Agmatine attenuates rhabdomyolysis-induced acute kidney injury in rats in a dose dependent manner

Sharawy, Maha H.; Abdelrahman, Rehab S.; El‐Kashef, Dalia H.

doi:10.1016/j.lfs.2018.07.019

Cited by 42 publications

(22 citation statements)

References 49 publications

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“… 7 , 42 NGAL, stress protein, belongs to the lipocalin superfamily and is considered an early diagnostic marker for AKI. 43 In agreement with Sharawy et al 43 a significant increment was found in its level in the glycerol-treated group that ensures renal damage.…”

Section: Discussionsupporting

confidence: 80%

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Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats

Albrakati

Alsharif

Alzahrani

et al. 2021

IJN

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Purpose Selenium nanoparticles (SeNPs) have recently gained much attention in nanomedicine applications owing to their unique biological properties. Biosynthesis of SeNPs using nutraceuticals as lycopene (LYC) maximizes their stability and bioactivities. In this context, this study aimed to elucidate the renoprotective activity of SeNPs coated with LYC (LYC-SeNPs) in the acute kidney injury (AKI) model. Methods Rats were divided into six groups: control, AKI (glycerol-treated), AKI+sodium selenite (Na 2 SeO 3 ; 0.5 mg/kg), AKI+LYC (10 mg/kg), AKI+LYC-SeNPs (0.5 mg/kg) and treated for 14 days. Results Glycerol treatment evoked significant increases in rhabdomyolysis-related markers (creatine kinase and LDH). Furthermore, relative kidney weight, Kim-1, neutrophil gelatinase-associated lipocalin (NGAL), serum urea, and creatinine in the AKI group were elevated. Glycerol-injected rats displayed declines in reduced glutathione level, and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, paralleled with downregulations in Nfe2l2 and Hmox-1 expressions and high renal MDA and NO contents. Glycerol-induced renal inflammation was evident by rises in TNF-α, IL-1β, IL-6, and upregulated Nos2 expression. Also, apoptotic (elevated caspase-3, Bax, and cytochrome-c with lowered Bcl-2) and necroptotic (elevated Pipk3 expression) changes were reported in damaged renal tissue. Co-treatment with Na 2 SeO 3 , LYC, or LYC-SeNPs restored the biochemical, molecular, and histological alterations in AKI. In comparison with Na 2 SeO 3 or LYC treatment, LYC-SeNPs had the best nephroprotective profile. Conclusion Our findings authentically revealed that LYC-SeNPs co-administration could be a prospective candidate against AKI-mediated renal damage via antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic activities.

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Section: Discussionsupporting

confidence: 80%

“…2 Additionally, iNOS triggers the generation of reactive nitrogen species that also interact with superoxide anions to produce peroxynitrite radical and enhance the production of pro-inflammatory cytokines. 43 …”

Section: Discussionmentioning

confidence: 99%

Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats

Albrakati

Alsharif

Alzahrani

et al. 2021

IJN

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“…Agmatine not only prevented the LPS-induced elevation in mRNA expression of iNOS but also decreased the activity of iNOS induced by LPS, thereby inhibiting the production of nitrite 38,39 . In addition, it was also found in acute kidney injury models that agmatine decreased the levels of renal NO and iNOS 40 . Therefore, based on the combination of our results and the published literature, we speculate that AGMAT promotes iNOS expression and NO production by hydrolyzing agmatine, thereby promoting the development of lung adenocarcinoma.…”

