No abstract

Heavy metals including mercury, cadmium, cobalt, and copper (100 microM) exerted an adverse effect on the viability of isolated rat adrenal capsular (zona glomerulosa), adrenal decapsular (fasciculata and reticularis), and Leydig cells of the testis, with mercury being the most potent. Due to the decreased cell viability there was a parallel reduction in corticotropin-stimulated corticosterone production by adrenal decapsular cells and luteinizing hormone-stimulated testosterone production by Leydig cells. The results indicated a direct toxic action of these heavy metals on steroid-producing cells in the adrenal gland and the testis. Other metals tested, including lead, zinc, aluminum, chromium, iron, nickel, and lithium, did not exert any deleterious effect on cell viability or hormone-induced steroidogenesis in adrenal and Leydig cells when tested up to a concentration of 100 microM.

The present study has demonstrated a differential cytotoxicity of stellettin A (1) between human leukemia HL-60 cells (IC50 0.4 microg/mL) and human prostate cancer LNCaP cells (IC50 120 microg/mL). Treatment of cells with 1 revealed the activation of NADPH oxidase, the dramatic generation of reactive oxygen species, and the dissipation of mitochondrial membrane potentials, with HL-60 cells being more sensitive than LNCaP cells by an order of magnitude. Immunoblotting analysis further demonstrated a stronger upregulation of the apoptosis marker proteins, FasL and caspase-3, in HL-60 cells, and pretreatment of cells with antisense oligonucleotide for caspase-3 abolished apoptosis. All available evidence suggests that 1 induces oxidative cell death through a FasL-caspase-3-apoptotic pathway.

Male C57 mice kept under a 14:10 (L:D) photoperiod received vehicle (VEH), melatonin (MEL) and methoxytryptamine (MTA) in the drinking water for 2 weeks. Splenocytes from MEL-treated mice showed an augmented mitogenic response to concanavalin A and lipopolysaccharide (LPS) while splenocytes from MTA-treated mice demonstrated an enhanced mitogenic response to LPS when compared to the VEH-treated control. Splenocytes from MEL-treated and MTA-treated mice also produced higher levels of gamma interferon and interleukin-2. Lymphokines prepared from splenocytes of MEL-treated mice stimulated peritoneal macrophages to produce more nitrite than those from splenocytes of MTA-treated and control mice, suggesting that MEL had a stronger stimulating effect on the lymphocytes than MTA. Understimulation of lymphokines from MEL-treated mice, peritoneal macrophages from MTA-treated mice produced a greater inhibition of the growth of murine mastocytoma P815 cells than that produced by macrophages from control and MEL-treated mice, suggesting that MTA was more potent than MEL in rendering the macrophages responsive to lymphokines. The results point to immunostimulatory actions of the pineal indoles MEL and MTA.

It is well documented that hypothyroid patients are more susceptible to microbial infections. In order to study whether this impaired response is due to a decrease in production of antitumor molecules or an impaired ability to transmit information in the macrophage, a hypothyroid animal model was used to study the expression of both tumor necrosis factor gene and c-fos protooncogene in peritoneal macrophages. Inbred mice were rendered hypothyroid by an antithyroid drug, methimazole, and the expression of tumor necrosis factor gene and c-fos protooncogene in peritoneal macrophages were studied. Impairment of c-fos and TNF genes were at both transcriptional and translational levels using northern blot analysis, bioassays, and immunocytochemical staining methods. These results indicate that the reduction in signal transduction and in the production of antitumor molecules may cause the poor defense ability of hypothyroid animals.