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Serotonin 5HT2A receptor antagonism mediated anti-inflammatory and anti-fibrotic effect in adriamycin-induced CKD in rats

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Abstract

A selective 5-HT2A 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-HT2A 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-HT2A, IL-6, TGF-β and collagen IV expression in renal tissue.

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Acknowledgments

The authors are grateful to Dr. Anshu Bansal (Technical Assistant) from Sophisticated Instrument Center (SIC) and Department of Pharmaceutical Sciences and Drug Research and to Punjabi University, Patiala, India, for supporting this study.

Funding

The Indian Council of Medical Research (ICMR) provided funding assistance for this study (Application no: 45/23/2018-PA/BMS/OL).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India

    Gagandeep Kaur & Pawan Krishan

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  1. Gagandeep Kaur
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  2. Pawan Krishan
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Both authors contributed to design this research work. Gagandeep Kaur has performed the experimental work as well as wrote the manuscript. Both the authors read, edited and approved this research article.

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Correspondence to Pawan Krishan.

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The authors declare that they have no conflict of interest.

Ethical clearance

The institutional animal ethics committee (IAEC) approved the experimental protocol used in the present study (Dated on 27th Feb, 2017; Meeting No 107/Go/ReBi/S/99/CPCSEA/2017–14 Protocol), and animals were provided by CCS Haryana Agriculture University, Hissar, Haryana and Central Animal Facility, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Mohali.

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Kaur, G., Krishan, P. Serotonin 5HT2A receptor antagonism mediated anti-inflammatory and anti-fibrotic effect in adriamycin-induced CKD in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1269–1279 (2020). https://doi.org/10.1007/s00210-020-01826-0

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