Sebivo Ameliorated Fibrotic and Inflammatory Changes in Kidney and Heart in Animal Model of Chronic Kidney Disease

Chronic kidney disease (CKD) remains a major global health concern. Current treatments primarily delay disease progression and alleviate complications rather than targeting key mechanisms. This pilot study aimed to evaluate the antifibrotic and anti-inflammatory effects of Sebivo on kidney and heart tissues in a rat CKD model.

A total of 30 male Sprague-Dawley rats were randomly assigned to sham-operated control, CKD and CKD + Sebivo groups. CKD was induced by 5/6 nephrectomy and rats received no treatment, saline or Sebivo for 12 weeks after surgery. Serum levels of total and free p-cresyl sulphate (PCS), indoxyl sulphate (IS) levels, as well as creatinine and blood urea nitrogen (BUN) were measured at 8 and 12 weeks following administration. After 12 weeks of treatment, kidney and heart fibrosis were evaluated by histological analysis, while inflammatory and fibrotic markers were assessed by qRT-PCR and western blotting.

Sebivo significantly reduced total serum PCS levels in CKD + Sebivo group compared to CKD group at 12 weeks (4.17 ± 0.99 vs. 8.78 ± 0.01 μg/L, p < 0.001). Heart fibrosis was significantly reduced in CKD + Sebivo group compared to CKD group (22.44% ± 6.82% vs. 34.90% ± 1.47%, p < 0.05), with a similar trend observed in the kidney. Sebivo improved renal function as indicated by decreased BUN and creatinine levels. Additionally, TGF-β1 mRNA and the protein levels of IL-6, TGF-β1, TIMP-1 and COL1A1 were significantly decreased in the kidney following Sebivo treatment.

Sebivo demonstrated potential to improve renal fibrosis and function, likely through modulating fibrotic and inflammatory pathways, suggesting Sebivo as a novel therapeutic treatment for CKD.