Irit Gil-ad, PhD, Blana Shtaif, MSc, Rina Eshet, PhD, Rachel Maayan, PhD, Moshe Rehavi, PhD and Abraham Weizman, MD
Background: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) have been reported to possess neuroprotective as well as anti-tumoral activity in vitro and in vivo.
Objectives: To compare the effect of the two neurohormones on cell viability in primary whole-brain fetal mouse culture and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK-N-SH).
Methods: Cell viability and cell proliferation were determined with the neutral red and 3H-thymidine uptake methods, Apoptosis in propidium iodide-stained neuroblastoma cells was determined using flow cytometry.
Results: DHEA (1 nM-10 ìM) decreased the viability of selected primary neuronal cells (33-95% after 24 and 72 hours) but not of whole-brain cultured cells (neuron+glia). DHEAS did not significantly modify cell viability in either primary culture. In a human neuroblastoma cell line, DHEA (1 nM- 1 ìM) decreased 3H-thymidine uptake (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly modify, or only slightly stimulated, cell viability and uptake of 3H-thymidine (132% of controls). The combination of DHEA and DHEAS neutralized the toxic effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100 nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and 26.3%. respectively, vs. control 2.54%).
Conclusions: Our results do not confirm a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a differential role: DHEA possesses a neurotoxic (expressed only in isolated neurons) and anti-proliferative effect DHEAS demonstrates only a slight neuroprotective effect.
Gabriel Kenet, MD, Joram Wardi, MD, Yona Avni, MD, Hussein Aeed, PhD, Haim Shirin, MD, Liliana Zaidel, MD, Rami Hershkovitz, MD and Rafael Bruck, MD
Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hypnotic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.
Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.
Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.
Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalidomide) than the control group (iodoacetamide only). Histologically, colonic inflammation in the treated group was markedly decreased.
Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.
Yuval Gielchinsky, MD, Deborah Elstein, PhD, Ayala Abrahamov, MD and Ari Zimran, MD
Taha Rashid, MBChB, Harmale Tiwana, PhD, Clyde Wilson, PhD and Alan Ebringer, MD
Yehuda Shoenfeld, MD, Yair Levy, MD and Pnina Fishman, PhD
Daniel Schapira, MD, DSc, Alexandra Balbir-Gurman, MD, Alicia Nachtigal, MD and Abraham Menachem Nahir, MD, PhD