Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

Liu, Chan-Min; Ma, Jie-Qiong; Sun, Yangying

doi:10.1016/j.taap.2011.11.015

Cited by 131 publications

(122 citation statements)

References 81 publications

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“…Notably, the higher dose of CM (10 ml/kg) afforded a marked lowering of BUN (55%), creatinine (49.9%), renal kim-1 (47.4%) and NGAL levels (57.9%) as compared to the 5-FU group. These favorable effects were similar to those provoked by QRC, a reference antioxidant agent with marked reno-protective actions [6, 9]. To a lesser extent, the lower dose of CM (5 ml/ kg) displayed marginal alleviation of these nephrotoxicity markers.…”

Section: Resultssupporting

confidence: 60%

“…An intimate pathway linked to the apoptotic cell death is the phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt) pathway which can be modulated by several renal toxicants. PI3K/Akt has been reported to control cellular survival signals via interaction with the Bcl-2 family [8, 9]. Akt has also been linked to renal NO production through activation of the endothelial nitric oxide synthase (eNOS) [10].…”

Section: Introductionmentioning

confidence: 99%

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Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Arab

Salama

Maghrabi

2018

Cell Physiol Biochem

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Background/Aims: The clinical utility of 5-fluorouracil (5-FU) is limited by its nephrotoxicity. Camel milk (CM) has previously displayed beneficial effects in toxicant-induced nephropathies. The current study aimed to investigate the potential of CM to attenuate 5-FU-induced nephrotoxicity in rats. Methods: Renal tissues were studied in terms of oxidative stress, inflammation and apoptosis. The levels of renal injury markers, inflammatory cytokines along with NOX-1, Nrf-2 and HO-1 were assessed by ELISA. The expression of MMP-2, MMP-9, NF-κBp65, p53, Bax and PCNA were detected by Immunohistochemistry. To gain an insight into the molecular signaling mechanisms, we determined the effect of CM on MAPKs, NF-κB and PI3K/Akt/eNOS pathways by Western blotting. Results: CM lowered 5-FU-triggered increase of creatinine, BUN, Kim-1 and NGAL renal injury biomarkers and attenuated the histopathological aberrations. It suppressed oxidative stress and augmented renal antioxidant armory (GSH, SOD, GPx, TAC) with restoration of NOX-1, Nrf-2 and HO-1 levels. CM also suppressed renal inflammation as indicated by inhibition of MPO, TNF-α, IL-1β, IL-18 and MCP-1 proinflammatory mediators and downregulation of MMP-2 and MMP-9 expression with boosting of IL-10. Regarding MAPKs signaling, CM suppressed the phosphorylation of p38 MAPK, JNK1/2 and ERK1/2 and inhibited NF-κB activation. For apoptosis, CM downregulated p53, Bax, CytC and caspase-3 proapoptotic signals with enhancement of Bcl-2 and PCNA. It also enhanced PI3K p110α, phospho-Akt and phospho-eNOS levels with augmentation of renal NO, favoring cell survival. Equally important, CM preconditioning enhanced 5-FU cytotoxicity in MCF-7, HepG-2, HCT-116 and PC-3 cells, thus, justifying their concomitant use. Conclusion: The current findings pinpoint, for the first time, the marked renoprotective effects of CM that were mediated via ROS scavenging, suppression of MAPKs and NF-κB along with activation of PI3K/Akt/eNOS pathway.

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Section: Resultssupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Arab

Salama

Maghrabi

2018

Cell Physiol Biochem

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“…Caspase-3 is one of the key proteins involved in apoptosis, and CC3 is an activated form of caspase-3 [22,23]. Following exposure of cardiomyocytes to nicotinamide (2.5, 5, 10, or 20 mmol/l) for 16 h, cell death was accessed by examining protein expression of RIP and CC3.…”

