3-nitrotyrosine and Nephritis--Interstitial

The effects of cigarette smoke (CS) on cyclosporine (CsA)-induced nephrotoxicity are poorly studied. This study aims to assess the effects of previous exposure to CS on CsA nephrotoxicity.. Rats were either exposed to CS or sham (S) procedures for 10 min twice a day for 20 weeks. From the 16th to the 20th week, they received a low-salt diet. Beginning with the 17th week, they were given 2.5 mg/day CsA or vehicle (VH) for 3 weeks. The final groups were VH/CS, CsA/CS, VH/S, and CsA/S. On day 141, glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistance (RVR), tubulointerstitial fibrosis, and CsA blood levels were measured and immunohistochemistry was analyzed for renal α-smooth muscle actin (SMA), nitrotyrosine, and vimentin.. CsA decrease in GFR was enhanced by CS exposure. CsA associated with CS induced higher periglomerular α-SMA and renal nitrotyrosine expression. CsA decreased RBF, but increased RVR, tubulointerstitial fibrosis, and α-SMA and renal vimentin expression. These changes and the CsA blood levels were not affected by CS exposure.. CS aggravated the CsA-induced impairment of GFR and CS associated with CsA caused the development of periglomerular structural lesions and oxidative stress in a rat model of CsA nephrotoxicity.

Topics: Actins; Animals; Cyclosporine; Disease Models, Animal; Drug Synergism; Fibrosis; Glomerular Filtration Rate; Hematocrit; Hemodynamics; Humans; Immunosuppressive Agents; Kidney; Male; Nephritis, Interstitial; Rats; Rats, Wistar; Smoking; Tyrosine; Vimentin

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