ABSTRACT
BACKGROUND: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. METHODS: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔΨm) measurement. RESULTS: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney ΔΨm. CONCLUSION: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
Subject(s)
Edaravone , Free Radical Scavengers , Reperfusion Injury , Animals , Apoptosis , Edaravone/pharmacology , Free Radical Scavengers/pharmacology , Janus Kinases/drug effects , Male , Mitochondria , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , STAT Transcription Factors/drug effects , Signal Transduction/drug effectsABSTRACT
BACKGROUND: Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism. METHODS: Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔψM) measurement. RESULTS: The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney (ΔψM). CONCLUSION: Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
Subject(s)
Animals , Male , Rats , Reperfusion Injury/drug therapy , Free Radical Scavengers/pharmacology , Edaravone/pharmacology , Signal Transduction/drug effects , Rats, Sprague-Dawley , Apoptosis , STAT Transcription Factors/drug effects , Janus Kinases/drug effects , MitochondriaABSTRACT
Breeding to increase beta-carotene levels in cereal grains, termed provitamin A biofortification, is an economical approach to address dietary vitamin A deficiency in the developing world. Experimental evidence from association and linkage populations in maize (Zea mays L.) demonstrate that the gene encoding beta-carotene hydroxylase 1 (crtRB1) underlies a principal quantitative trait locus associated with beta-carotene concentration and conversion in maize kernels. crtRB1 alleles associated with reduced transcript expression correlate with higher beta-carotene concentrations. Genetic variation at crtRB1 also affects hydroxylation efficiency among encoded allozymes, as observed by resultant carotenoid profiles in recombinant expression assays. The most favorable crtRB1 alleles, rare in frequency and unique to temperate germplasm, are being introgressed via inexpensive PCR marker-assisted selection into tropical maize germplasm adapted to developing countries, where it is most needed for human health.