1. NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele.
- Author
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Antonuccio P, Micali AG, Romeo C, Freni J, Vermiglio G, Puzzolo D, Squadrito F, Irrera N, Marini HR, Rana RA, Pallio G, and Minutoli L
- Subjects
- Animals, Caspase 1 genetics, Disease Models, Animal, Drug Therapy, Combination, Gene Expression Regulation drug effects, Humans, Interleukin-1beta genetics, Male, NLR Family, Pyrin Domain-Containing 3 Protein drug effects, Organ Size drug effects, Polydeoxyribonucleotides pharmacology, Rats, Selenomethionine pharmacology, Testosterone metabolism, Varicocele genetics, Varicocele metabolism, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Polydeoxyribonucleotides administration & dosage, Selenomethionine administration & dosage, Varicocele drug therapy
- Abstract
Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1β and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1β expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.
- Published
- 2021
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