The effects of Salvia przewalskii total phenolic acid extract on immune complex glomerulonephritis.

CONTEXT: Salvia przewalskii Maxim. (Lamiaceae) is a Chinese herbal medicine that has long been used for the treatment of cardiovascular disease. OBJECTIVE: The study investigated the therapeutic efficacy of S. przewalskii total phenolic acid extract (SPE) on immune complex glomerulonephritis (ICG) in rats. MATERIALS AND METHODS: Sixty-two Wistar rats were randomized into six groups. ICG was induced in all groups except normal control group. SPE was administered intragastrically at 24 h intervals for 40 consecutive days. Urine protein (UP), total serum protein (TSP), serum albumin (SA), serum cholesterol (SC) and serum urea nitrogen (SUN) were measured one day before, on day 20 and 40 after SPE administration. On day 40 after SPE administration, the kidneys were removed and prepared into pathologic sections. In addition, kidney wet mass was measured for calculating the kidney wet mass coefficient (KWMC). RESULTS: UP excretion was reduced significantly on day 20 after SPE administration in all three SPE groups as compared with that in medium group, and this effect was observable continuously until 40 days after SPE administration. Compared with medium group, TSP and SA were increased in all three SPE groups after 40 days treatment, while SC and SUN were decreased. KWMC was decreased significantly in 100 mg/kg SPE group after 40 days treatment compared with that in medium group. Histopathologic analyses showed that renal inflammatory infiltration and kidney intumesce were alleviated in all three SPE groups. CONCLUSIONS: SPE may be a potential therapeutic drug for glomerulonephritis.

Curcumin alleviates immune-complex-mediated glomerulonephritis in factor-H-deficient mice.

Complement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective anti-inflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh(-/-)) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45·4 ± 7·5 versus 35·6 ± 5·1; albuminuria, 50·1 ± 7·1 versus 15·7 ± 7·1; glomerulonephritis, 2·62 + 0·25 versus 2 + 0·3, P < 0·05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19(+) B cells and the ratio of CD19 : CD3 cells (P < 0·05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-ß and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.

Treatment of experimental granulomatous uveitis by lipoxygenase and cyclo-oxygenase inhibitors.

Lens-induced granulomatous uveitis was produced in brown Norway rats. To determine the role of the lipoxygenase and cyclo-oxygenase products of arachidonic acid in the modulation of granulomatous uveitis, one group of experimental animals was treated with nafazatrom, while another group was treated with nordihydroguaiaretic acid (lipoxygenase inhibitors). Both resulted in significant attenuation of granulomatous inflammation, with reduced giant-cell infiltration into the choroid. In contrast, indomethacin (a cyclo-oxygenase inhibitor) therapy resulted in increased giant-cell formation. These findings suggest that the lipoxygenase and cyclo-oxygenase products of arachidonic acid play a role in the development of granulomatous uveitis and that such inflammation can be selectively suppressed by lipoxygenase inhibitors.

Ribavirin treatment in murine autoimmune disease. I. Therapeutic efficacy and effect on the immune response.

NZB/W F1 female mice were treated from 20 weeks of age with ribavirin (a broad spectrum antiviral drug), cyclophosphamide, or saline. Treatment with ribavirin (250 mg/kg twice weekly) prolonged survival from 9.8 to 18.5 months, reduced anti-DNA antibodies, and prevented proteinuria. Ability of ribavirin to prolong survival was dose related when given on a twice weekly schedule. However, daily ribavirin (25 mg/kg/day) was as effective as higher intermittent doses. Optimal ribavirin therapy was equal to cyclophosphamide treatment with regard to prolongation of survival. Ribavirin treatment did not significantly alter the body weight, hematocrit, WBC count, serum immunoglobulins, or Coombs reactivity. No alterations in either cellular or humoral immune responses were noted in NZB/W F1 or BALB/c mice treated for prolonged periods with ribavirin. The impressive therapeutic response to a broad spectrum antiviral agent seen in mice already manifesting immune complex nephritis provides a new therapeutic approach to the treatment of autoimmunity.