Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure

Fotheringham, Amelia K.; Solon-Biet, Samantha M.; Bielefeldt‐Ohmann, Helle; McCarthy, Domenica A.; McMahon, Aisling C.; Ruohonen, Kari; Li, Isaac T. S.; Sullivan, Mitchell A.; Whiddett, Rani; Borg, Danielle J.; Cogger, Victoria C.; Ballard, J. William O.; Turner, Nigel; Melvin, Richard G; Raubenheimer, David; Couteur, David G. Le; Simpson, Stephen J.; Forbes, Josephine M.

doi:10.1016/j.isci.2021.103308

Cited by 7 publications

(7 citation statements)

References 125 publications

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“…Dietary protein had the greatest influence on kidney function, where chronic low protein intake decreased glomerular filtration rates and kidney mass, whereas it increased kidney immune infiltration and structural injury [19].…”

Section: Resultsmentioning

confidence: 99%

The NADH-ubiquinone reductase and succinate dehydrogenase activity in the rat kidney mitochondria under the conditions of different protein and sucrose content in the diet

Voloshchuk¹,

Ursatyy²,

Kopylchuk³

2022

Ukr. Biochem. J.

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NaDh-ubiquinone reductase (Ec 7.1.1.2) and succinate dehydrogenase (Ec 1.3.5.1) activity, the levels of total ubiquinone and its redox forms, and the degree of oxidative modification of mitochondrial proteins in the rat kidney were investigated. It was found that when consuming a low-protein diet there is a decrease in NaDh-ubiquinone reductase and succinate dehydrogenase activity by 1.4-1.7 times, a 20% decrease in total ubiquinone and a quantitative redistribution of its oxidized and reduced form with a predominance of oxidized form. Under the studied conditions, there is no accumulation of carbonyl derivatives, but the level of free Sh-groups is significantly reduced compared with control. at the same time, in animals consuming a high-sucrose diet there is an increase in NaDh-ubiquinone reductase and succinate dehydrogenase activity by 1.5-2 times and maintenance of the total ubiquinone at the control level against the background of redistribution of its redox forms, namely a decrease in reduced ubiquinone and an increase in oxidized ubiquinone on average by 1.5 times. In addition, there is an intensification of the reactions of free radical damage of mitochondrial proteins in kidney cells, as evidenced by an increase in the level of carbonyl derivatives and a significant decrease in the level of free protein Sh-groups by approximately 1.4-1.5 times. the most pronounced changes in the studied indicators are found in animals that consumed a low-protein/ high-sucrose diet. In particular, an excessive consumption of sucrose on the background of protein deficiency is accompanied by a reduction of NaDh-ubiquinone reductase and succinate dehydrogenase activity by 1.7-2 times, a decrease in total ubiquinone level by approximately 1.4 times, and a two-fold decrease in reduced ubiquinone against the background of intensification of the free radical oxidation of mitochondrial proteins, which can be considered as a prerequisite for the impairment of the renal function under the conditions of carbohydrate-protein imbalance. K e y w o r d s: nutrients, kidney, NaDh-Ubiquinone reductase, succinate dehydrogenase, ubiquinone, carbonyl derivatives, protein Sh-group.

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Section: Resultsmentioning

confidence: 99%

The NADH-ubiquinone reductase and succinate dehydrogenase activity in the rat kidney mitochondria under the conditions of different protein and sucrose content in the diet

Voloshchuk¹,

Ursatyy²,

Kopylchuk³

2022

Ukr. Biochem. J.

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“…Thus, the cross‐talk between rostafuroxin‐sensitive signaling pathways and RAAS deserves further studies. Moreover, the possibility of cortical lesions that aggravate hypertension in chronic needs to be considered because low‐protein intake decreases the glomerular filtration rate and leads to more significant tubular injury and inflammation (Fotheringham et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na⁺ handling

