Serotonin 5HT receptor antagonism mediated anti-inflammatory and anti-fibrotic effect in adriamycin-induced CKD in rats.

A selective 5-HT receptor antagonist ketanserin has been used preclinically to improve renal blood flow because of its beneficial effect on autoregulation in various chronic kidney disease models. Ketanserin might be able to turn down adriamycin-induced chronic kidney disease, which is characterized by renal fibrosis, inflammation and structural and functional changes in glomeruli. In the present study, we investigated whether ketanserin suppresses these renal alterations or not. Wistar rats were administered with a single dose of adriamycin (6 mg/kg/i.v), which leads to development of severe tubulointerstitial fibrosis with altered renal function. Subsequent ketanserin treatment (5 mg/kg/p.o) for 4 weeks shown significant change in oxidative stress, serum and urine parameters in adriamycin-induced chronic kidney disease rats. Additionally, results showed that mRNA expression of TGF-β and collagen IV, which are known to promote fibrosis via various signaling pathways involved in the progression of renal disease, was suppressed by ketanserin treatment. Furthermore, expression levels of 5-HT and pro-inflammatory marker IL-6 have also been reduced significantly after ketanserin administration in adriamycin-treated animals. Moreover, histopathological studies also reveal the considerable structural changes after ketanserin treatment, and these results are further supported via data obtained from the percentage of glomeruli size changes. In conclusion, ketanserin reduces renal fibrosis and inflammation in adriamycin-induced chronic kidney disease by suppressing 5-HT, IL-6, TGF-β and collagen IV expression in renal tissue.