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)

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 ۲ (PAR-۲) in this effect. Methods: Thirty-two male Balb/c mice divided randomly into four groups were either treated with saline, Gen (۲۲۵ mg/kg/i.p., daily from day ۳ to day ۱۰), Gen (۲۲۵ mg/kg i.p.) daily from day ۳ to day ۱۰ and DPSE (۱۰۰ mg/kg/p.o.) daily for ۱۰ days, or Gen (۲۲۵ mg/kg i.p.) daily from day ۳ to day ۱۰ and HM (۱۰۰ mg/kg/p.o., daily for ۱۰ days). Mice were sacrificed ۲۴ 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-۲ 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-۲. 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-۲ in Gen-induced renal toxicity as well as in the protective effects of the two tested natural products.