benzofurans and Nephritis

Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms.

Topics: Albumins; Animals; Antihypertensive Agents; Benzofurans; Blood Pressure; Blood Urea Nitrogen; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Hypertension, Renal; Immunohistochemistry; Interleukin-6; Kidney Glomerulus; Losartan; Male; NADPH Oxidases; Nephritis; Neuroprotective Agents; NF-kappa B; Rats; Rats, Inbred SHR; Transforming Growth Factor beta1

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured. Mice receiving PGE1 and iloprost had a significant delay in the onset of proteinuria and reduction in mortality at 40 weeks. The TSI treatment had no apparent effect on proteinuria or mortality. The amelioration of the nephritis was not associated with an alteration in immune complex deposition in survivors at 40 weeks. Although PGE1 and iloprost lessened the age related increase in urinary TX B2, increased the urinary 6 keto PGF1 alpha levels and the ratio of 6 keto PGF1 alpha to TX B2; so did the TSI. The PGE1 treated mice did experience a marked and persistent reduction in blood pressure but this was not observed in the iloprost- or the TSI-treated mice. All drugs tested reduced the age-related increase in thromboxane B2 but only the PGE1 and iloprost had a significant effect on the evolution of the nephritis.

Topics: 6-Ketoprostaglandin F1 alpha; Age Factors; Alprostadil; Animals; Benzofurans; Blood Pressure; Disease Models, Animal; Epoprostenol; Female; Iloprost; Lupus Nephritis; Mice; Mice, Inbred NZB; Mice, Inbred Strains; Nephritis; Proteinuria; Thromboxane B2; Vasodilator Agents