R. vesicarius L. exerts nephroprotective effect against cisplatin-induced oxidative stress

Md Mahmudul Hasan,Ahmed M El-Shehawi,Most Sayla Tasmin,Md Abu Reza,Mona M Elseehy,Ariful Haque

doi:10.1186/s12906-021-03398-9

Abstract

BackgroundCisplatin is an outstanding anticancer drug, but its use has been decreased remarkably due to sever nephrotoxicity. R. vesicarius L. is a leafy vegetable that is evident with anti-angeogenic, anti-inflammatory, anti-proliferative, hepatoprotective, and nephroprotective potential. Therefore, this study was designed to inspect its methanol extract (RVE) for possible nephroprotective effect.MethodsPrimarily, in vitro antioxidant activity of RVE was confirmed based on 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging aptitude. Thereafter, Swiss Albino male mice were treated with cisplatin (2.5 mg/kg) for 5 successive days to induce nephrotoxicity. Recovery from nephrotoxicity was scrutinized by treating the animals with RVE (25, 50, and 100 mg/kg) intraperitoneally (i.p.) for the next 5 consecutive days. After completion of treatment, mice were sacrificed and kidneys were collected. Part of it was homogenized in sodium phosphate buffer for evaluating malondialdehyde (MDA) level, another part was used to evaluate gene (NQO1, p53, and Bcl-2) expression. Moreover, the hydrogen peroxide (H2O2) neutralizing capacity of RVE was evaluated in HK-2 cells in vitro. Finally, bioactive phytochemicals in RVE were determined using gas chromatography–mass spectrometry (GC-MS).ResultsRVE showed in vitro antioxidant activity in a dose-dependent fashion with 37.39 ± 1.89 μg/mL IC50 value. Treatment with RVE remarkably (p < 0.05) decreased MDA content in kidney tissue. Besides, the expression of NQO, p53, and Bcl-2 genes was significantly (p < 0.05) mitigated in a dose-dependent manner due to the administration of RVE. RVE significantly (p < 0.05) reversed the H2O2 level in HK-2 cells to almost normal. From GC-MS, ten compounds including three known antioxidants “4H-Pyran-4-one, 2, 3-dihydro-3,5-dihydroxy-6-methyl-”, “Hexadecanoic acid”, and “Squalene” were detected. The extract was rich with an alkaloid “13-Docosenamide”.ConclusionOverall, RVE possesses a protective effect against cisplatin-induced kidney damage.

Highlights

Oxidative stress is the result of disproportion between the formation of reactive oxygen species (ROS) and regular antioxidant defense mechanisms [1]
In-vitro antioxidant activity test Though previously R. vesicarius extracts (RVE) was reported for having antioxidant activity, we rechecked the antioxidant activity of our extract using DPPH free radical scavenging capacity
A recent study [39] showed that cisplatin significantly decreased expression of Bcl-2 in the kidney of mouse, but surprisingly we found elevated expression

Summary

Introduction

Oxidative stress is the result of disproportion between the formation of reactive oxygen species (ROS) and regular antioxidant defense mechanisms [1]. Oxygen-containing chemical species having reactive properties are known as ROS which includes free radicals and non-radical molecules such as superoxide and H2O2, respectively [3]. Oxidative stress induced by ROS is linked with the etiology of numerous diseases including cancer. The cellular and molecular events underlying AML include DNA damage, clonal propagation, increased cell death, and further genetic instability, which are the result of ROS-induced oxidative stress [4]. Human physiology has been gifted with numerous mechanisms that can generate antioxidants to exert protection against oxidative stress leading to protect cells from toxic effects and serve to disease prevention [5]. This study was designed to inspect its methanol extract (RVE) for possible nephroprotective effect

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