The efficacy of novel heterocyclic activators against mercuric chloride-induced acute renal failure in rats

Mercury chloride (HgCl 2 ) has a potent nephrotoxic effect. Synthesizing new heterocyclic steroids using some chemical strategies could be predictable to have promising efficiency against mercuric chloride-induced acute renal failure. Analytical and spectral data affirmed the structure of the unprecedented heterocyclic steroids. To assess their biological activities, rats were treated with tested compounds after HgCl 2 was intraperitoneally injected, a daily treatment for another 1 month. In comparison to the HgCl 2 group, synthesized compounds significantly prevented increased serum levels of creatinine, urea, renal lipid peroxidation, and nitric oxide levels, decreasing serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, tumor necrosis factor- -alpha, and interleukin-1 β levels and lipid profile concentration, and showed a significant increase in high-density lipoprotein and catalase levels. They, moreover, upregulated levels of Nephrin-2 and KIM-1 genes’ expression. Histopathological results supported our biochemical findings. Noteworthily, compounds 6 and 9 in particular have more antioxidant and anti-inflammatory activities than compounds 4 and 5 and play a salutary role against HgCl 2 toxicity. The biological characteristics of these new generations of heterocyclic steroid derivatives, which are demonstrated by their anti-inflammatory and antioxidant properties, could serve as a useful framework for the continued development of potent therapeutics.