Secoisolariciresinol diglucoside protects against cadmium-induced oxidative stress-mediated renal toxicity in rats

J Trace Elem Med Biol. 2020 May 18:61:126552. doi: 10.1016/j.jtemb.2020.126552. Online ahead of print.

Abstract

Background: Cadmium is a well known environmental pollutant and strong toxic heavy metal, that causes oxidative damage to various organs of the body, including the kidney. Cadmium (II) chloride (CdCl2) is a water-soluble crystalline form, which exhibits a higher affinity with chlorides at the target site. The current study examined the protective effects of Secoisolariciresinol diglucoside (SDG), a principal lignan extracted from flaxseeds against CdCl2-induced renal toxicity in rats.

Methods: Twenty four healthy male Wistar rats with four groups of six animals each were used in the study. Group-1- Control was administered with saline. Group-2 -was treated with SDG; Group-3 with CdCl2 alone, and Group-4 were treated with CdCl2 plus SDG. The effect of Cd on kidney was assessed in terms of various parameters like lipid peroxidation, production of Nitric oxide (NO) and Myeloperoxidase (MPO), and kidney function markers like uric acid, urea, and creatinine. The levels of antioxidant molecules like glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also measured, apart from histopathological studies.

Results: The animals that received CdCl2, exhibited changes in the concentration of Cd in the kidney. The levels of kidney function markers like uric acid, urea, and creatinine were found to be abnormal in serum, and also there was a drastic decrease in the levels of glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The treatment of SDG significantly decreased (p < 0.05) the levels of NO and MPO in the animals treated with CdCl2 plus SDG when compared to the animal group treated with CdCl2 alone. The treatment of SDG before CdCl2 injection exhibited significant changes in the activity of the antioxidant enzymes, which was evidenced by the restoration in their activities, when compared to CdCl2 alone treated group (p < 0.05), as observed in the results of histopathology.

Conclusions: The findings of the present investigation suggested that SDG exhibited anti-oxidant, anti-apoptotic and renoprotective properties. Thus, SDG may act as a supramolecular binding component and naturally occurring metal chelating agent for metal cations like Cd2+. Therefore, flaxseed lignan-SDG can be used as a therapeutic agent against nephrotoxicity caused by cadmium. However, detailed future studies are needed to know the underlying mechanism of action of SDG against the Cd and other heavy metals induced nephrotoxicity.

Keywords: Antioxidant enzymes; Flaxseed lignan; Heavy metal; Nephrotoxicity; Secoisolariciresinol diglucoside.