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High Sodium-Induced Oxidative Stress and Poor Anticrystallization Defense Aggravate Calcium Oxalate Crystal Formation in Rat Hyperoxaluric Kidneys.

Huang HS, Ma MC - PLoS ONE (2015)

Bottom Line: Enhanced sodium excretion is associated with intrarenal oxidative stress.Compared to normal sodium, HS slightly increased calcium excretion despite diuresis; however, the result did not reach statistical significance.Increased urinary malondialdehyde excretion, in situ superoxide production, NAD(P)H oxidase and xanthine oxidase expression and activity, and decreased antioxidant enzyme expression or activity in the HS+HP kidney indicated exaggerated oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, National Cheng Kung University Hospital, Tainan, Taiwan.

ABSTRACT
Enhanced sodium excretion is associated with intrarenal oxidative stress. The present study evaluated whether oxidative stress caused by high sodium (HS) may be involved in calcium oxalate crystal formation. Male rats were fed a sodium-depleted diet. Normal-sodium and HS diets were achieved by providing drinking water containing 0.3% and 3% NaCl, respectively. Rats were fed a sodium-depleted diet with 5% hydroxyl-L-proline (HP) for 7 and 42 days to induce hyperoxaluria and/or calcium oxalate deposition. Compared to normal sodium, HS slightly increased calcium excretion despite diuresis; however, the result did not reach statistical significance. HS did not affect the hyperoxaluria, hypocalciuria or supersaturation caused by HP; however, it increased calcium oxalate crystal deposition soon after 7 days of co-treatment. Massive calcium oxalate formation and calcium crystal excretion in HS+HP rats were seen after 42 days of treatment. HP-mediated hypocitraturia was further exacerbated by HS. Moreover, HS aggravated HP-induced renal injury and tubular damage via increased apoptosis and oxidative stress. Increased urinary malondialdehyde excretion, in situ superoxide production, NAD(P)H oxidase and xanthine oxidase expression and activity, and decreased antioxidant enzyme expression or activity in the HS+HP kidney indicated exaggerated oxidative stress. Interestingly, this redox imbalance was associated with reduced renal osteopontin and Tamm-Horsfall protein expression (via increased excretion) and sodium-dependent dicarboxylate cotransporter NaDC-1 upregulation. Collectively, our results demonstrate that a HS diet induces massive crystal formation in the hyperoxaluric kidney; this is not due to increased urinary calcium excretion but is related to oxidative injury and loss of anticrystallization defense.

No MeSH data available.


Related in: MedlinePlus

Renal damage makers and lipid peroxidation after high sodium or hyperoxaluric treatment.(A) Urinary levels of the tubular enzyme N-acetyl-β-glucosaminidase (NAG) were used as a marker of tubular damage at days 7 and 42. (B and C) Renal injury was evaluated according to renal expression of cytochrome c (Cyto c) and poly (ADP-ribose) polymerase (PARP), which promote apoptosis after tissue injury. Representative blots from three rats show expression of cytochrome c and full-length and cleaved PARP (40 μg of cytosolic protein per lane). The lower bar graph shows the ratio of cytochrome c to actin, and the ratio of full-length to cleaved PARP as a measure of PARP activity. DU, band density unit. (D) Urinary levels of malondialdehyde (MDA) were measured to evaluate intrarenal oxidative stress after 7 and 42 days of HS or HP treatment. N = 6 in each group and time-point. NS, normal sodium; HP, hydroxyl-L-proline; HS, high sodium. *p<0.05, HP or HS vs. NS group; #p<0.05, HS+HP vs. HP group; +p<0.05, HS+HP vs. HS group.
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pone.0134764.g004: Renal damage makers and lipid peroxidation after high sodium or hyperoxaluric treatment.(A) Urinary levels of the tubular enzyme N-acetyl-β-glucosaminidase (NAG) were used as a marker of tubular damage at days 7 and 42. (B and C) Renal injury was evaluated according to renal expression of cytochrome c (Cyto c) and poly (ADP-ribose) polymerase (PARP), which promote apoptosis after tissue injury. Representative blots from three rats show expression of cytochrome c and full-length and cleaved PARP (40 μg of cytosolic protein per lane). The lower bar graph shows the ratio of cytochrome c to actin, and the ratio of full-length to cleaved PARP as a measure of PARP activity. DU, band density unit. (D) Urinary levels of malondialdehyde (MDA) were measured to evaluate intrarenal oxidative stress after 7 and 42 days of HS or HP treatment. N = 6 in each group and time-point. NS, normal sodium; HP, hydroxyl-L-proline; HS, high sodium. *p<0.05, HP or HS vs. NS group; #p<0.05, HS+HP vs. HP group; +p<0.05, HS+HP vs. HS group.

Mentions: Tubular damage aggregates CaOx crystals [12, 13]. Therefore, we next tested whether HS may affect tubular damage in the HP kidney. Using a sensitive marker of tubular damage, our results showed that urinary excretion of N-acetyl-β-glucosaminidase (NAG) in HP rats increased significantly in a time-dependent manner compared with that in NS rats (Fig 4A). HS itself had no effect on NAG excretion, but aggravated NAG excretion in HP rats.