Section: Resultsmentioning

confidence: 99%

Nicotinamide Pretreatment Protects Cardiomyocytes against Hypoxia-Induced Cell Death by Improving Mitochondrial Stress

et al. 2012

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Background/Aims: Nicotinamide plays a protective role in hypoxia-induced cardiomyocyte dysfunction. However, the underlying molecular mechanisms remain poorly understood. The purpose of this study was to investigate these and the effect of nicotinamide pretreatment on hypoxic cardiomyocytes. Methods: Cultured rat cardiomyocytes were pretreated with nicotinamide, subjected to hypoxia for 6 h, and then cell necrosis and apoptosis were examined. The effects of nicotinamide pretreatment on hypoxia-induced reactive oxygen species (ROS) formation, antioxidant enzyme expression, nicotinamide adenine dinucleotide (NAD⁺) and nicotinamide adenine dinucleotide phosphate (NADP⁺) levels, adenosine triphosphate (ATP) production and mitochondrial membrane potential were tested to elucidate the underlying mechanisms. Results: Based on the findings that nicotinamide treatment decreased protein expression of receptor-interacting protein (RIP; a marker for cell necrosis) and cleaved caspase-3 (CC3; a marker for cell apoptosis) in normoxic cardiomyocytes, we found that it dramatically reduced hypoxia-induced necrosis and apoptosis in cardiomyocytes. The underlying mechanisms of these effects are associated with the fact that it increased protein expression of superoxide dismutase and catalase, increased intracellular levels of NAD⁺ and ATP concentration, decreased mitochondrial ROS generation and prevented the loss of mitochondrial membrane potential. Conclusion: All of these results indicate that nicotinamide pretreatment protects cardiomyocytes by improving mitochondrial stress. Our study provides a new clue for the utilization of nicotinamide in therapies for ischemic heart disease.

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“…In diabetic mice, puerarin exerted a protective effect on pancreatic β-cell function and survival, which was mediated via the PI3K/Akt pathway (24). Treatment with puerarin effectively inhibited lead-induced apoptosis in the kidney, which was associated with its antioxidant activity and its ability to modulate the PI3K/Akt/endothelial NO synthase signaling pathway (25). Furthermore, puerarin-mediated attenuation of amyloid β-induced microglial apoptosis was dependent upon activation of the PI3K survival pathway and phosphorylation of Akt (26).…”

Section: Discussionmentioning

confidence: 98%

Puerarin prevents tumor necrosis factor-α-induced apoptosis of PC12 cells via activation of the PI3K/Akt signaling pathway

Liang

Xie

2017

Experimental and Therapeutic Medicine

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Abstract. Tumor necrosis factor-α (TNF-α), a potential proinflammatory cytokine, is an important component involved in neuronal apoptosis associated with neuroinflammation in the central nervous system. It has been reported that puerarin possesses pharmacological effects, such as anti-apoptotic, antioxidant, anti-osteoporosis, anti-inflammatory, cardioprotective and neuroprotective actions. The aim of the present study was to explore the effect of puerarin on apoptosis induced by TNF-α (3x10 5 U/l) and its detailed mechanisms in PC12 cells. MTT and flow cytometric assays were performed to evaluate cell cytotoxicity and apoptosis, respectively. An enzymatic assay was used to detect the activity of caspase-3 and caspase-9. Western blot analysis was performed to assess changes in the levels of proteins, including B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, Akt and phosphorylated Akt. The results showed that puerarin (25 and 50 µM) significantly suppressed TNF-α-induced apoptosis in PC12 cells. The TNF-α-induced in crease in the Bax/Bcl-2 ratio was markedly inhibited by pre-treatment with puerarin for 2 h. In addition, puerarin decreased the level of TNF-α-induced cleaved caspase-3. Furthermore, puerarin inhibited the TNF-α-induced decrease in the phosphorylation of Akt, which was abolished by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, suggesting that the PI3K/Akt pathway participated in the suppressive effect of puerarin. Taken together, these findings indicated that puerarin prevented TNF-α-induced apoptosis in PC12 cells via activating of the PI3K/Akt signaling pathway, suggesting that puerarin may be a potential neuroprotective drug in the clinical treatment of neuroinflammation via anti-apoptotic mechanisms.

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Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

Cited by 131 publications

References 81 publications

Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Camel Milk Ameliorates 5-Fluorouracil-Induced Renal Injury in Rats: Targeting MAPKs, NF-κB and PI3K/Akt/eNOS Pathways

Nicotinamide Pretreatment Protects Cardiomyocytes against Hypoxia-Induced Cell Death by Improving Mitochondrial Stress

Puerarin prevents tumor necrosis factor-α-induced apoptosis of PC12 cells via activation of the PI3K/Akt signaling pathway

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