The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation.

Noureddine Bencheikh,Imane Es-Safi,Mohammed Choukri,Bruno Eto,Omkulthom Mohamed Al Kamaly,Ahmed Dahmani,Soufiane El Assri,Hamza Mechchate,Mohamed Bnouham,Sabir Ouahhoud,Mostafa Elachouri,Loubna Kharchoufa,Mohamed Bouhrim

doi:10.3390/molecules26164806

Abstract

Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.

Highlights

Kidney function is essential for maintaining the overall hemostasis of our body
Ten phenolic compounds were found in the aqueous extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) using the HPLCDAD method (Table 1 and Figure 1)
The minimal concentration was reported for hydroxytyrosol 2.21 μg/mL (Table 1)

Summary

Introduction

Kidney function is essential for maintaining the overall hemostasis of our body This vital organ participates in the equilibrium of several important physiological functions such as detoxification, regulation of the acid-base and hydro-mineral balance, the regulation and the synthesis of some hormones, in particular, the erythropoietin necessary for the hematite synthesis, and blood pressure regulation [1]. By these facts related to these multiple functions, especially the detoxification property, the kidneys remain the most exposed organ in our body to different xenobiotics.

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