RESUMEN
This study aims to evaluate the protective effect of grape seed proanthocyanidin extract (GSPE) on cadmium (Cd)-induced testicular apoptosis, endothelial nitric oxide synthases (eNOS) expression, and toxicity in rats. A total of 24 male Wistar rats were divided into four groups, namely, control, Cd (2.5 mg/kg), Cd + GSPE (100 mg/kg/day), and GSPE. Spermatogenesis and mean seminiferous tubule diameter were significantly decreased in the Cd groups. Furthermore, the GSPE-treated animals showed an improved histological appearance in the Cd group. The immunoreactivity of eNOS and the number of apoptotic cells were increased in Cd group. Our data indicate a significant reduction of terminal deoxynucleotide transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end-labeling staining and a decrease in the expression of eNOS in the testes tissue of the Cd group treated with GSPE therapy. Therefore, our results suggest that GSPE acts as a potent protective agent against Cd-induced testicular toxicity in rats.
Asunto(s)
Apoptosis , Intoxicación por Cadmio/fisiopatología , Suplementos Dietéticos , Extracto de Semillas de Uva/uso terapéutico , Infertilidad Masculina/prevención & control , Sustancias Protectoras/uso terapéutico , Testículo/patología , Animales , Antioxidantes/efectos adversos , Antioxidantes/química , Antioxidantes/uso terapéutico , Intoxicación por Cadmio/metabolismo , Intoxicación por Cadmio/patología , Suplementos Dietéticos/análisis , Extracto de Semillas de Uva/efectos adversos , Extracto de Semillas de Uva/química , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Infertilidad Masculina/etiología , Masculino , Necrosis , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo , Proantocianidinas/efectos adversos , Proantocianidinas/análisis , Proantocianidinas/uso terapéutico , Sustancias Protectoras/efectos adversos , Sustancias Protectoras/química , Distribución Aleatoria , Ratas Wistar , Túbulos Seminíferos/enzimología , Túbulos Seminíferos/metabolismo , Túbulos Seminíferos/patología , Espermatogénesis , Testículo/enzimología , Testículo/metabolismoRESUMEN
Protein kinase C (PKC) theta, a Ca(2+)-independent isoform of PKC, has been known to be expressed in skeletal muscle and T cells. In the present study, we isolated and characterized a smaller transcript expressed in the mouse testis, the cDNA of which is referred hereafter as PKCthetaII and the original PKCtheta as PKCthetaI. The cDNA clone of PKCthetaII has 2184 base pairs and 464 amino acids in the possible open reading frame, consisting of the 5' unique sequence of 20 amino acids and the PKCthetaI sequence of 444 amino acids. Genomic DNA analysis revealed that transcription of PKCthetaII is initiated from the PKCthetaII-specific exon, which is located between exons 7 and 8 of the PKCtheta gene, indicating that alternative splicing is the mechanism by which PKCthetaII is generated. PKCthetaII is expressed exclusively in the testis in an age-dependent manner with sexual maturation. In situ hybridization and reverse transcription-polymerase chain reaction of microdissected tissues clearly demonstrated that PKCthetaII is expressed in the seminiferous tubules of the mouse testis. Consistent with its molecular structure lacking the C1 regulatory domain, PKCthetaII is constitutively active as determined by an in vitro kinase assay, being independent of PKC activators, e.g. phosphatidylserine and phorbol ester. PKCthetaII may play a crucial role in spermatogenesis or some related function of the testis.