Benzodiazepines belongs to one of the most commonly used anxiolytic and anticonvulsant drugs in the world. Full description of toxic effects on different organs is lacking for nearly all the current benzodiazepines. The aim of the current work was to study the immunologic and vascular changes induced by sub-chronic administration of alprazolam and clonazepam in non-stressed and stressed adult male albino rats. Forty-two adult male albino rats were divided into 6 groups (I): (Ia) Negative control rats, (Ib): Positive control rats received distilled water, (II): Stressed rats, (III): Non-stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (IV): Stressed rats received daily oral dose of clonazepam (0.5 mg/kg), (V): Non-stressed rats received daily oral dose of alprazolam (0.3 mg/kg). (VI): Stressed rats received daily oral dose of alprazolam (0.3 mg/kg). At the end of the 4th week, total leukocyte count (WBCs) and differential count were determined, anti-sheep RBC antibody (Anti-SRBC) titer and interleukin-2 (IL-2) level were assessed, thymus glands, lymph nodes, spleens and abdominal aortae were submitted to histopathological examination. Alprazolam was found to induce a significant increase in neutrophil count and a significant decrease in lymphocytes, anti-SRBC titer and IL-2 level with severe depletion of the splenic, thymal and nodal lymphocytes, accompanied by congestion and eosinophilic vasculitis of all organs tested in comparison to clonazepam treated rats. Stress enhanced the toxic effects. It was concluded that the immune system and blood vessels can be adversely affected to a greater extent by short-term chronic administration of alprazolam than by clonazepam, and these toxic effects are aggravated by stress.
Background: Phthalates are used as plasticizers in Polyvinyl chloride (PVC) plastics. The essential trace element selenium (Se) is the critical component of cellular antioxidant defense. It participates in the cellular antioxidant defense and helps in protection and repair of DNA and apoptosis. Objectives: the aim of this study was to assess the influence of di (2-ethylhexyl) phthalate (DEHP) on the male reproductive system in newborn and pubertal rats and to evaluate the effect of association between it and selenium on the development of male reproductive system. Design: forty adult pregnant female albino rats were utilized in this work (mating was performed and pregnancy was detected by daily vaginal swab). These animals were allocated randomly into four main groups. Group I (control group) received corn oil. Group ΙΙ: received diphthalates (DEHP) (150 mg/kg) by gavage daily from day 6 of gestation. Group IΙΙ: received sodium selenate (0.16mg/kg) from day 6 of gestation. Group IV: received (diphthalates (DEHP) 150 mg/kg + sodium selenate 0.16 mg/kg), daily from day 6 of gestation .After labour, the mother and the pups were categorized into 3 groups (a, b, c) according to the age of scarifying of the male newborn rats (postnatal day (PND) 1, PND21 "the age of weaning" and PND35 day which is the age of puberty). At the end of every stage of the experiment, 24 hours after the last administration, all animals were sacrificed and the testes were dissected out and subjected to histopathological, immunohistochemistry, and morphometrical examination. Results: Administration of DEHP at a dose of 150 mg/kg induced several histopathological changes in testes of albino rats as sloughed germinal epithelium and apoptosis of epithelial cells of seminiferous tubules in addition to delayed puberty. It significantly reduced tubular diameter and tubular epithelial height. The addition of selenium partially improved the state of apical processes of Sertoli cells as evidenced by vimentin immunohistochemistry. It also reduced the degree of apoptosis as evidenced by caspase-3 immunohistochemistry in addition to the improvement of tubular epithelial height. Conclusion: Exposure to DEHP led to pronounced testicular damage and impaired spermatogenesis in newborn and pubertal male rats. Recommendations: Many alternatives should be developed to improve the safety profile of the plasticizer or prevent its release from P-PVC devices especially medical ones.
Background: The potential application of ionizing radiation in medical practice and also, the potential accidental exposure to radiation enhanced the development of effective radio modifier. The aim of this work was to evaluate the possible protective role of individual and combined administration of Nigella sativa (NS) and vitamin E against the toxic effects of single 6 Gray (Gy) dose of gamma radiation on adult male albino rats Material and methods: ninty adult male albino rats were equally divided into 9 groups: Group SI: (-ve control), group SII (+ve control), group SIII: each rat was exposed to a single dose of radiation 6 Gy, group IV: each rat was gavaged orally with 0.6 ml NS dissolved in one ml distilled water once daily 5days/week, group SV: each rat was gavaged100 mg\kg vitamin E dissolved in one ml corn oil once daily 5days/week, group SVI: each rat received both vitamin E and NS orally in the same doses once daily for 5 days/week, group SVII: each rat received NS oil for 5days/week daily. At the 3 rd day, each rat was exposed to a single radiation in the previous doses, group SVIII: each rat received vitamin E daily for 5days/week, at the 3 rd day each rat was exposed to a single radiation in the same previous doses, group SIX: each rat received both vitamin E and NS daily for 5days/week. At the 3 rd day each rat was exposed to a single radiation in the previously mentioned doses. After 15 days from last exposure, rats of each group were submitted to estimation of complete blood count (CBC) and oxidative stress parameters, then the rats were sacrificed. The spleen and bone marrow of all rats were dissected and subjected to histopathological examination. Results: There was a significant deterioration in all measured parameters in irradiated group (group III). Upon supplementation with individual and combined NS and vitamin E before radiation, there were significant improvements in these measured parameters when compared with irradiated group. The histopathological changes in the spleen, in the form of white pulp depletion and multiple areas of hemorrhage. Bone marrow affection was also noticed, denoted by marked depletion of bone marrow tissue. Administration of individual and combined NS and vitamin E to irradiated rats induced an improvement, represented by the regression of the histopathological changes that occurred after radiation exposure. Biochemical and histopathological improvement in combined NS and vitamin E administration was more significant than that of individual NS and vitamin E administration. Recommendation: More efforts are needed to explore efficient natural combined radio protectors to limit deleterious effect of radiation.