Section: Discussionmentioning

confidence: 91%

Agmatinase promotes the lung adenocarcinoma tumorigenesis by activating the NO-MAPKs-PI3K/Akt pathway

et al. 2019

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Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. There is an urgent need to uncover the pathogenic mechanism to develop new treatments. Agmatinase (AGMAT) expression and its association with clinicopathological characteristics were analyzed via GEO, Oncomine, and TCGA databases, and IHC staining in human LUAD specimens. An EdU cell proliferation kit, propidiumiodide staining, colony formation, cell migration, and invasion assays, and a xenograft tumor model were used to detect the biological function of AGMAT in LUAD. Furthermore, the expression level of nitric oxide (NO) was detected using a DAF-FMDA fluorescent probe or nitrite assay kit, and further validated with Carboxy-PTIO (a NO scavenger). The roles of three isoforms of nitric oxide synthases (nNOS, eNOS, and iNOS) were validated using L-NAME (eNOS inhibitor), SMT (iNOS inhibitor), and spermidine (nNOS inhibitor). AGMAT expression was up-regulated in LUAD tissues. LUAD patients with high AGMAT levels were associated with poorer prognoses. AGMAT promoted LUAD tumorigenesis in NO released by iNOS both in vitro and in vivo. Importantly, NO signaling up-regulated the expression of cyclin D1 via activating the MAPK and PI3K/Akt-dependent c-myc activity, ultimately promoting the malignant proliferation of tumor cells. On the whole, AGMAT promoted NO release via up-regulating the expression of iNOS. High levels of NO drove LUAD tumorigenesis via activating MAPK and PI3K/Akt cascades. AGMAT might be a potential diagnostic and therapeutic target for LUAD patients.

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“…As a key transcription regulator of inflammation, NF-κB promotes the expression of pro-inflammatory cytokines and adhesion molecules. Both clinical and experimental data confirmed the elevation and activation of NF-κB in a variety of renal inflammatory disorders [12, 30, 31]. Meanwhile, it was found that NGAL could be induced to overexpress by NF-κB as a member of lipocalin superfamily and biomarker of AKI [32].…”

Section: Discussionmentioning

confidence: 93%

2-methylquinazoline derivative F7 as a potent and selective HDAC6 inhibitor protected against rhabdomyolysis-induced acute kidney injury

et al. 2019

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Histone deacetylases 6 (HDAC6) has been reported to be involved in the pathogenesis of rhabdomyolysis-induced acute kidney injury (AKI). Selective inhibition of HDAC6 activity might be a potential treatment for AKI. In our lab, N-hydroxy-6-(4-(methyl(2-methylquinazolin-4-yl)amino)phenoxy)nicotinamide (F7) has been synthesized and inhibited HDAC6 activity with the IC50 of 5.8 nM. However, whether F7 possessed favorable renoprotection against rhabdomyolysis-induced AKI and the involved mechanisms remained unclear. In the study, glycerol-injected mice developed severe AKI symptoms as indicated by acute renal dysfunction and pathological changes, accompanied by the overexpression of HDAC6 in tubular epithelial cells. Pretreatment with F7 at a dose of 40 mg/kg/d for 3 days significantly attenuated serum creatinine, serum urea, renal tubular damage and suppressed renal inflammatory responses. Mechanistically, F7 enhanced the acetylation of histone H3 and α-tubulin to reduce HDAC6 activity. Glycerol-induced AKI triggered multiple signal mediators of NF-κB pathway as well as the elevation of ERK1/2 protein and p38 phosphorylation. Glycerol also induced the high expression of proinflammatory cytokine IL-1β and IL-6 in kidney and human renal proximal tubule HK-2 cells. Treatment of F7 notably improved above-mentioned inflammatory responses in the injured kidney tissue and HK-2 cell. Overall, these data highlighted that 2-methylquinazoline derivative F7 inhibited renal HDAC6 activity and inflammatory responses to protect against rhabdomyolysis-induced AKI.

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Agmatine attenuates rhabdomyolysis-induced acute kidney injury in rats in a dose dependent manner

Cited by 42 publications

References 49 publications

Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats

Using Green Biosynthesized Lycopene-Coated Selenium Nanoparticles to Rescue Renal Damage in Glycerol-Induced Acute Kidney Injury in Rats

Agmatinase promotes the lung adenocarcinoma tumorigenesis by activating the NO-MAPKs-PI3K/Akt pathway

2-methylquinazoline derivative F7 as a potent and selective HDAC6 inhibitor protected against rhabdomyolysis-induced acute kidney injury

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