Retracted: Research Article Flavocoxid Protects Against Cadmium-Induced Disruption of the Blood-Testis Barrier and Improves Testicular Damage and Germ Cell Impairment in Mice

• DOI: 10.1093/toxsci/kfv185
• Publication Date: 2015-10-14T01:38:03Z
• Authors: Letteria Minutoli; Antonio Micali; Antonina Pisani; Domenico Puzzolo; Alessandra Bitto; Mariagrazia Rinaldi; Gabriele Pizzino; Natasha Irrera; Federica Galfo; Salvatore Arena; Giovanni Pallio; Anna Mecchio; Antonino Germanà; Daniele Bruschetta; Rosaria Laurà; Carlo Magno; Herbert Marini; Francesco Squadrito; Domenica Altavilla
• Keywords: Male; 0301 basic medicine; Cadmium Poisoning; 0303 health sciences; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Seminiferous Tubules; Cadherins; flavocoxid, seminiferous tubules, germ cells, p-ERK 1/2, TNF-alpha; Antioxidants; Catechin; 3. Good health; Mice, Inbred C57BL; Drug Combinations; Oxidative Stress; 03 medical and health sciences; Occludin; Animals; Lipid Peroxidation; Phosphorylation; Spermatogenesis; Protein Processing, Post-Translational; Biomarkers; Blood-Testis Barrier; Infertility, Male

AbstractCadmium (Cd) causes male infertility. There is the need to identify safe treatments counteracting this toxicity. Flavocoxid is a flavonoid that induces a balanced inhibition of cyclooxygenase (COX)-1 and COX-2 peroxidase moieties and of 5-lipoxygenase (LOX) and has efficacy in the male genitourinary system. We investigated flavocoxid effects on Cd-induced testicular toxicity in mice. Swiss mice were divided into 4 groups: 2 control groups received 0.9% NaCl (vehicle; 1 ml/kg/day) or flavocoxid (20 mg/kg/day ip); 2 groups were challenged with cadmium chloride (CdCl2; 2 mg/kg/day ip) and administered with vehicle or flavocoxid. The treatment lasted for 1 or 2 weeks. The testes were processed for biochemical and morphological studies. CdCl2 increased phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2, tumor necrosis factor (TNF)-α, COX-2, 5-LOX, malondialdehyde (MDA), B-cell-lymphoma (Bcl)-2-associated X protein (Bax), follicle-stimulating hormone (FSH), luteinizing hormone (LH), transforming growth factor (TGF) -β3, decreased Bcl-2, testosterone, inhibin-B, occludin, N-Cadherin, induced structural damages in the testis and disrupted the blood-testis barrier. Many TUNEL-positive germ cells and changes in claudin-11, occludin, and N-cadherin localization were present. Flavocoxid administration reduced, in a time-dependent way, p-ERK 1/2, TNF-α, COX-2, 5-LOX, MDA, Bax, FSH, LH, TGF-β3, augmented Bcl-2, testosterone, inhibin B, occludin, N-Cadherin, and improved the structural organization of the testis and the blood-testis barrier. Few TUNEL-positive germ cells were present and a morphological retrieval of the intercellular junctions was observed. In conclusion, flavocoxid has a protective anti-inflammatory, antioxidant, and antiapoptotic function against Cd-induced toxicity in mice testis. We suggest that flavocoxid may play a relevant positive role against environmental levels of Cd, otherwise deleterious to gametogenesis and tubular integrity.