sodium-nitrite and Kidney-Diseases

Nitric oxide (NO) has numerous important functions in the kidney, and long-term blockage of nitric oxide synthases in rats by L-NAME results in severe hypertension and progressive kidney damage. On the other hand, NO production seems to be low in patients with chronic kidney disease (CKD), and NO deficiency may play a role in CKD progression. In this review, we summarized the mechanisms of amelioration of renal injury induced by L-NAME treated rats by treatment of nitrite. First, we demonstrate whether orally-administrated nitrite-derived NO can shift to the circulation. When 3mg/kg body weight Na(15)NO(2) was orally administered to rats, an apparent EPR signal derived from Hb(15)NO (A(z)=23.4 gauss) appeared in the blood, indicating that orally ingested nitrite can be a source of NO in vivo. Next, in order to clarify the capacity of nitrite to prevent renal disease, we administered low-dose nitrite (LDN: 0.1mg of sodium nitrite in 1L of drinking water), medium-dose nitrite (MDN: 1mg sodium nitrite/L, which corresponds to the amount of nitrite ingested by vegetarians), or high-dose nitrite (HDN: 10mg sodium nitrite/L) to rats simultaneously with L-NAME (1 g l-NAME/L) for 8 weeks, then examined the blood NO level as a hemoglobin-NO adduct (iron-nitrosyl-hemoglobin) using electron paramagnetic resonance spectroscopy, urinary protein excretion, and renal histological changes at the end of the experiment. It was found that oral administration of MDN and HDN but not LDN increased the blood iron-nitrosyl-hemoglobin concentration to the normal level, ameliorated the L-NAME-induced proteinuria, and reduced renal histological damage. The findings demonstrate that chronic administration of a mid-level dietary dose of nitrite restores the circulating iron-nitrosyl-hemoglobin levels reduced by L-NAME and that maintenance of the circulating iron-nitrosyl-hemoglobin level in a controlled range protects against L-NAME-induced renal injury. Taking these findings together, we propose that dietary supplementation of nitrite is a potentially useful nonpharmacological strategy for maintaining circulating NO level in order to prevent or slow the progression of renal disease. It had been believed that nitrite could result in intragastric formation of nitrosamines, which had been linked to esophageal and other gastrointestinal cancers. However, there is no positive association between the intake of nitrate or nitrite and gastric and pancreatic cancer by recent researches. Furth

Topics: Animals; Diet; Hypertension; Kidney Diseases; NG-Nitroarginine Methyl Ester; Rats; Sodium Nitrite

Sodium nitrite is a widely used color fixative and preservative. However, it has been reported to exert deleterious toxic effects on various body organs. Moreover, thymoquinone (TQ), the active constituent of Nigella sativa oil is known to possess beneficial antioxidant and anti-inflammatory effects. The present study was conducted to evaluate the potential protective effects of TQ against sodium nitrite-induced renal toxicity.. Male Sprague-Dawley rats were treated with sodium nitrite (80mg/kg, po, daily) in presence or absence of TQ (25 and 50mg/kg, po, daily). Morphological changes in renal sections were assessed by staining with Hematoxylin/Eosin and Periodic acid-Schiff. Renal homogenate was used for measurement of oxidative stress markers (MDA and GSH), inflammatory markers (CRP, TNF-α, IL-6, IL-1β), anti-inflammatory cytokines (IL-10 and IL-4) and apoptotic markers (caspase-3/caspase-8/caspase-9).. Treatment with sodium nitrite significantly increased markers of renal dysfunction, oxidative stress, inflammation and apoptosis. These effects were markedly attenuated by TQ in dose dependent manner.. TQ has a potential protective effect against sodium nitrite-induced renal toxicity. This can be attributed to its ability to dampen oxidative stress, restore the normal balance between pro- and anti-inflammatory cytokines and protect renal tissue form extrinsic and intrinsic apoptosis.

Topics: Animals; Apoptosis; Benzoquinones; Cytokines; Dose-Response Relationship, Drug; Food Preservatives; Inflammation; Inflammation Mediators; Kidney Diseases; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sodium Nitrite

In hypoxic and acidic tissue environments, nitrite is metabolised to nitric oxide, thus, bringing about novel therapeutic options in myocardial infarction, peripheral artery disease, stroke, and hypertension. Following renal ischemia, reperfusion of the kidney remains incomplete and tissue oxygenation is reduced for several minutes to hours. Thus, in renal ischemia-reperfusion injury, providing nitrite may have outstanding therapeutic value. Here we demonstrate nitrite's distinct potential to rapidly restore tissue oxygenation in the renal cortex and medulla after 45 minutes of complete unilateral kidney ischemia in the rat. Notably, tissue oxygenation was completely restored, while tissue perfusion did not fully reach pre-ischemia levels within 60 minutes of reperfusion. Nitrite was infused intravenously in a dose, which can be translated to the human. Specifically, methaemoglobin did not exceed 3%, which is biologically negligible. Hypotension was not observed. Providing nitrite well before ischemia and maintaining nitrite infusion throughout the reperfusion period prevented the increase in serum creatinine by ischemia reperfusion injury. In conclusion, low-dose nitrite restores renal tissue oxygenation in renal ischemia reperfusion injury and enhances regional kidney post-ischemic perfusion. As nitrite provides nitric oxide predominantly in hypoxic tissues, it may prove a specific measure to reduce renal ischemia reperfusion injury.

Topics: Administration, Intravenous; Animals; Drug Evaluation, Preclinical; Hemodynamics; Ischemia; Kidney; Kidney Diseases; Male; Protective Agents; Rats, Wistar; Reperfusion Injury; Sodium Nitrite

The diuretic drug hydrochlorothiazide was administered to 24 male and 24 female F344 rats as a mixture of 0.1% in powdered food. A parallel group of the same size was given 0.1% hydrochlorothiazide plus 0.2% sodium nitrite in the food. A third group received 0.2% sodium nitrite in the food and there was a similar group of untreated controls. The treatments were well tolerated and there was no significant life shortening. A majority of the rats given hydrochlorothiazide, with or without nitrite, developed chronic progressive nephropathy, which was more severe in males than in females. Associated with this were diffuse parathyroid hyperplasia in both groups receiving the drug, also more severe in males than in females, and parallel increases in lesions of the blood vessels (mural thrombosis of the heart and polyarteritis). The few adenomas of the parathyroid and tubular cell adenomas of the kidney in rats ingesting hydrochlorothiazide were not statistically significant.

Topics: Animals; Arteritis; Carcinogens; Female; Heart Diseases; Hydrochlorothiazide; Kidney Diseases; Male; Nitrites; Parathyroid Diseases; Rats; Rats, Inbred F344; Sodium Nitrite; Thrombosis