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

Abstract

Cadmium (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.

Cytoprotective effects of dietary flavonoids against cadmium‐induced toxicity

“…showed that Cd decreased FSH levels and reduced LH secretion in the pituitary, thus reducing generation of T . Other studies have shown that Cd increased the levels of LH, FSH, and T in developmental rats . This may be related to exposure routes, doses, times, and the different types of experimental animals used.…”

“…Flavonoids had anti‐inflammatory and antifibrosis effects in the liver . Studies have showed that flavonoids could inhibit the levels of iNOS and COX‐2, promote the vitality of lymphocytes, increase IL‐4 content, and decrease NO content by directly reacting with NO .…”

Nonsteroidal Anti‐Inflammatory Therapy: A Journey Toward Safety

“…Animal studies also suggested that it may be valuable for the treatment of degenerative and chronic conditions, such as Duchenne muscle dystrophy and benign prostatic hyperplasia . Furthermore, this botanically based mixture appears to exert a protective action in cadmium‐induced testicular toxicity and gentamicin‐induced nephrotoxicity . Finally, flavocoxid exhibited neuroprotective effects in rodent models of cerebral ischemia, autoimmune encephalomyelitis, and brain injury …”

Exposure to Cadmium Impairs Sperm Functions by Reducing CatSper in Mice

“…Cadmium, which is one of the most common environmental and occupational metallic toxicants, has also been demonstrated to potentially threaten human health [1-3]. Due to its high toxicity and cumulative effect, Cd easily leads to multi-organ injury, especially to the genital system [4-6]. Compared with other organs, the testes, which are the male gonads, are more vulnerable to toxicants because of their active cell division and metabolism [7-11].…”