Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats

Quirós, Yaremi; Blanco-Gozalo, Víctor; Sánchez-Gallego, José I.; López‐Hernández, Francisco J.; Ruiz, Juan; Obanos, María P. Pérez de; López‐Novoa, José M.

doi:10.1016/j.phrs.2016.02.025

Cited by 24 publications

(20 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Protein carbonyl content is a marker for estimating the extent of protein damage in kidney . Increasing these oxidative stress indices can cause morphological and functional changes in the kidney . Consistent with previous studies, we observed that CP increases renal MDA and NO levels and PC content suggesting that CP causes oxidative damage to the lipids and proteins of the kidney.…”

Section: Discussionsupporting

confidence: 90%

Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice

Goudarzi

Khodayar

Tabatabaei

et al. 2017

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

Cyclophosphamide (CP) is widely used in treatment of different cancers. Nephrotoxicity is one of the dose-limiting side effects of CP. This study was carried out to investigate the effect of melatonin (MEL) on CP-induced nephrotoxicity in mice. In this study, 50 Swiss albino mice (20-25 g) were randomly divided into five groups. Mice were pretreated with MEL intraperitoneally (i.p) in doses of 5, 10 and 20 mg/kg for five consecutive days, and CP (200 mg/kg, i.p) was administrated on the 5th day 1 h after the last dose of MEL. Then on day 6, blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidneys were used for histological examination, biochemical assays and real-time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activity were assessed in renal tissue. In addition, the expression of SOD2 and PGx1 was measured using real-time PCR method in renal tissue. Results showed that CP administration significantly increases Cr, BUN, MDA, PC, NO level and MPO activity. It also decreases renal GSH level, SOD, GPx and CAT activity. Pretreatment with MEL (especially 20 mg/kg, i.p.) for 5 days prevented these changes; however, it did not affect the SOD activity. Our results revealed that MEL might be useful for prevention of the nephrotoxicity induced by CP through ameliorative effects on biochemical indices and oxidative stress parameters.

show abstract

Section: Discussionsupporting

confidence: 90%

Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice

Goudarzi

Khodayar

Tabatabaei

et al. 2017

Fundamemntal Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…In the previous investigation, pro-inflammatory cytokines increased expression at the gene and protein levels after GM injection [30]. There are these inflammatory cytokines lead to nephrotoxicity, such as IL-6 and TNF-α.…”

Section: Discussionmentioning

confidence: 84%

The Protective Effect of Sika Deer Antler Protein on Gentamicin-Induced Nephrotoxicity in Vitro and in Vivo

Sun¹,

Yang²,

Ruan³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Sika deer (Cervus nippon Temminck) antler is traditional animal medicine of renal protection in East Asia. This study measured the effect of sika deer antler protein (SDAPR) on gentamicin (GM)-induced cytotoxicity in HEK293 cells, and investigated the effect of SDAPR against GM-induced nephrotoxicity in mice. Methods: HEK293 cells viability and oxidative stress were measured in HEK293 cells while flow cytometry was used for apoptosis analysis. The acute kidney injury biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys-C), were repeatedly measured by ELISA assay. ICR male mice were randomly assigned six groups: Control, GM with vehicle, single SDAPR, GM with SDAPR at three concentrations 50, 100, 200 mg/kg/d, p.o., 10 d. GM was injected for 8 consecutive days (100 mg/kg/d, i.p.). Renal function, oxidative stress and levels of inflammatory factors were measured in vivo. Renal tissues were stained with H&E to observe pathological changes. Results: Pretreatment with SDAPR (0.5-4.0 mg/mL) significantly improved cell viability. Treatment with SDAPR could reduce KIM-1, NGAL and Cys-C activity. SDAPR could improve antioxidant defense and attenuated apoptosis on HEK293 cells. SDAPR also ameliorated GM-induced histopathologic changes, and decreased blood urea nitrogen (BUN) and serum creatinine (Cr). Additionally, SDAPR significantly regulated oxidative stress marker and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) inflammatory cytokines. Conclusion: These results show that SDAPR could be an effective dietary supplement to relieve GM-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vitro and vivo.

show abstract

“…Recombinant murine CT‐1 was supplied by Peprotech (London, UK). CT‐1 doses were selected based on previous studies showing CT‐1 renoprotective effects …”

Section: Methodsmentioning

confidence: 99%

“…Some reports have shown that CT‐1 attenuates the expression of pro‐inflammatory cytokines such as IL‐1β, tumour necrosis factor alpha (TNF‐α), adhesion molecules intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule 1(VCAM‐1), inducible nitric oxide synthase (iNOs) and CD68 in several models of tissue damage, including endotoxemia, orthotropic liver transplant and renal ischaemia/reperfusion injury via nuclear factor (NF)‐κB inhibition . Also in rats, CT‐1 administration prevents contrast nephropathy and gentamicin nephrotoxicity . There are no data yet about the effect of endogenous CT‐1 in the development of tubulointerstitial fibrosis and renal damage.…”

Section: Introductionmentioning

confidence: 99%

Cardiotrophin‐1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease

et al. 2019

View full text Add to dashboard Cite

Aim Chronic kidney disease is characterized by tubulointerstitial fibrosis involving inflammation, tubular apoptosis, fibroblast proliferation and extracellular matrix accumulation. Cardiotrophin‐1, a member of the interleukin‐6 family of cytokines, protects several organs from damage by promoting survival and anti‐inflammatory effects. However, whether cardiotrophin‐1 participates in the response to chronic kidney injury leading to renal fibrosis is unknown. Methods We hypothesized and assessed the potential role of cardiotrophin‐1 in a mice model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). Results Three days after UUO, obstructed kidneys from cardiotrophin‐1−/− mice show higher expression of inflammatory markers IL‐1β, Cd68, ICAM‐1, COX‐2 and iNOs, higher activation of NF‐κB, higher amount of myofibroblasts and higher severity of tubular damage and apoptosis, compared with obstructed kidneys from wild‐type littermates. In a later stage, obstructed kidneys from cardiotrophin‐1−/− mice show higher fibrosis than obstructed kidneys from wild‐type mice. Interestingly, administration of exogenous cardiotrophin‐1 prevents the increased fibrosis resulting from the genetic knockout of cardiotrophin‐1 upon UUO, and supplementation of wild‐type mice with exogenous cardiotrophin‐1 further reduces the renal fibrosis induced by UUO. In vitro, renal myofibroblasts from cardiotrophin‐1−/− mice have higher collagen I and fibronectin expression and higher NF‐κB activation than wild‐type cells. Conclusions Cardiotrophin‐1 participates in the endogenous response that opposes renal damage by counteracting the inflammatory, apoptotic and fibrotic processes. And exogenous cardiotrophin‐1 is proposed as a candidate for the treatment and prevention of chronic renal fibrosis.

show abstract

Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats

Cited by 24 publications

References 58 publications

Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice

Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice

The Protective Effect of Sika Deer Antler Protein on Gentamicin-Induced Nephrotoxicity in Vitro and in Vivo

Cardiotrophin‐1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease

Contact Info

Product

Resources

About