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

Dietary soy isoflavones during pregnancy suppressed the immune function in male offspring albino rats

Phytoestrogens have an impact on both animals and humans due to use of legumes in animal diets as well as the increase of vegetarian diets in some human populations. Phytoestrogens thought to have varieties of adverse effects, among which immune system was involved. The present study aimed to investigate the effect of prenatal exposure to dietary soy isoflavones on some immunological parameters in male albino rat offspring. The pregnant rats were divided to three groups (12/group). Control group (free soy isoflavones), low soy isoflavones group (6.5%) and high soy isoflavones group (26%). The male offspring cell-mediated immune response was determined using phytohemagglutinin (PHA) injection and the intumesce index which was calculated on postnatal day 50 (PND 50). At PND 50, blood samples were collected for interleukin 12 (IL-12), interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) determination. Spleen, thymus, and PHA injected footpads were fixed for histopathology. Intumesce index, IL-12, IFN-γ, spleen and thymus relative weights were significantly (P < 0.05) decreased in offspring born to dams fed low and high dietary soy isoflavones. In contrary, TNF-α was significantly (P < 0.05) increased in offspring born to dams fed high dietary soy isoflavones. Spleen of rats born to dams fed high dose of dietary soy isoflavones showed coagulative necrosis in white pulp. In conclusion, male offspring born to dams fed different levels of soy isoflavones showed marked immunosuppression after PHA stimulation. This effect was mediated through the reduced IFN-γ that interacts with the IL-12 production pathway. Keywords: Isoflavones, Pregnancy, Immunological responses, Rat

The Reno and Hepatoprotective Effects of SAMWA Plant (Cleome droserifolia) Methanolic Extract against Adrenaline-Induced Adverse Effect to Male Rats

Adrenaline is widely used drug to combat several conditions such as allergy and anaphylaxis. The current work was to investigate the renal and hepatic complications following adrenaline injection, in addition, the impact of Cleome (SAMWA) methanolic extract on adrenaline- induced renal and hepatic alterations. Twenty-four male Wister rats were divided equally into four groups; Normal control group received oral distilled water for 30 consecutive days and administered subcutaneous saline on the 31st and 32nd days. The Cleome extract (200 mg/kg) group received Cleome methanolic extract (200 mg/kg, P.O) for 30 consecutive days and administered subcutaneous saline on the 31st and 32nd days. The adrenaline group received distilled water orally for 30 consecutive days and administered subcutaneous adrenaline (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. Cleome extract (200 mg/kg)/ adrenaline received Cleome methanolic extract (200 mg/kg, P. O) for 30 consecutive days and administered subcutaneous adrenaline (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. Liver and kidney function biomarkers in addition to histopathological analyses were evaluated. Adrenaline caused alteration in liver and kidney function biomarkers without affecting the histological structure of the liver and the kidney. SAMWA methanolic extract pretreatment significantly decreased serum urea, uric acid, aspartate aminotransferase (AST), alanine transaminase (ALT) and Alkaline Phosphatase (ALP). SAMWA ameliorated serum albumin reduction and total protein induced by adrenaline injection. SAMWA methanolic extract could protect liver and kidney of rats exposed to adrenaline