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J Herbmed Pharmacol. 2022;11(2): 286-295.
doi: 10.34172/jhp.2022.34

Scopus ID: 85129466262
  Abstract View: 1580
  PDF Download: 856

Original Article

Date palm seed extract and herbal mixture mitigate gentamicin-induced renal injury in mice: Role of Protease-activated receptors (PARs) and Retinoid X receptor alpha (RXR-α)

Suliman Sohaim 1 ORCID logo, Salman Mohammed 1 ORCID logo, Elham Amin 2, 3* ORCID logo, Hussein M Ali 1, 4 ORCID logo, Mohamed Abdelbakky 1, 5* ORCID logo

1 Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia
2 Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt
3 Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia
4 Department of Biochemistry, Faculty of Medicine, Al-Azhar University, Assiut 71524, Egypt
5 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 11751, Egypt
*Corresponding Authors: Email: elham_bns@yahoo.com; Email: m.abdelbakky@qu.edu.sa

Abstract

Introduction: Gentamicin (Gen) causes renal toxicity by inhibiting protein synthesis in kidney cells, causing proximal tubule cell necrosis and renal failure. Herein, we examined the nephroprotective effect of date palm seed extract (DPSE) and one herbal mixture (HM; composed of Tribulus terrestris, Aerva lanata, Andrographis paniculata, and Raphanus sativus) against Gen-induced renal toxicity in mice with special reference to the possible role of retinoid X receptor alpha (RXR-α) and protease-activated receptor 2 (PAR-2) in this effect. Methods: Thirty-two male Balb/c mice divided randomly into four groups were either treated with saline, Gen (225 mg/kg/i.p., daily from day 3 to day 10), Gen (225 mg/kg i.p.) daily from day 3 to day 10 and DPSE (100 mg/kg/p.o.) daily for 10 days, or Gen (225 mg/kg i.p.) daily from day 3 to day 10 and HM (100 mg/kg/p.o., daily for 10 days). Mice were sacrificed 24 hours after the last dose administration, and kidney tissues were dissected out, weighed, and subjected to histological, immunofluorescence, and biochemical assays. Results: The Gen-induced renal toxicity group demonstrated a significant decrease in RXR-α and a significant increase in PAR-2 protein expression. Treatment with DPSE or HM significantly improved Gen-induced effects on serum creatinine, blood urea nitrogen (BUN), white blood cells (WBCs), platelets, RXR-α extracellular matrix deposition, and PAR-2. Conclusion: The present study stated the nephroprotective effects of DPSE and HM and revealed, for the first time, the involvement of retinoid receptors and PAR-2 in Gen-induced renal toxicity as well as in the protective effects of the two tested natural products.

This work provides a comprehensive perception into the possible nephroprotective effect of date palm seed extract (DPSE) and one herbal mixture (HM) against gentamycin (Gen)-induced renal toxicity in mice and the possible role of RXR-α and protease-activated receptor 2 (PAR-2) in this effect. Hence, DPSE is a promising remedy against renal toxicity.
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Submitted: 17 Dec 2021
Revision: 10 Feb 2022
Accepted: 14 Feb 2022
ePublished: 01 Apr 2022
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