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

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.

Inventory of Medicinal Plants Used Traditionally to Manage Kidney Diseases in North-Eastern Morocco: Ethnobotanical Fieldwork and Pharmacological Evidence

“…The dominated families that have been used to treat and relieve renal disorders were the Asteraceae (14 species), followed by the Lamiaceae (12 species), the Apiaceae (10 species), Rutaceae, Poaceae and Fabaceae (5 species) each, Cucurbitaceae with (4 species), Rosaceae, Myrtaceae, Brassicaceae and Amaranthaceae with (3 species for each), while the other families represent less than three species ( Figure 1 ). The predominance of Asteraceae, Lamiaceae, and Apiaceae, has already been proven in several ethnobotanical studies carried out in other Moroccan regions [ 14 , 22 , 23 , 24 ], as well as in other countries such as Turkey [ 25 ] and Italy [ 26 ]. Furthermore, the predominance of these plant families has already been confirmed in the results of specific ethnobotanical work for kidney disorders conducted in the Moroccan territory [ 17 , 22 , 27 ].…”

“…The predominance of Asteraceae, Lamiaceae, and Apiaceae, has already been proven in several ethnobotanical studies carried out in other Moroccan regions [ 14 , 22 , 23 , 24 ], as well as in other countries such as Turkey [ 25 ] and Italy [ 26 ]. Furthermore, the predominance of these plant families has already been confirmed in the results of specific ethnobotanical work for kidney disorders conducted in the Moroccan territory [ 17 , 22 , 27 ]. On the other hand, these botanical families dominate the Moroccan flora and are also almost omnipresent in the Moroccan territory [ 28 ].…”

Toxicological study on methanol root bark extract ofAcacia sieberiana(Fabaceae) in Wistar rats

“…The renal system plays an essential function in regulating key physiological activities, including acid-base balance regulation and fluid and electrolytes maintenance (Bencheikh et al, 2021).…”

Histopathology of Nephrotoxicity Associated with Administered Water Extract Purple Sweet Potato (<i>Ipomoea batatas</i>) in Mice (<i>Mus musculus</i>) in Stratified Phases of Dose

“…Furthermore, this histoarchitecture improvement is comparable to that of the control group. 28 Administering water extract purple sweet potato can be used as an alternative treatment by paying attention to the appropriate dose. Further research needs to be done by increasing the dose of use that can cause mortality.…”