3-nitrotyrosine and Kidney-Calculi

The objective of this study is to evaluate the safety and tolerability of inosine in patients with relapsing-remitting multiple sclerosis (RRMS). The secondary objectives are to assess the effects of inosine administration on serum urate (UA) levels, the progression of neurologic disability, the cumulative number of new, active lesions on magnetic resonance imaging (MRI), and changes in serum levels for markers of inflammation.. Oral administration of inosine was used to raise serum levels of the natural peroxynitrite scavenger UA in 16 patients with RRMS during a 1-year randomized, double-blind trial.. The endpoints studied were relapse rate, disability assessed by the Kurtzke Expanded Disability Status Scale (EDSS), MRI, and analysis of serum levels of nitrotyrosine, and oxidative and pro-inflammatory makers.. Increased serum UA levels correlated with a significant decrease in the number of gadolinium-enhanced lesions and improved EDSS. A number of MRI intensity-based parameters were altered by inosine treatment, in certain cases correlating with changes in serum UA levels. In a patient with low serum UA and high lesion activity, raising UA levels by inosine treatment decreased serum nitrotyrosine while increasing the ratio of Th2 to Th1 cytokines in circulating cells. The only side-effect correlated with inosine treatment was kidney stone formation in 4/16 subjects.. These data suggest that the use of inosine to raise serum UA levels may have benefits for at least some MS patients. The effect of this treatment is likely to be a consequence of inactivation of peroxynitrite-dependent free radicals. Close monitoring of serum UA levels as well as other measures are required to avoid the potential development of kidney stones.

Topics: Adjuvants, Immunologic; Administration, Oral; Adult; Brain; CD4 Lymphocyte Count; Central Nervous System; Cross-Over Studies; Cytokines; Disability Evaluation; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Inosine; Kidney Calculi; Magnetic Resonance Imaging; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Th1 Cells; Th2 Cells; Tyrosine; Uric Acid; Young Adult

Diets that ameliorate the adverse effects of uric acid (UA) on renal damage deserve attention. The effects of casein or soya protein combined with palm or safflower-seed oil on various serum parameters and renal histology were investigated on hyperuricaemic rats. Male Wistar rats administered with oxonic acid and UA to induce hyperuricaemia were fed with casein or soya protein plus palm- or safflower-seed oil-supplemented diets. Normal rats and hyperuricaemic rats with or without allopurinol treatment (150 mg/l in drinking water) were fed with casein plus maize oil-supplemented diets. After 8 weeks, allopurinol treatment and soya protein plus safflower-seed oil-supplemented diet significantly decreased serum UA in hyperuricaemic rats (one-way ANOVA; P < 0.05). In addition, soya protein and casein attenuated hyperuricaemia-induced decreases in serum albumin and insulin, respectively (two-way ANOVA; P < 0.05). Safflower-seed oil significantly decreased serum TAG and UA, whereas palm oil significantly increased serum cholesterol, TAG, blood urea N and creatinine. However, soya protein significantly decreased renal NO and nitrotyrosine and palm oil significantly decreased renal nitrotyrosine, TNF-alpha and interferon-gamma and increased renal transforming growth factor-beta. Casein with safflower-seed oil significantly attenuated renal tubulointerstitial nephritis, crystals and fibrosis. Comparing casein v. soya protein combined with palm or safflower-seed oil, the results support that casein with safflower-seed oil may be effective in attenuating hyperuricaemia-associated renal damage, while soya protein with safflower-seed oil may be beneficial in lowering serum UA and TAG.

Topics: Albumins; Analysis of Variance; Animals; Blood Urea Nitrogen; Caseins; Cholesterol; Creatinine; Diet; Dietary Fats; Dietary Proteins; Dietary Supplements; Drug Therapy, Combination; Fibrosis; Glycine max; Hyperuricemia; Insulin; Interferon-gamma; Kidney; Kidney Calculi; Male; Nephritis, Interstitial; Nitric Oxide; Oxonic Acid; Palm Oil; Plant Oils; Rats; Rats, Wistar; Safflower Oil; Soybean Proteins; Transforming Growth Factor beta; Triglycerides; Tumor Necrosis Factor-alpha; Tyrosine; Uric Acid