RESUMO
Within the last decade, several peptides have been identified according to their ability to inhibit the growth of microbial pathogens. These antimicrobial peptides (AMPs) are a part of the innate immune system of all living organisms. Many studies on their effects on prokaryotic microorganisms have been reported; some of these peptides have cytotoxic properties although the molecular mechanisms underlying their activity on eukaryotic cells remain poorly understood. Smp24 and Smp43 are novel cationic AMPs which were identified from the venom of the Egyptian scorpion Scorpio maurus palmatus. Smp24 and Smp43 showed potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards two acute leukaemia cell lines (myeloid (KG1-a) and lymphoid (CCRF-CEM) leukaemia cell lines) and three non-tumour cell lines CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HaCaT (human skin keratinocytes). Smp24 and Smp43 (4-256 µg/ml) decreased the viability of all cell lines, although HaCaT cells were markedly less sensitive. With the exception HaCaT cells, the caspase-1 gene was uniquely up-regulated in all cell lines studied. However, all cell lines showed an increase in downstream interleukin-1ß (IL-1ß) expression. Transmission electron microscope studies revealed the formation of cell membrane blebs and the appearance of autolysosomes and lipid droplets in all cell lines; KG1-a leukemia cells also showed the unique appearance of glycogen deposits. Our results reveal a novel mechanism of action for scorpion venom AMPs, activating a cascade of events leading to cell death through a programmed pyroptotic mechanism.
RESUMO
BACKGROUND: The target of this animal study was to clarify the influence of Copper oxychloride (COC) (at concentrations of 50, 100 and 200 mg/kg b.wt.) administration for ninety days on the brain tissues to evaluate its possible neurotoxicity. METHODS: Thirty male albino rats were divided up into control and four experimental groups. Group-II (rats were fed corn oil daily through oral gavage) and Group-III-A, Group-III-B, Group-III-C (rats were fed orally with COC in a dosage of 50 mg/kg, 100 mg/kg and 200 mg/kg b.wt., respectively, daily for ninety days. Various biochemical analyses and histopathological assessment of rat forebrain were investigated. RESULTS: the brains of the treated rats at the three chosen doses of COC recorded a significant (p≤0.05) elevation of lipid peroxidation. The measured brain lactate dehydrogenase (LDH) revealed non significant (p ≥ 0.05) differences among the studied groups. Besides, there was a significant (p < 0.05) decrease in the brain manganese concentration (Mn) of COC treated rats. In addition, there were significant (p< 0.05) increase in zinc (Zn) brain concentration and non significant change in copper (Cu) brain concentration among groups. The brain, cerebrum showed marked histopathological damage than cerebellum. The cerebral cortex of COC treated animals exhibited severe degenerative changes. CONCLUSION: The present results concluded that consumption of food contaminated even with modest amount of COC can enter the brain barrier resulted in neurotoxicity in the brain of albino rats.