Background: Atrazine (ATR) is one of the most commonly used triazine herbicides in the world. It was found that ATR can cause adverse effects on reproductive function in both genders of several mammalian and non-mammalian species. The aim of this work was to evaluate the pubertal hormonal disruption effects of atrazine herbicide during and after its sub-chronic administration in juvenile albino rats of both sexes. Material and methods: One hundred twenty six juvenile albino rats of both sexes were used. They were divided into 3 equal groups as follow: Group I (negative control group), group II (positive control group), group III (ATR group). Each group was subdivided equally into two subgroups; male rats (subgroup a) and female rats (subgroup b). Female rats were monitored daily for vaginal opening. At the end of the 3 rd and the 6 th week of the study, 7 rats of each subgroup were submitted to estimate the serum levels of estradiol and luteinizing (LH) hormones in all rats of both sexes in addition testosterone in male rats. Then the rats were sacrificed. The testis and epididiymis in males, uterus and ovary in females were dissected and subjected to histopathological examination. The remaining rats were left without intervention for another 3 weeks served as follow up group. Results: Atrazine was found to delay puberty in male rat presented by significantly decreased levels of testosterone level and increased in the estradiol levels, impaired spermatogenesis and decrease in number and size of Leydig cells with disorganization. It also was found to delay puberty in females denoted by delayed vaginal opening, underdevelopement of the uterus, impaired folliculogenesis and ovulation in the ovaries. Three weeks of follow up resulted in partial improvement. Recommendation: more efforts are needed to limit exposure to atrazine especially in ground and drinking water. Khayal, E.E.H.M.; et al….. Abarikwu, S.O.; Adesiyan, A.C.; Oyeloja, T.O.; Oyeyemi, M.O. and Farombi, E.O. (2010): Changes in sperm characteristics and induction of oxidative stress in the testis and epididymis of experimental rats by a herbicide, atrazine. Arch. Environ. Contam. Toxicol., 58:874-882. Abarikwu, S.O.; Pant, A.B. and Farombi, E.O. (2013): Quercetin decreases steroidogenic enzyme activity, NF-κB expression, and oxidative stress in cultured Leydig cells exposed to atrazine. Mol. Cell. Biochem., 373(1-2):19-28. Ackerman, F. (2007): The Economics of Atrazine. Int. J. Occup. Environ. Health,13:441-449. Adesiyan, A.C.; Oyeloja, T.O.; Abarikwu, S.O.; Oyeyemi, M.O. and Farombi, E.O.(2011): Selenium provides protection to the liver but not the reproductive organs in an atrazine-model of experimental toxicity. Exp. Toxicol. Pathol., 63(3): 201-207. Anderson, S. A.; Pearce, S. W.; Fail, P. A.; McTaggart, B. T.; Tyle, R. W. and Gray, L. E. (1995): Validation of the alternative reproductive test protocol to assess toxicity of methoxchlor in rats. Toxicol., 15: 164. Ashby, J.; Tinwell, H.; Stevens, J.; Pastoor, T. and Breckenridge, C.B. (2002): "The effec...
Background: Titanium dioxide (TiO2) is a white pigment that can be used in paints, coatings, plastics, papers, inks, medicines, pharmaceuticals, food products, cosmetics, and toothpaste. Titanium dioxide nanoparticles (TiO2 NPs) have been reported to elicit various adverse cellular effects including oxidative stress and DNA damage. N-acetylcysteine (NAC) is an antioxidant and free radical scavenger used to combat oxidative stress-induced damage in various tissues. Aim of the Work: is to study the toxic effects of TiO2 NPs oral administration and the protective role of NAC on the immune system of adult male albino rats. Thirty adult male albino rats were divided into 4 groups: Group I subdivided into: Subgroup (A): negative control. Subgroup (B): positive control received 1 ml of 5% gum acacia solution by oral gavage once daily. Group II: gavaged orally 100 mg/kg NAC once daily. Group III: gavaged orally 1200 mg/kg titanium dioxide nanoparticles (1/10 LD 50) in 1ml of 5% gum acacia solution as a solvent once daily. Group IV: gavaged orally (100 mg/kg NAC then 1200 mg/kg TiO2 NPs once daily. After 6 weeks rats from each group and subgroup were subjected the following biochemical parameters: Tumor necrosis factor alpha and CBC with differential count. The rats were sacrificed and spleen was dissected and subjected to histopathological examination. Cell suspension from the spleen was examined to determine the extent of DNA damage through DNA extraction and gel electrophoresis. Conclusion: TiO2 NPs induced time dependent toxic effects and DNA damage in the spleen and administration of NAC with TiO2 NPs offers protection against their damaging effect. Recommendation:it is recommended to increase public awareness about health impact of TiO 2 nanoparticles through nonessential drug additives, food colors, toothpastes etc.to limit their ingestion.
