Lactational exposure effect of polychlorinated biphenyl on rat Sertoli cell markers and functional regulators in prepuberal and puberal F1 offspring.

PURPOSE: Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants acting as endocrine disruptors. Many researches evidenced that PCBs affect the male reproductive system in adult rats and it can transfer from mother to offspring through milk. We investigated whether the lactational exposure to PCBs affects the Sertoli cell function in F1 offspring. METHODS: Dams were orally treated with different doses of PCB-Aroclor 1254 (1, 2 and 5 mg/kg bw/day, respectively) from postpartum day 1-20. Male offspring rats were killed on PND 21 and PND 60. Testes were used both for histological study and to isolate Sertoli cell. Serum and testicular interstitial fluid (TIF) levels of testosterone, ABP and estradiol were analyzed by ELISA method. The mRNA and protein expressions of follicle-stimulating hormone (FSHR), androgen-binding protein (ABP), Inhibinß, androgen receptor (AR) and estrogen receptor (ERß) were studied using real-time PCR and immunoblotting, respectively. RESULTS: The testicular architecture was altered in PCB-treated groups of both prepuberal and puberal rats. Testosterone, estradiol and androgen-binding protein levels were altered in both serum and TIF in PCB treated groups. The gene expression level of FSHR, ABP, ERß and AR was decreased in a dose-dependent manner, whereas Inhibinß gene expression level was increased in PCB-treated groups. CONCLUSION: Lactational exposure to PCB affects both the histoarchitecture of testis, Sertoli cell maker and functional regulators in both prepuberal and puberal F1 male progeny.

Lactational exposure of polychlorinated biphenyls downregulates critical genes in Leydig cells of F1 male progeny (PND21).

Polychlorinated biphenyls (PCBs) are environmental contaminants. The present study was aimed to test the effect of lactational exposure of PCBs on Leydig cellular mRNA and protein expressions of 5α-reductase, aromatase and androgen receptor (AR) in F1 male offspring. Lactating dams were orally gavaged with different doses of PCBs (Aroclor 1254) 0, 1, 2 and 5 mg kg b.wt-1  day-1 , respectively, from PND1 to PND21. Male offsprings were sacrificed at PND21. Testes were used to isolate Leydig cells. Blood was collected. Serum testosterone (T) and oestradiol (E2 ) were measured. Anogenital distance was measured. Dams' milk lipid and serum lipids of male pups were estimated. PCB (Aroclor 1254) concentration of dams' milk and serum of male pups were analysed by GC-ECD. Leydig cellular mRNA and protein expressions of 5α-reductase, aromatase and AR were significantly decreased. Our data suggest that lactational exposure of PCBs downregulates selected genes in Leydig cells of F1 generation on post-natal day 21.

Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)-Exposed Adult Male Rats.

Various epidemiological survey suggests that the central nervous system is the target for many environmental contaminants. One among them is Aroclor 1254, a mixture of polychlorinated biphenyls (PCBs) which explore a spectrum of biochemical and neurotoxic responses in humans and laboratory animals. Learning and motor coordination deficits are the profound effects of PCBs which may be related to cerebral dysfunction. The aim of the study is to elicit the protective effect of melatonin (Mel), a potent, blood brain permeable antioxidant against the effect of Aroclor 1254 on the signaling of glutamate-principal excitatory neurotransmitter and brain derived neurotrophic factor (BDNF) in the cerebral cortex of adult rats which plays a key role in brain functions. Adult male Wistar rats were grouped into four and treated intraperitonealy (i.p) Group I with corn oil (Control), Group II with PCBs (2 mg/kg/bwt), Group III with PCBs + Mel (2 mg/kg/bwt + 5 mg/kg/bwt) and Group IV with Mel (5 mg/kg/bwt). The protein expression of glutamate signaling molecules and mRNA expressions of GLAST, BDNF signaling molecules were analyzed. The results suggest that simultaneous melatonin treatment significantly attenuated the NMDA receptor mediated glutamate excitotoxicity and protects the inhibition of BDNF signaling caused by PCBs exposure in cerebral cortex of adult male rats. Schematic pathway illustrating the proposed mechanism by which melatonin protects against A1254 mediated glutamate induced neurodegeneration in the cerebral cortex of adult male rats. PCBs induced neurodegeneration is caused by the overactivation of NMDAR, followed by the activation of voltage dependent calcium channels leading to the increase in intracellular Ca(2+) that stimulates calpain. Calpain inturn inhibits the PKA α and neurtrophin BDNF, its receptor and downstream signaling MAPK pathway leading to neurodegeneration. Melatonin had scavenged the ROS produced by PCBS and decreased the NMDAR expression which inturn protected the cells from neurodegeneration.

Anti-cancer activity of quercetin in neuroblastoma: an in vitro approach.

Neuroblastoma is a neuroendocrine tumour derived from neural crest cells and it remains a major therapeutic challenge in pediatric oncology. As response rates to chemotherapy are low, surgery remains the only effective treatment but since many tumors have metastasized at the time of diagnosis, curative surgery is rarely achieved. Consequently, a substantial need for new therapeutic options emerges. Quercetin a flavonoid, has been reported to lower the risk of several cancers. This study was designed to investigate its effects on apoptosis induction in the N2a, a mouse neuroblastoma cell line. The cell viability was determined by dimethyl thiazolyl tetrazolium bromide assay and diamidino-2-phenylindole staining was performed to confirm the apoptosis. The gene expression of bcl-w, p53, p27 and protein expression of caspases (3 and 9), bax, cytochrome-c were studied. This in vitro outcome suggests that quercetin can be used as a potent anti-cancer drug in future.