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

• Published in: Biological trace element research Vol. 195; no. 2; pp. 499 - 505
• Main Authors: Fouad, Amr A., Abdel-Aziz, Asmaa M., Hamouda, Azza A. H.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2020; Springer Nature B.V
• Subjects: Administration, Oral; Animal reproductive organs; Animals; Anthraquinones - administration & dosage; Anthraquinones - pharmacology; Apoptosis; Apoptosis - drug effects; BAX protein; Biochemistry; Biomedical and Life Sciences; Biotechnology; Cadmium; Cadmium chloride; Cadmium Chloride - administration & dosage; Cadmium Chloride - toxicity; Caspase; Caspase 1 - metabolism; Caspase-1; Caspase-3; Cytokines; Disease Models, Animal; Down-Regulation - drug effects; Gonads; IL-1β; Inflammasomes; Inflammation - drug therapy; Inflammation - metabolism; Injections, Intraperitoneal; Interleukin 18; Interleukin 6; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - metabolism; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Life Sciences; Male; Model testing; Necrosis; Neoplasms; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Nutrition; Oncology; Rats; Rats, Sprague-Dawley; Receptors; Rodents; Serum; Spermatogenesis; Stat3 protein; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Testes; Testis - drug effects; Testis - metabolism; Testosterone; Toxicity; Transcription; Transducers; Tumor necrosis factor-α; IL-6/STAT3; Testes; CdCl; NLRP3/caspase-1/IL-1β; Diacerein; CdCl2
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-019-01865-6

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 CdCl
2
(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 CdCl
2
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 CdCl
2
. 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.