Kallikrein/kinin protects against gentamicin-induced nephrotoxicity by inhibition of inflammation and apoptosis

Bledsoe, Grant; Crickman, Sarah; Mao, Jenny T.; Xia, Chun‐Fang; Murakami, Hideyuki; Chao, Lee; Chao, Julie

doi:10.1093/ndt/gfi225

Cited by 100 publications

(76 citation statements)

References 18 publications

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“…This indeed appears to be the case, given that subduing Klk action (using B2 receptor blockers) rendered BALB/c control mice AIGN susceptible, while the administration of BK ameliorated nephritis in AIGN-susceptible 129/SvJ mice ( Figure 3). These findings resonate well with previous genetic and pharmacological studies that also reveal a renoprotective role for Klk and BKs in nephritis following other insults, including hypertension, ischemic stroke, salt imbalance, and diabetes (26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Previous studies suggest that Klk may be playing a protective role in nephritis by modulating several different parameters, including local blood pressure, the inflammatory milieu, redox balance, and/or signaling within various cell types (25,26,31,(36)(37)(38)(39).…”

Section: Figuresupporting

confidence: 89%

“…Importantly, this gene complex is encoded within an interval on chromosome 7 that had previously been associated with spontaneous lupus nephritis (14)(15)(16)(17)(18)(19)(20)(21). Kallikreins constitute a multigene family of serine esterases with a wide spectrum of biological functions (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). These reported functions include the regulation of inflammation, apoptosis, redox balance, and fibrosis within the kidneys, as well as local blood pressure.…”

Section: Figurementioning

confidence: 99%

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Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

Li²,

et al. 2009

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. 16 The collaborative groups are detailed at the end of this article.Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.

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Section: Figuresupporting

confidence: 89%

Section: Figurementioning

confidence: 99%

Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

Li²,

et al. 2009

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“…[4][5][6] Accumulating evidence has also suggested that apoptosis, necrosis, and oxidative stress augmentation could be associated with the GM-induced nephrotoxicity. 7,8 Thus, a promising therapeutic approach may be required to curb or protect renal damage against antibiotics adverse effects, and GM-induced nephrotoxicity is an excellent animal model for studying pathogenesis and therapeutic approach development. 9 In the past few years, much attention has been laid on the role of naturally occurring dietary substances for the control and management of various acute and chronic diseases, one such compound berberine has been used since ancient times for promoting human health.…”

Section: Introductionmentioning

confidence: 99%

Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

et al. 2016

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Background: Gentamicin (GM) is the commonly used antibiotics against Gram-negative infection, but the nephrotoxic potential of drug limit its clinical interest. The aim of this study was to investigate the protective effect of berberine (BER) against GM-induced nephrotoxicity and possible underlying mechanisms. Material and methods: The rats were divided into various group, namely normal, GM-control, GM þ BER (10, 20, and 40 mg/kg). Nephrotoxicity was induced by intraperitoneal administration of GM (120 mg/kg) for 7 consecutive days. BER (10, 20, and 40 mg/kg; p.o.) was also administered for the 7 days. Various biochemical, molecular, and histological parameters were assessed in serum and kidney. Results: GM-administration significantly increased (p < 0.001) the serum creatinine and blood urea nitrogen (BUN) as well as renal malonaldehyde (MDA), nitric oxide (NO) along with Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor-kappa B (NF-KB) renal mRNA expressions. In addition, GM also significantly decreased (p < 0.001) the renal superoxide dismutase (SOD), reduced glutathione (GSH), B-cell lymphoma 2 (Bcl-2) mRNA expression, and mitochondrial enzymes (NADH dehydrogenase and cytochrome c oxidase) activities. Rats treated with BER (20 and 40 mg/kg; p.o.) significantly and dose-dependently (p < 0.05 and p < 0.01) restore the altered levels of antioxidant, inflammatory, apoptosis, AKI markers as well as depleted mitochondrial enzymes. Histopathological abbreviations were also ameliorated by BER administration. Conclusion: Berberine exerts renoprotective effects through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

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“…The present study demonstrated that kallikrein/kinin protects against hypertensive renal injury by inhibiting apoptosis in the kidney. Kallikrein/ kinin directly improves renal function, independent of its effects on blood pressure, by inhibiting apoptosis in multiple animal models, including salt-sensitive rats and gentamicininduced renal injury [20,21] . Our previous study demonstrated that rAAV-mediated HK delivery upregulates the B2 receptor and downregulates angiotension II receptor 1, endothelin receptor A and vasopressin receptor 2 [22] , which could also contribute to the anti-apoptotic effects of the kallikrein/kinin system in hypertensive kidney injuries.…”

Section: Discussionmentioning

confidence: 99%

Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis

Yan

Wang

2009

Acta Pharmacol Sin

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Aim: Overexpression of human tissue kallikrein (HK), mediated by recombinant adeno-associated virus (rAAV), decreased blood pressure in spontaneous hypertensive rats (SHRs) and reduced injury to the heart, aorta and kidney. In this study, we used both an in vivo animal model and in vitro cell culture system to investigate whether rAAV-mediated HK gene therapy protects against organ damage by inhibiting cell apoptosis. Methods: rAAV encoding HK (rAAV-HK) or LacZ (rAAV-lacZ) were delivered as a control to spontaneously hypertensive rats (SHRs) and cultured human embryonic kidney (HEK) 293 cells. Results: Treatment with rAAV-HK decreased cell apoptosis in the target organs of SHRs and also inhibited lipopolysaccharide (LPS)-induced HEK 293 apoptosis. The rAAV-HK delivery system also increased the levels of apoptosis-inhibiting proteins bcl-2 and bcl-x L , and decreased the level of Bax and the activity of caspase 3, two promoters of apoptosis. In addition to its role in the inhibition of apoptosis, rAAV-HK also activated the cell survival and proliferation signaling pathways ERK1/2 and PI3K/AKT. Conclusion: rAAV-mediated HK gene delivery has multiple therapeutic possibilities for treating hypertension, not only by decreasing blood pressure, but also by directly inhibiting end-organ damage.

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Kallikrein/kinin protects against gentamicin-induced nephrotoxicity by inhibition of inflammation and apoptosis

Cited by 100 publications

References 18 publications

Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

Kallikrein genes are associated with lupus and glomerular basement membrane–specific antibody–induced nephritis in mice and humans

Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction

Recombinant adeno-associated virus-mediated human kallikrein gene therapy protects against hypertensive target organ injuries through inhibiting cell apoptosis

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