ACUTE TOXICITY OF DIFFERENT SIZES OF SILVER NANOPARTICLES INTRAPERITONALLY INJECTED IN BALB/C MICE USING TWO TOXICOLOGICAL METHODS

Objective: This study aimed to evaluate the acute toxicity of intraperitoneally administrated silver nanoparticles (AgNPs) with different particle sizes in BALB/c mice.Methods: Citrate-capped AgNPs were prepared by citrate reduction method and isolated into small particles (average size 20 nm) and large particles (average size 50 nm). The median lethal dose (LD50) of 20 nm and 50 nm AgNPs was estimated using two toxicological methods, classical Dixon's up-and-down method and AOT425statPgm method for up-and-down procedure.Results: The LD50 was evaluated at the dosage level of 169 and 213.8 mg/kg, respectively for 20 nm AgNPs and at the dosage level of 354 and 391.5 mg/kg, respectively for 50 nm AgNPs. The results showed that LD50 obtained by the AOT425statPgm method was in accord with that of the Dixon's method and no significant differences between them (P = 0.06). The size 20 nm AgNPs were more toxic than the size 50 nm AgNPs. The behavioural responses and deviations were dose dependent, increasing by increasing the dose. The anatomical examinations showed that AgNPs were mainly accumulated in liver and spleen of dosed mice.Conclusion: The results suggested that the AOT425statPgm method was an efficient tool and a good alternative method for use in future acute toxicity studies.Â

Effect of Experimental Phenylketonuria on the Bone of Pregnant Mothers and Their Young During Perinatal Life and After Delivered Newborn of Albino Rats

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha-methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after the 6th day of onset of gestation till 14 & 16 days of gestation as well as at parturition. Treatment with alpha-methylphenylalanine/ phenylalanine resulted in a significant decrease of accumulated body weight gain during pregnancy as well as exhibited marked growth retardation of prenatal fetuses and delivered newborn. The growth retarded fetuses was manifested by decreased body weight, malformed both fore- & hindlimb, oedematous skin & superficial hematomas widely spread in different parts of the body. Ossification of bones was greatly altered. Skeletal abnormalities restricted mainly in skull, sternebrae, lumbar, caudal vertebrae and distal phalanx of both fore- & hindlimb. Histological examination of femoral bone revealed varieties of histopathological abnormalities which illustrated and discussed. These results suggested that exposure of the fetus to high plasma concentrations of phenylalanine cause deformities of bone

Histopathological Effects on the Eye Development During Perinatal Growth of Albino Rats Maternally Treated with Experimental Phenylketonuria During Pregnancy

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal brain development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha-methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after 6th day of onset of gestation till 14 & 16 days prenatal as well as at parturition. Treatment with alpha-methylphenylalanine resulted in significant reduction of retinal cell layers of prenatal fetuses and delivered newborns.   Histological abnormalities were detected manifested by either hyaline degeneration of lens structure or inducing lens cataract as well as comparative atrophy of retina associated with the development of Malignant polypoid mass in the ganglionic cell layers in contact with the lens

Histopathological Effects on the Eye Development during Perinatal Growth of Albino Rats Maternally Treated with Experimental Phenylketonuria during Pregnancy

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal brain development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha-methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after 6th day of onset of gestation till 14 & 16 days prenatal as well as at parturition. Treatment with alpha-methylphenylalanine resulted in significant reduction of retinal cell layers of prenatal fetuses and delivered newborns.   Histological abnormalities were detected manifested by either hyaline degeneration of lens structure or inducing lens cataract as well as comparative atrophy of retina associated with the development of malignant polypoid mass in the ganglionic cell layers in contact with the lens

Effect of Experimental Phenylketonuria on the Bone of Pregnant Mothers and their young during Perinatal Life and after Delivered Newborn of Albino Rats

Phenylketonuria (PKU) is a genetic disorder that is characterized by an inability of the body to utilize the essential amino acid, phenylalanine. The disease results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine to tyrosine. Although, this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known about the mechanisms involved in the pathology of PKU during neonatal development. Elevated concentrations of plasma phenylalanine were induced in pregnant rats by oral administration of 50mg/100g body weight alpha-methylphenylalanine plus phenylalanine supplementation at a dosage of 60mg/100g body weight two times daily after the 6th day of onset of gestation till 14 & 16 days of gestation as well as at parturition. Treatment with alpha-methylphenylalanine/ phenylalanine resulted in a significant decrease of accumulated body weight gain during pregnancy as well as exhibited marked growth retardation of prenatal fetuses and delivered newborn. The growth retarded fetuses was manifested by decreased body weight, malformed both fore- & hindlimb, oedematous skin & superficial hematomas widely spread in different parts of the body. Ossification of bones was greatly altered. Skeletal abnormalities restricted mainly in skull, sternebrae, lumbar, caudal vertebrae and distal phalanx of both fore- & hindlimb. Histological examination of femoral bone revealed varieties of histopathological abnormalities which illustrated and discussed. These results suggested that exposure of the fetus to high plasma concentrations of phenylalanine cause deformities of bone

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

Fine structure of the stinger, histology and histochemistry of the venom gland in the scorpion Androctonus amoreuxi (Buthidae)

The venom apparatus of the scorpion Androctonus amoreuxi has been identified histologically and histochemically in the present study. The results showed that this apparatus composed of a pair of venom glands and a stinger located in the terminal segment called telson. The stinger of the venom apparatus has been studied by the light microscope and SEM. The stinger, located at the end section of the telson, is sickle-shaped. The venom is ejected through a pair of venom pores on its subterminal portion. Both venom ducts extend along the stinger without contact with each other since they are separated by connective tissue cells. The stinger is covered by cuticle and spines. Each venom gland is covered by a sheath of striated muscle and is lined with extensively folded secretory epithelium that consists of non-secretory and secretory venom-producing cells. The venom-producing cells reacted positively to histochemical tests for carbohydrates and proteins. The outcomes also revealed that the venom-producing cells of both glands produce neutral mucosubstances. The structure and secretion of scorpion venom glands are discussed within the context of the present results