Serotonin 5HT2A Antagonist Ameliorate Chronic Kidney Disease Progression by Reducing Glomerulosclerosis and Renal Fibrosis in Rodents
Introduction: 5-HT2A receptor antagonism has been proven to improve renal blood flow, kidney functional and structural parameters in numerous renal disease models. We aimed to investigate that Ketanserin can turn down bilateral I/R induced renal alterations or not by evaluation of various renal parameters along with expression levels of fibrotic, inflammatory genes and podocyte proteins.
Material and methods: CKD was induced by using a bilateral ischemia-reperfusion injury model (45 min) in Wistar rats. Subsequent 5-HT2A antagonist (Ketanserin) treatment (5 mg/kg/p.o) for 80 days.
Results:Ketanserin treatment demonstrated a significant change in oxidative stress, serum and urine parameters in bilateral I/R induced CKD rats. Furthermore, expression levels of 5HT2A ̴ 4.425-fold, pro-inflammatory marker (IL-6 ̴ 13.04-fold), fibrotic genes (TGF-β ̴ 18.06-fold, Collagen-IV̴ 17.7-fold and Kim-1 ̴ 13.57-fold), podocyte proteins (NPHS1 ̴ 0.75-fold and NPHS2 ̴ 0.83-fold) were significantly (p<0.0001) altered by Ketanserin treatment in bilateral I/R treated animals. Moreover, considerable structural changes were observed in histopathological studies in ketanserin treated CKD animals, and these results are further supported via quantification of glomeruli size, necrosis score (1.8±0.21) Glomerulosclerosis (23.0±1.3) and tubule-interstitial fibrosis (23.5±1.4).
Conclusion: In conclusion, Glomerulosclerosis, inflammation, renal fibrosis, oxidative stress reduced by 5-HT2A antagonism and, also, significant improvement was noticed in podocyte protein (NPHS2 and NPHS1) expression levels, renal functional and structural parameters in diseased rats.
Keywords - Chronic Kidney Disease, Ketanserin, Tubulointerstitial Fibrosis, Inflammation, Serotonin, Bilateral I/R.