Curcumin prevents mitochondrial dynamics disturbances in early 5/6 nephrectomy: Relation to oxidative stress and mitochondrial bioenergetics

Abstract

Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts. In addition, it was found that 5/6NX shifted mitochondrial dynamics to fusion, which was evidenced by increased optic atrophy 1 and mitofusin 1 (Mfn1) and decreased fission 1 and dynamin-related protein 1 expressions. These data were confirmed by morphological analysis and immunoelectron microscopy of Mfn-1. All the above-described mechanisms were prevented by curcumin. Also, it was found that curcumin prevented renal dysfunction by improving renal blood flow and the total antioxidant capacity induced by 5/6NX. Moreover, in glomeruli and proximal tubules 5/6NX-induced superoxide anion production by uncoupled nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) dependent way, this latter was associated with increased phosphorylation of serine 304 of p47phox subunit of NOX. In conclusion, this study shows that curcumin pretreatment decreases early 5/6NX-induced altered mitochondrial dynamics, bioenergetics, and oxidative stress, which may be associated with the preservation of renal function. © 2016 BioFactors, 43(2):293-310, 2017.

Orientin Protects Podocytes from High Glucose Induced Apoptosis through Mitophagy

“…They are a class of highly shape‐changing organelles which continuously undergo fusion and fission. In physiological conditions, the shape of the mitochondria is normal, in the form of a rod or an ellipse, but their shape becomes swollen and ruptured to round under stress including various kidney diseases . The selective scavenging effect of autophagy on mitochondria is closely related to the biological activity of mitochondria .…”

An S-adenosyl Methionine Synthetase (SAMS) Gene from Andropogon virginicus L. Confers Aluminum Stress Tolerance and Facilitates Epigenetic Gene Regulation in Arabidopsis thaliana

“…Two of the constructed A. thaliana TF expressing the AvSAMS1 gene (TF3 and TF6) and their parental non-TF line, Col-0, were treated with various stressors and then measured for root length. Results were shown as relative root growth (%) as described previously (Ezaki et al, 2000). Error bars indicate SD.…”

“…For A. thaliana , seeds were submerged in distilled water for 4 days at 4°C, grown in soil for approximately 3 week and then used for all experiments except for stress sensitivity tests. For stress sensitivity tests, seeds of A. thaliana were sterilized, submerged in sterilized water for 4 days at 4°C and then grown in hydroponic conditions with a fine nylon mesh net and a floating support in 1/6 MS medium (adjusted to pH 5.7; Ezaki et al, 2000) for 12 to 15 days. All plants were grown under fluorescent illumination (approximately 50 μEm −2 s −1 , 16 h of light and 8 h of darkness) at 25°C.…”

“…Seedlings of A. thaliana grown in 1/6 MS medium (10-days to 2-weeks-old) were also exposed to 300 μM AlCl 3 in a fresh 1/6 MS medium (adjusted to pH 4.2) for 2 days or to 35 μM CdCl 2 , 50 μM CuSO 4 , 300 μM PbCl 3 , 200 μM ZnCl 2 , 1.5 mM DM or 1.5 mM H 2 O 2 in a fresh 1/6 MS medium (adjusted to pH 5.7) for 2 days. Root length was randomly measured for more than 20 plants in each condition to calculate the relative root growth which was shown previously (Ezaki et al, 2000). …”

Nutrients, Nutraceuticals and Xenobiotics Affecting Renal Health

“…As already reported for CKD animal model and human studies [95,96], curcumin exhibits antioxidant properties, potentially useful in a prevention setting. In this regard, in a very recent animal study curcumin has been shown to be able to prevent early damage induced by 5/6 nephrectomy, not only ameliorating total antioxidant capacity, but also improving renal blood flow and acting in terms of mitochondrial function and bioenergetics [100]. But probably the most interesting systemic action of curcumin occurs at the intestinal level.…”