Background: Acrylamide (ACR) is an industrial pollutant, an exposure to acrylamide via different routes causes selective neurotoxicity. Aim of the Work: This work was performed to study potential neurotoxic effects of acrylamide on the cerebellum in adult albino rats by evaluation of neurobehavioral functional observational tests (gait score, landing hind limb foot splay), histopathological and immunhistochemichal testing of cerebellum. Materials and Methods:This study was carried out on 48 adult male albino rats which divided into 4 equal groups; GroupI (negative control group), Group II (positive control group) GroupIII (low dose acrylamide): Subdivided into two equal subgroups( III a& IIIb ) : each rat was gavaged orally with daily dose of 8.5mg/kg acrylamide for 4 & 8 weeks respectively. Group IV (high dose acrylamide): Subdivided into two equal subgroups( IV a& IV b ) : each rat was gavaged orally with daily dose of 17 mg/kg acrylamide for 4 & 8 weeks respectively. Results: There was a significant increase in both mean rank and mean values of gait scores and landing hind limb foot splay of both treated groups as compared to those of control groups. There was a strong positive correlation between foot splay and gait score, Microscopic examination of H&E stained of cerebellum of both treated groups showed loss of purkinjie cells, ACR affections were dose and time dependent . Silver stained cerebellar sections of rats received low dose for 4 weeks showed loss of some Purkinje cells, other rats received low dose for 8 weeks or high dose showed loss of most Purkinjie cells and the fibers of the white matter were seen with progressive fragmentation. Immunolocalization of Glial Fibrillary Acidic Protein (GFAP) in the cerebellum of treated groups showed progressive distribution of GFAP-positive astrocytes which was dose and time dependent. There was a strong positive correlation between area percentage and landing hind limb foot splay, a moderate positive correlation between area percentage and gait score. Conclusion: Acrylamide has a neurotoxic effect clarified by impairment of gait score and increase in landing hind limb foot splay. The abnormal neurobehavioral functional observational tests were associated to cerebellar histopathological changes in the form of selective loss of purkinjie cell, axonapathy and gliosis. Recommendation: it is recommended to increase public awareness about the health impact of exposure to acrylamide.
Background: Postmortem redistribution (PMR) is the changes that occur in drug concentrations after death. Lidocaine is the most popular local anesthetic used worldwide and midazolam is a widely used pre-anesthetic anxiolytic and sedative. Aim of the Work: This work was performed to study potential early phase postmortem redistribution of lidocaine and midazolam, as well as, the influence of storage temperature on it in adult albino rats. This was done by measuring their concentrations in blood (cardiac blood and external iliac vein blood) and tissues (heart, lungs and liver). Calculation of cardiac blood to peripheral blood ratio (C/P) and Liver to peripheral blood ratio (L/P) was performed. Materials and Methods: This study was carried out on 36 adult male albino rats which divided into two main groups (18 rats each). Group I (Lidocaine): Rats received a single SC injection of 2% lidocaine HCL (67 mg/kg), and sacrificed 30 minutes later. This group was subdivided into three equal groups; AM control (L-AM), 15 minutes PM at 4ºC (L-PM4) and 15 minutes PM at 21ºC (L-PM21). Group II (Midazolam): Rats received single IV injection of midazolam (75 mg/kg), and sacrificed 30 minutes later. This group was subdivided into three equal groups; AM control (M-AM), 15 minutes PM at 4ºC (M-PM4), 15 minutes PM at 21ºC (M-PM21). Results: There were significant changes in lidocaine and midazolam concentrations in both tissues and blood samples as compared to those of corresponding AM control groups. Markers of PMR revealed early phase PMR of lidocaine by L/P ratios > 20 at 21 ºC. Storage temperature at 4ºC arrested lidocaine PMR as recorded by both C/P ratios < 1 and L/P ratios < 5. Midazolam was prone to postmortem degradation that interfered with PMR assessment. Midazolam revealed minimal early phase postmortem redistribution as demonstrated by C/P ratios just above 1 at 4 ºC. L/P ratio was a more reliable marker for PMR than C/P ratio. Conclusion: Lidocaine was highly liable to undergo early phase PMR as demonstrated by L/P ratios above 20 at 21 ºC. However, storage at 4ºC retarded lidocaine PMR. Midazolam was subjected to postmortem degradation and had minimal early phase PMR as demonstrated by C/P ratios just above 1 at 4 ºC. Recommendation: it is recommended to increase forensic toxicologists' awareness about PMR of lidocaine and midazolam, and their influence on the interpretation of PM toxicological analysis.
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