Diacerein Downregulates NLRP3/Caspase-1/IL-1β and IL-6/STAT3 Pathways of Inflammation and Apoptosis in a Rat Model of Cadmium Testicular Toxicity

Abstract

The potential gonadal protective effect of diacerein (DCN) and its underlying mechanisms were studied in a rat model of cadmium-induced testicular toxicity. The rats received DCN (50 mg/kg/day, p.o.) for 10 days and one injection of CdCl2 (2 mg/kg, i.p.) on day 9. Cadmium significantly declined serum testosterone and significantly raised interleukin-1β, interleukin-6, interleukin-18, tumor necrosis factor-α, caspase-1, phosphorylated signal transducer and activator of transcription-3 (pSTAT3), nuclear factor-κB p65, Bax, and caspase-3 in rat testes. DCN significantly ameliorated the changes in the biochemical measurements observed with CdCl2 insult. Additionally, DCN preserved the normal testicular architecture, maintained spermatogenesis, and lowered the expression of NOD-like receptor family protein 3 (NLRP3) inflammasome in testes of rats that received CdCl2. It was concluded that DCN significantly protected the gonads of male rats exposed to cadmium toxicity through modulation of NLRP3/caspase-1/IL-1β and IL-6/STAT3 pathways of inflammation and apoptosis.