Pereira‐Acácio,

Veloso‐Santos,

Alves‐Bezerra

et al. 2023

Physiological Reports

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Hypertension is a pandemic nowadays. We aimed to investigate whether chronic undernutrition modifies the response to the antihypertensive drug rostafuroxin in juvenile hypertensive rats. Chronic undernutrition was induced in male rats using a multideficient diet known as the Regional Basic Diet (RBD), mimicking alimentary habits in impoverished regions worldwide. Animals were given RBD—or a control/CTRL normal diet for rodents—from weaning to 90 days, and rostafuroxin (1 mg/kg body mass) was orally administered from day 60 onwards. For the last 2 days, the rats were hosted in metabolic cages to measure food/energy, water, Na+ ingestion, and urinary volume. Rostafuroxin increased food/energy/Na+ intake in CTRL and RBD rats but had opposite effects on Na+ balance (intake minus urinary excretion). The drug normalized the decreased plasma Na+ concentration in RBD rats, increased urinary volume in RBD but not in CTRL, and decreased and increased urinary Na+ concentration in the RBD and CTRL groups, respectively. Rostafuroxin decreased the ouabain‐sensitive (Na++K+)ATPase and increased the ouabain‐resistant Na+‐ATPase from proximal tubule cells in both groups and normalized the systolic blood pressure in RBD without effect in CTRL rats. We conclude that chronic undernutrition modifies the response of blood pressure and metabolic responses to rostafuroxin.

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“…Питання порушень метаболічних процесів за умов надлишку сахарози або дефіциту протеїну в харчовому раціоні заслуговує на особливу увагу [1,2]. Показано, що хронічне споживання низькопротеїнового раціону може призводити до зниження маси нирок, зміни фільтраційної здатності клубочків, запалення ниркових канальців [3]. Так само надлишкове споживання сахарози сприяє прогресуванню хронічної ниркової недостатності, в основі виникнення якої лежить порушення окисновідновного балансу та внутрішньониркове запалення [4].…”

Section: вступunclassified

Activity of Poliolytic Pathway Enzymes in Rat Kidneys Under Conditions of Different Protein and Sucrose Supply in the Diet

Voloshchuk,

Kopylchuk

2024

Fiziol Zh

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The study examined the activity of enzymes in the polyol pathway and the status of free radical processes in the kidneys of rats subjected to different dietary protein and sucrose levels. It was found that the kidneys of animals consuming a highsucrose diet, irrespective of protein content, exhibited the highest increase in the activity of polyol pathway enzymes, namely aldose reductase and sorbitol dehydrogenase. Consumption of a high-sucrose diet enhances the generation of O2 •- in the kidneys by almost twofold, and hydroxyl radical by over fourfold compared to control indicators. This is accompanied by a twofold increase in the content of TBARS-active products and a threefold increase in the content of carbonyl derivatives of proteins, against the background of a decrease in the content of free thiol groups in proteins. The pronounced generation of hydroxyl radicals, accumulation of TBARS-active products, and reduction in the content of free SH-groups in proteins are characteristic of animals that consumed a high-sucrose diet in the context of dietary protein deficiency. It has been demonstrated that excessive sucrose consumption is a critical factor, influencing the activity of enzymes in the polyol pathway and the intensity of free radical processes. The obtained results may be considered as predisposing factors for disruptions in the structural and functional organization of the kidneys under conditions of nutrient imbalance.

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Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure

Cited by 7 publications

References 125 publications

The NADH-ubiquinone reductase and succinate dehydrogenase activity in the rat kidney mitochondria under the conditions of different protein and sucrose content in the diet

The NADH-ubiquinone reductase and succinate dehydrogenase activity in the rat kidney mitochondria under the conditions of different protein and sucrose content in the diet

Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na⁺ handling

Activity of Poliolytic Pathway Enzymes in Rat Kidneys Under Conditions of Different Protein and Sucrose Supply in the Diet

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Kidney disease risk factors do not explain impacts of low dietary protein on kidney function and structure

Cited by 7 publications

References 125 publications

The NADH-ubiquinone reductase and succinate dehydrogenase activity in the rat kidney mitochondria under the conditions of different protein and sucrose content in the diet

The NADH-ubiquinone reductase and succinate dehydrogenase activity in the rat kidney mitochondria under the conditions of different protein and sucrose content in the diet

Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na+ handling

Activity of Poliolytic Pathway Enzymes in Rat Kidneys Under Conditions of Different Protein and Sucrose Supply in the Diet

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Different antihypertensive and metabolic responses to rostafuroxin in undernourished and normonourished male rats: Outcomes on bodily Na⁺ handling