Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway

Sharma, Isha; Liao, Yingjun; Zheng, Xiaoping; Kanwar, Yashpal S.

doi:10.1172/jci.insight.155487

Cited by 18 publications

(9 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings have been confirmed by histological examination, which revealed marked inflammatory cells infiltration in the parotid gland tissue of the GNT group. Sharma et al, 29 also demonstrated the ability of GNT to increase inflammatory mediators. Previous studies, in agreement with our data, reported the correlation of the inflammatory response to GNT in clinical and animal studies 30,31 .…”

Section: Discussionmentioning

confidence: 99%

Diacerein modulates TLR4/ NF‐κB/IL‐1β and TRPC1/CHOP signalling pathways in gentamicin‐induced parotid toxicity in rats

Ali

Mahmoud

Rifaai

et al. 2023

J Cellular Molecular Medi

View full text Add to dashboard Cite

The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days. Parotid oxidative stress parameters, besides inflammatory and apoptotic biomarkers, were evaluated. Salivary flow rate, transient receptor potential canonical 1 (TRCP1), and C/EBP homologous protein (CHOP) in parotid tissue were measured. A parotid histopathological examination and an interleukin-1 beta (IL-1β) immunohistochemical study were also performed. GNT significantly increased parotid oxidative stress, inflammatory, apoptotic and CHOP biomarkers with decreased salivary flow rate and TRCP1 level. A histopathological picture of parotid damage and high IL-1β immunoexpression were detected. DIA significantly normalized the distributed oxidative, inflammatory and apoptotic indicators, CHOP and TRCP1, with a prompt improvement in the histopathological picture and a decrease in IL-1β immunoexpression. These results reported that DIA protects against GNT-induced parotid toxicity via modulation of TLR4/NF-κB/IL-1β and TRPC1/CHOP signalling pathways. How to cite this article: Ali DM, Mahmoud MH, Rifaai RA, et al. Diacerein modulates TLR4/ NF-κB/IL-1β and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats.

show abstract

Section: Discussionmentioning

confidence: 99%

Diacerein modulates TLR4/ NF‐κB/IL‐1β and TRPC1/CHOP signalling pathways in gentamicin‐induced parotid toxicity in rats

Ali

Mahmoud

Rifaai

et al. 2023

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…MIOX promoter contains several response elements: oxidant-, antioxidant-, osmotic-, carbohydrate-, sterol-, response elements (18). While the role of MIOX has been linked to acute kidney injury, tubulointerstitial renal fibrosis, diabetic-associated nephropathies, and reactive oxygen species (ROS) generation (figure 3A), its role in ADPKD has not yet been reported (13,19,20) (19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

A Whole Exome Sequencing Study of a small Indian Autosomal Dominant Polycystic Kidney Disease Patient Cohort

Devi

Singh

Mohapatra

et al. 2023

Preprint

View full text Add to dashboard Cite

Polycystic Kidney Disease (PKD), which affects 1 in 500 to 1000 people globally, is a monogenic, hereditary nephropathy marked by the gradual growth and expansion of many fluid-filled kidney cysts often resulting in end-stage renal disease. Even within the same family, ADPKD shows variation in phenotype, genotype, and disease severity. While PKD1 and PKD2 mutations account for the majority of ADPKD cases (75% and 15%, respectively), about 7% of cases are currently genetically unexplained. The ADPKD-associated genes GANAB, DNAJB11, and ALG9 are also found in several genetically unresolved cases. Being a large gene constituted with 46 exons covering a 52 kb area and a 14 kb transcript and with six pseudogenes, PKD1 poses a challenge for direct PCR and Sanger sequencing of all exons and exon intron boundaries for mutation analysis. In order to find the disease-causing mutation(s) in a trio, whole exome sequencing (WES) was carried out. In the affected mother and daughter, no pathogenic variation(s) in the PKD1, PKD2, DNAJB11, GANAB, and ALG9 candidate genes was observed. However, WES analysis identified a frameshift deletion [c.32del/p.Leu11ArgfsTer61] in MIOX as the most likely cause of the disease shared by both affected individuals. This has not previously been reported in ADPKD. Further, the differential gene expression profile analysis of the data of cysts from GEO database showed reduced expression of MIOX in cystic samples of ADPKD individuals as compared to minimal cystic tissues (MCT) and control tissue samples. Myo-Inositol Oxygenase, or MIOX, is an enzyme that specifically expresses in renal tubules and catalyses the initial step of the kidney-based myoinositol catabolism pathway. Both affected candidates also shared benign variants and other variations of uncertain significance which might function as modifiers in the development of the disease. Further functional analysis of the variation(s) will clarify whether and how MIOX contributes to the development of the disease.

show abstract

“…Tominaga et al 22 showed that MIOX-induced oxidative stress linked to tunicamycin-induced endoplasmic reticulum stress may step-up the tubulointerstitial injury. Sharma et al 23 showed that gentamycin induced cellular injury in the AKI is further exacerbated by the overexpression of MIOX. Further, MIOX-mediated redox injury and necroptosis are involved in the pathogenesis of cadmium-induced renal injury 24 .…”

Section: Discussionmentioning

confidence: 99%

Serum myo-inositol oxygenase levels at hospital discharge predict progression to chronic kidney disease in community-acquired acute kidney injury

Kakkanattu

Kaur

Nagesh

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Acute kidney injury (AKI) increases the risk of morbidity, mortality, and progression to chronic kidney disease (CKD). There are few data on the risk of CKD following community-acquired AKI (CA-AKI) and its predictors from developing countries. We evaluated the association of a panel of serum and urine biomarkers at the time of hospital discharge with 4-month renal outcome in CA-AKI. Patients of either sex, aged between 18 and 70 years, with no underlying CKD, and with CA-AKI were recruited at the time of discharge from hospital in this prospective observational study. Levels of serum and urine biomarkers were analyzed and association between these markers and development of CKD, defined as eGFR < 60 ml/min/1.73 m2 or dialysis dependence at 4 month after discharge, were analyzed using multivariate logistic regression analysis and penalized least absolute shrinkage and selection operator logistic regression. Out of a total 126 patients followed up for 4 months, 25 developed CKD. Those who developed CKD were older (p = 0.008), had higher serum creatinine (p < 0.001) and lower serum albumin (p = 0.001) at discharge. Adjusted logistic regression showed that each 10% increase in standardized serum myo-inositol oxygenase (MIOX) level increased the odds of progression to CKD by 13.5%. With 10% increase in standardized urine Neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine and urine protein creatinine ratio (uPCR), increase in the odds of progression to CKD was 10.5%, 9.6% and 8%, respectively. Multivariable logistic model including serum MIOX, discharge serum creatinine and discharge uPCR, was able to predict the progression of CKD [AUC ROC 0.88; (95% CI 0.81, 0.95)]. High level serum MIOX levels at the time of discharge from hospital are associated with progression to CKD in patients with CA-AKI.

show abstract

Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway

Cited by 18 publications

References 57 publications

Diacerein modulates TLR4/ NF‐κB/IL‐1β and TRPC1/CHOP signalling pathways in gentamicin‐induced parotid toxicity in rats

Diacerein modulates TLR4/ NF‐κB/IL‐1β and TRPC1/CHOP signalling pathways in gentamicin‐induced parotid toxicity in rats

A Whole Exome Sequencing Study of a small Indian Autosomal Dominant Polycystic Kidney Disease Patient Cohort

Serum myo-inositol oxygenase levels at hospital discharge predict progression to chronic kidney disease in community-acquired acute kidney injury

Contact Info

Product

Resources

About