Colchicine vs. omega-3 fatty acids for prevention of chronic cyclosporine nephrotoxicity in Sprague Dawley rats: an experimental animal model.

BACKGROUND: In view of the high cost of the new immunosuppressive drugs, which represents a challenge for both patients and governmental resources especially in developing countries, trials to prevent side effects of the first calcineurin inhibitor discovered (cyclosporine, Cs) are of particular interest. METHODS: In this prospective randomized experimental study, 60 male Sprague Dawley rats were enrolled. Group 1 served as negative control group and received olive oil. Group 2 received Cs orally 100 mg/kg for 80 days and served as positive control group. Group 3 was given daily colchicine (30 microg/kg/day) in addition to Cs. Group 4 was given omega-3 fatty acids (100 mg/kg/day) in addition to Cs. Animals were subjected every other week to laboratory assessment for serum creatinine, sodium, potassium, and Cs whole-blood through levels. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. RESULTS: There were no significant differences in serum creatinine, creatinine clearance, and serum sodium and potassium in all groups. Histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner strip of the outer medulla in all Cs-treated animals. Morphological changes were significantly less in colchicine-treated rats compared to omega-3 fatty acid-treated rats and absent in the negative control group. Furthermore, immunostaining showed positive reactions for vimentin in Cs-treated animals only. CONCLUSIONS: Colchicine and omega-3 fatty acids are protective for the kidney against cyclosporine-induced nephropathy; however, colchicine is more protective than omega-3 fatty acid.

Correlation between levels of TNF-alpha and IL-6 and hematological involvement in SLE Egyptian patients with lupus nephritis.

BACKGROUND: Systemic lupus Erythematosus (SLE) is a rheumatic autoimmune disease characterized by multisystem organ involvement and by high titers of auto antibodies against several nuclear and cytoplasmic antigens. Numerous abnormalities of the cytokine network have been described in patients suffering from SLE. However the role of cytokines in different organ involvement is not yet well defined. OBJECTIVE: To determine if levels of Interlukin-6 (IL-6) and Tumor necrosis factor (TNF-alpha) correlate with SLE disease activity in Egyptian SLE patients and more specifically with hematological involvement. METHODS: Levels of TNF-alpha and IL-6 in serum samples from sixty individuals (40 with Systemic lupus Erythmatosus and 20 healthy controls) were determined and renal biopsies were obtained from SLE patients. RESULTS: Levels of TNF-alpha and IL-6 were higher in SLE patients with active compared with inactive hematological disease. Further analysis showed that this association was dependent on inverse correlation (P=0.017, r=-0.49) for IL-6 and (P=0.76, r=-.243) for TNF-alpha. The mean level of TNF-alpha and Il-6 was (766.95+/-357.82 pg/ml) and (135.4+/-54.23 pg/ml) respectively for patients with active disease while it was (314.01+/-100.87 pg/ml) and (47.33+/-18.61 pg/ml) for those with inactive disease and (172.7+/-39.19 pg/ml) and (21.15+/-10.99 pg/ml) for the healthy control group respectively. The difference was statistically significant (P=0.002). We found significant positive correlations between TNF-alpha and IL-6 and the SLE Disease Activity Index (SLEDAI) score. (r=+0.743 and +0.772 respectively). CONCLUSION: Raised level of Il-6 and TNF-alpha may influence the development of anemia in Egyptian patients with Lupus Nephritis.