins were detected utilizing western blot. NCM460 cell viability was assessed by cell counting kit (CCK)‐8. We found that DNPZ partially restored body weight, reduced DAI scores and attenuated intestinal pathological damage in DSS‐induced mice. Additionally, inflammatory factors decreased significantly after DNPZ treatment, accompanied by reduced apoptosis level. Phosphorylation (p)‐AMPK increased and p‐p65 decreased after DNPZ treatment, whereas LRP1 knockdown showed the opposite effect. Moreover, DNPZ treatment greatly restored NCM460 cell viability after DSS stimulation. DNPZ attenuated DSS‐induced inflammation and apoptosis in NCM460 cells, which was reversed by LRP1 knockdown. In summary, DNPZ hydrochloride attenuates inflammation and apoptosis in UC via LRP1/AMPK/NF‐κB signaling.

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Donepezil protects glycerol-induced acute renal failure through the cholinergic anti-inflammatory and nitric oxide pathway in rats

Cited by 10 publications

References 39 publications

Protective Effect of Silymarin on Attenuating of Rhabdomyolysis -induced Acute Kidney Injury in Animal Models

Protective Effect of Silymarin on Attenuating of Rhabdomyolysis -induced Acute Kidney Injury in Animal Models

Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling

Donepezil attenuates inflammation and apoptosis in ulcerative colitis via regulating LRP1/AMPK/NF‐κB signaling

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