Cytotoxic effects of Smp24 and Smp43 scorpion venom antimicrobial peptides on tumour and non-tumour cell lines

Smp24 and Smp43 are novel cationic AMPs identified from the venom of the Egyptian scorpion Scorpio maurus palmatus, having potent activity against both Gram-positive and Gram-negative bacteria as well as fungi. Here we describe cytotoxicity of these peptides towards three non-tumour cell lines (CD34+ (hematopoietic stem progenitor from cord blood), HRECs (human renal epithelial cells) and HACAT (human skin keratinocytes) and two acute leukaemia cell lines (myeloid (KG1a) and lymphoid (CCRF-CEM) leukaemia cell lines) using a combination of biochemical and imaging techniques. Smp24 and Smp43 (4–256 µg/mL) decreased the cell viability (as measured by intracellular ATP) of all cells tested, although keratinocytes were markedly less sensitive. Cell membrane leakage as evidenced by the release of lactate dehydrogenase was evident throughout and was confirmed by scanning electron microscope studies

Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death

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-1β (IL-1β) 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

Biochemical, Histological and Ultrastructural Studies on the Effect of Citric acid Supplementation on Aflatoxins-intoxicated Japanese Quail

For poultry farmers and quails producers’, one of the biggest challenges is dealing with natural diet contaminants like mycotoxins. Worldwide, mycotoxins are present in all feed sources, primarily in corn, and they significantly reduce the health, immune function, and performance of birds. For this purpose, the effect of citric acid (CA) supplement on contaminated diet with Aflatoxins (AFL) in the liver biochemical, histological, and ultrastructural studies of male Japanese quail (Coturnix coturnix). Influences of experimental diets were assessed in 3 replications of 6 birds each (n = 18 per treatment). Quails two weeks old were assigned into 4 equal groups. The control quails fed only basal diet, AFL group quails were given basal diet contaminated with 2.5 mg AFL/kg diet, citric group quails fed basal diet with 10 g citric acid/Kg, and AFL/citric group quails fed basal diet contaminated with 2.5 mg AFL /Kg and augmented with 10 g/Kg citric acid. After four weeks, feeding AFL to quails induced hepatotoxicity as evidenced by significant decline in body weight, serum albumin and total protein while it significantly increased serum ALT, and AST activities. AFL also induces liver oxidative stress by the elevation of lipid peroxidation and reducing GPx, ADH, SOD and catalase activities. Descriptive hepatic histological and ultrastructural alteration were also noted in the AFL group. Treatment with CA induced an increase in total protein, albumin, SOD, GPx, ADH and significantly decreased ALT and AST activities and MDA level. Moreover, it also improved the histological and ultrastructure alternations induced in the liver of AFL group. It was concluded that supplementation of CA into the AFL polluted diets lessened the adverse influences of AFL on quail’s liver