Protective Effect of Thymus serrulatus Essential Oil on Cadmium-Induced Nephrotoxicity in Rats, through Suppression of Oxidative Stress and Downregulation of NF-κB, iNOS, and Smad2 mRNA Expression.

Mohd Nazam Ansari,Faisal Imam,Najeeb Ur Rehman,Aman Karim,Abubaker M Hamad

doi:10.3390/molecules26051252

Abstract

The purpose of the research was to examine the protective effect of essential oil from Thymus serrulatus Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl2, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl2-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl2 significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action.

Highlights

Environmental chemical exposure remains a major public health problem globally.Exposure to cadmium (Cd), one of the most reactive toxic metals, has increased in the biosphere from both natural and anthropogenic sources [1]
Effect of TSA Oil on Biomarkers of Kidney Function The levels of blood urea, uric acid, creatinine, and blood urea nitrogen (BUN) were found to be significantly elevated (p < 0.01) in rats that were treated with Cd only (3 mg/kg, IP) for 7 days
GSH levels were significantly elevated in the TSA-oil- and silymarin-treated groups compared with the Cd group (Figure 2A,B)

Summary

Introduction

Environmental chemical exposure remains a major public health problem globally.Exposure to cadmium (Cd), one of the most reactive toxic metals, has increased in the biosphere from both natural and anthropogenic sources [1]. A significantly increased absorption along with decreased excretion rate leads to an increased burden of Cd in different organs. The Cd can damage multiple organs depending on its dose, route, and duration but mainly affects kidneys and causes renal impairment [3]. The kidneys are vital organs in the human body and responsible for various essential functions, including the removal of harmful metabolites, nitrogenous wastes, and some drugs with urine [4]. Earlier studies reported that Cd toxicity results in irreversible dysfunction of renal tubules [5] and causes decreased removal of the toxic chemicals, drugs, or both that lead to acute kidney failure. Renal injury caused by chronic Cd exposure may lead to chronic kidney failure and if not treated can result in death [6,7]. There have been studies of common abnormal effects of Cd on kidney function, but there is still a lack of detailed information on molecular mechanisms and a need to explore this further [8]

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