Open Access : IJBNHY : 2278-778X Original Research Article International Journal of Bioassays *Corresponding Author: Dr. Ramesh Kumar, Ph.D. Associate Professor, Department of Biochemistry, Bundelkhand University, Jhansi, Uttar Pradesh, India. E-mail: ramesh_1995in@yahoo.co.in http://dx.doi.org/10.21746/ijbio.2016.11.001 pg. 4993 Serum nitric oxide levels in subjects with high creatinine value in comparison of healthy control subjects Ramesh Kumar*, Ritika Jain Department of Biochemistry, Bundelkhand University, Jhansi, Uttar Pradesh, India. Received: August 22, 2016; Revised: September 11, 2016; Accepted: September 18, 2016 Available online: 1 st November 2016 Abstract: Creatinine is a chemical waste molecule that is generated from muscle metabolism and is produced from creatine. The kidneys maintain blood creatinine levels in normal range. Creatinine has been found to be a fairly reliable indicator of kidney function. Elevated creatinine level signifies impaired kidney function or kidney disease. Since nitric oxide (NO) is produced by three types of Nitric Oxide Synthases (NOSs), rapid changes in stable oxidized metabolites (nitrite and nitrate) in the tissues and blood should be represented by the amount of stable forms in the serum and may reflect changes in the body. The serum samples were collected from the individuals with high levels of creatinine and normal range. Nitrite was measured by a Griess reaction while nitrate was measured using the enzymatic one step assay with nitrate reductase. The total 36 samples (18 normal range (N) and 18 high creatinine values (H)) were evaluated for the NO levels. The age group varies from 6-74 and 20-80 for normal and high level of creatinine respectively. The levels of creatinine in the normal range and high values varies from 0.71-0.93 (mean=0.86+0.01) and 1.59-11.59 (mean=4.34+0.77), respectively. When the nitrite (15.19+1.73 µM versus 12.84+1.19 µM, P>0.05) and nitrate (24.94+2.60 µM versus 27.76+2.42 µM, P>0.05) levels were compared between these groups no significant differences were observed. Results of this study reveal that there is no correlation between nitric oxide production and the serum creatinine levels. However, those results are preliminary and have to be confirmed in sample of larger size. Key words: Nitric oxide; iNOS; Creatinine; Kidney function Introduction Nitric oxide (NO) is heat-labile, unstable compound and is one of the few gaseous signaling molecules known (1). It is involved in many physiological and pathological processes within the body, both beneficial and detrimental (2,3). Appropriate levels of NO production are important in protecting organs from ischemic damage (4), whereas chronic expression of NO is associated with various malignancies and inflammatory conditions including juvenile diabetes, multiple sclerosis, arthritis and ulcerative colitis (5,6). Genetic factors including endothelial nitric oxide synthase (eNOS) were implicated in pathogenesis of rheumatoid arthritis, and extra- articular manifestations of rheumatoid arthritis were significantly greater among the carriers (7). Since NO is involved in various pathological states and is produced by three types of Nitric Oxide Synthases (NOSs), rapid changes in stable oxidized metabolites (nitrite and nitrate) in the tissues and blood should be represented by the amount of stable forms in serum and may reflect vascular activities and circulatory or inflammatory changes in the body (8). NO is produced in all tissues and organs by constitutive NOS (cNOS), which includes endothelial NOS (eNOS; isoform III) and neuronal NOS (nNOS; isoform I) and inducible NOS (iNOS; isoform II) (9). Therefore, pathophysiological changes such as atherosclerosis with coronary artery diseases (10, 11), endothelial dysfunction (12), pro-inflammation and inflammation seen in various diseases (13-16) may be to some extent studied by measuring NO metabolites in the peripheral blood (17- 20). Recent evidence suggests that NO deficiency is both a cause and consequence of chronic kidney disease (CKD) (21). Clinical data show decreased total NO production in patients with CKD and end-stage renal disease (ESRD) (22-26). In animal models of CKD, renal NO deficiency is evident irrespective of the initial insult (27–33) and enhanced progression is seen with superimposed NO synthase (NOS) inhibition and protection with L-arginine supplementation (34, 35). Furthermore, chronic NOS inhibition alone leads to hypertension, proteinuria, and renal injury (36). Within the kidney, loss of the neuronal isoform of NOS always associates with injury in multiple models of CKD (28-31, 33, 37) and correlates with level of damage and declining renal function (38).