High Sodium-Induced Oxidative Stress and Poor Anticrystallization Defense Aggravate Calcium Oxalate Crystal Formation in Rat Hyperoxaluric Kidneys.

Huang HS, Ma MC - PLoS ONE (2015)

Renal damage makers and lipid peroxidation after high sodium or hyperoxaluric treatment.(A) Urinary levels of the tubular enzyme N-acetyl-β-glucosaminidase (NAG) were used as a marker of tubular damage at days 7 and 42. (B and C) Renal injury was evaluated according to renal expression of cytochrome c (Cyto c) and poly (ADP-ribose) polymerase (PARP), which promote apoptosis after tissue injury. Representative blots from three rats show expression of cytochrome c and full-length and cleaved PARP (40 μg of cytosolic protein per lane). The lower bar graph shows the ratio of cytochrome c to actin, and the ratio of full-length to cleaved PARP as a measure of PARP activity. DU, band density unit. (D) Urinary levels of malondialdehyde (MDA) were measured to evaluate intrarenal oxidative stress after 7 and 42 days of HS or HP treatment. N = 6 in each group and time-point. NS, normal sodium; HP, hydroxyl-L-proline; HS, high sodium. *p<0.05, HP or HS vs. NS group; #p<0.05, HS+HP vs. HP group; +p<0.05, HS+HP vs. HS group.
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pone.0134764.g004: Renal damage makers and lipid peroxidation after high sodium or hyperoxaluric treatment.(A) Urinary levels of the tubular enzyme N-acetyl-β-glucosaminidase (NAG) were used as a marker of tubular damage at days 7 and 42. (B and C) Renal injury was evaluated according to renal expression of cytochrome c (Cyto c) and poly (ADP-ribose) polymerase (PARP), which promote apoptosis after tissue injury. Representative blots from three rats show expression of cytochrome c and full-length and cleaved PARP (40 μg of cytosolic protein per lane). The lower bar graph shows the ratio of cytochrome c to actin, and the ratio of full-length to cleaved PARP as a measure of PARP activity. DU, band density unit. (D) Urinary levels of malondialdehyde (MDA) were measured to evaluate intrarenal oxidative stress after 7 and 42 days of HS or HP treatment. N = 6 in each group and time-point. NS, normal sodium; HP, hydroxyl-L-proline; HS, high sodium. *p<0.05, HP or HS vs. NS group; #p<0.05, HS+HP vs. HP group; +p<0.05, HS+HP vs. HS group.
Mentions: Tubular damage aggregates CaOx crystals [12, 13]. Therefore, we next tested whether HS may affect tubular damage in the HP kidney. Using a sensitive marker of tubular damage, our results showed that urinary excretion of N-acetyl-β-glucosaminidase (NAG) in HP rats increased significantly in a time-dependent manner compared with that in NS rats (Fig 4A). HS itself had no effect on NAG excretion, but aggravated NAG excretion in HP rats.

Bottom Line: Enhanced sodium excretion is associated with intrarenal oxidative stress.Compared to normal sodium, HS slightly increased calcium excretion despite diuresis; however, the result did not reach statistical significance.Increased urinary malondialdehyde excretion, in situ superoxide production, NAD(P)H oxidase and xanthine oxidase expression and activity, and decreased antioxidant enzyme expression or activity in the HS+HP kidney indicated exaggerated oxidative stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, National Cheng Kung University Hospital, Tainan, Taiwan.

ABSTRACT
Enhanced sodium excretion is associated with intrarenal oxidative stress. The present study evaluated whether oxidative stress caused by high sodium (HS) may be involved in calcium oxalate crystal formation. Male rats were fed a sodium-depleted diet. Normal-sodium and HS diets were achieved by providing drinking water containing 0.3% and 3% NaCl, respectively. Rats were fed a sodium-depleted diet with 5% hydroxyl-L-proline (HP) for 7 and 42 days to induce hyperoxaluria and/or calcium oxalate deposition. Compared to normal sodium, HS slightly increased calcium excretion despite diuresis; however, the result did not reach statistical significance. HS did not affect the hyperoxaluria, hypocalciuria or supersaturation caused by HP; however, it increased calcium oxalate crystal deposition soon after 7 days of co-treatment. Massive calcium oxalate formation and calcium crystal excretion in HS+HP rats were seen after 42 days of treatment. HP-mediated hypocitraturia was further exacerbated by HS. Moreover, HS aggravated HP-induced renal injury and tubular damage via increased apoptosis and oxidative stress. Increased urinary malondialdehyde excretion, in situ superoxide production, NAD(P)H oxidase and xanthine oxidase expression and activity, and decreased antioxidant enzyme expression or activity in the HS+HP kidney indicated exaggerated oxidative stress. Interestingly, this redox imbalance was associated with reduced renal osteopontin and Tamm-Horsfall protein expression (via increased excretion) and sodium-dependent dicarboxylate cotransporter NaDC-1 upregulation. Collectively, our results demonstrate that a HS diet induces massive crystal formation in the hyperoxaluric kidney; this is not due to increased urinary calcium excretion but is related to oxidative injury and loss of anticrystallization defense.

No MeSH data available.


Related in: MedlinePlus