The synthetic triterpenoid RTA dh404 (CDDO-dhTFEA) restores Nrf2 activity and attenuates oxidative stress, inflammation, and fibrosis in rats with chronic kidney disease

Figures & data

Table 1. General parameters.

	Control^a	CKD^a	CKD + RTA dh404^a
Body weight (g)	417 ± 4.2	391 ± 14*	397 ± 14.5*
Serum creatinine  (mg/dL)	0.455 ± 0.033	0.794 ± 0.059*	0.743 ± 0.035*
Urine protein  (mg/24 h)	10.2 ± 4.5	75.1 ± 13.4*	53.7 ± 4.8#
Urine volume  (mL/24 h)	11.0 ± 1.5	20.1 ± 2.0*	21.2 ± 3.0*
Hematocrit (%)	43 ± 1	39 ± 1*	43 ± 1#
Mean arterial  pressure (mmHg)	113 ± 5	146 ± 2*	119 ± 3#
Plasma MDA  (µmol/L)	0.7 ± 0.1	1.4 ± 0.1*	0.9 ± 0.1#

^aValues are presented as mean ± standard error of the mean (n = 5–7 in each group).

*p < 0.05 versus control.

#p < 0.05 versus CKD.

Figure 1. Representative western blots and group data depicting protein abundance of phospho-IκB and nuclear contents of p65 active subunit of NF-κB, iNOS and COX-2 in the renal tissues of sham-operated control (CTL; n = 6) and a 5/6 nephrectomized rat CKD treated with vehicle (CKD; n = 9) or RTA dh404 (CKD + RTA dh404; n = 9); *p < 0.05 versus CTL, #p < 0.05 versus CKD.

Figure 2. Representative western blots and group data depicting protein abundance of NAD(P)H oxidase subunits (p22^phox, gp91^phox and rac1) and NT in the renal tissues of sham-operated control (CTL; n = 6) and a 5/6 nephrectomized rat CKD treated with vehicle (CKD; n = 9) or RTA dh404 (CKD + RTA dh404; n = 9); *p < 0.05 versus CTL, **p < 0.01 versus CTL, #p < 0.05 versus CKD.

Figure 3. Representative western blots and group data depicting protein abundance of Nrf2, Keap1 and Nrf2 downstream gene products: catalase, HO-1 and catalytic (GCLC) and modulatory (GCLM) subunits of glutamate-cysteine ligase in the renal tissues of sham-operated control (CTL; n = 6) and a 5/6 nephrectomized rat CKD treated with vehicle (CKD; n = 9) or RTA dh404 (CKD + RTA dh404; n = 9); *p < 0.05 versus CTL, **p < 0.01 versus CTL, #p < 0.05 versus CKD.

Figure 4. Messenger RNA expression of peroxiredoxin 1 (Prdx1), thioredoxin 1 (Txn1) and thioredoxin reductase 1 (Txnrd1) in the renal tissues of sham-operated control (CTL; n = 6) and a 5/6 nephrectomized rat CKD treated with vehicle (CKD; n = 9) or RTA dh404 (CKD + RTA dh404; n = 9); **p < 0.01 versus CTL, #p < 0.05 versus CKD.

Figure 5. Representative western blots and group data depicting protein abundance of TGF-β, α-SMA, extracellular signal-regulated kinase 1/2 (ERK 1/2) and SMAD7 in the renal tissues of sham-operated control (CTL; n = 6) and a 5/6 nephrectomized rat CKD treated with vehicle (CKD; n = 9) or RTA dh404 (CKD + RTA dh404; n = 9); *p < 0.05 versus CTL, **p < 0.01 versus CTL, #p < 0.05 versus CKD, ##p < 0.01 versus CKD.

Figure 6. Representative photomicrographs of the H&E stained renal tissue (20X) in a sham-operated control (A) and a 5/6 nephrectomized rat (CKD)] treated with vehicle (B) or RTA dh404 (C). The remnant kidney in the CKD animals (B) exhibited significant glomerulosclerosis, tubulo-interstitial injury and heavy inflammatory cell infiltration. RTA dh404 treatment-reduced inflammatory cell infiltration and glomerular and tubulo-interstitial injury (C).

Figure 7. Representative photomicrographs of the PAS-stained renal tissue in a sham-operated control (A) and a 5/6 nephrectomized rat (CKD) treated with vehicle (B) or RTA dh404 (C). The remnant kidney in the CKD animals exhibited significant fibrosis (B) which was reduced with RTA dh404 treatment (C). 20 × magnification.