The Prophylactic Effect of Vitamin C and Vitamin B12 against Ultraviolet-C-Induced Hepatotoxicity in Male Rats.

Ultraviolet C (UVC) devices are an effective means of disinfecting surfaces and protecting medical tools against various microbes, including coronavirus. Overexposure to UVC can induce oxidative stress, damage the genetic material, and harm biological systems. This study investigated the prophylactic efficacy of vitamin C and B12 against hepatotoxicity in UVC-intoxicated rats. Rats were irradiated with UVC (725.76, 967.68, and 1048.36 J/cm2) for 2 weeks. The rats were pretreated with the aforementioned antioxidants for two months before UVC irradiation. The prophylactic effect of vitamins against UVC hepatotoxicity was evaluated by monitoring the alteration of liver enzyme activities, antioxidant status, apoptotic and inflammatory markers, DNA fragmentation, and histological and ultrastructural alterations. Rats exposed to UVC showed a significant increase in liver enzymes, oxidant-antioxidant balance disruption, and increased hepatic inflammatory markers (TNF-α, IL-1ß, iNOS, and IDO-1). Additionally, obvious over-expression of activated caspase-3 protein and DNA fragmentation were detected. Histological and ultrastructural examinations verified the biochemical findings. Co-treatment with vitamins ameliorated the deviated parameters to variable degrees. In conclusion, vitamin C could alleviate UVC-induced hepatotoxicity more than vitamin B12 by diminishing oxidative stress, inflammation, and DNA damage. This study could provide a reference for the clinical practice of vitamin C and B12 as radioprotective for workers in UVC disinfectant areas.

Biochemical, Histological, and Ultrastructural Studies of the Protective Role of Vitamin E on Cyclophosphamide-Induced Cardiotoxicity in Male Rats.

BACKGROUND: Cyclophosphamide (CP) (Cytoxan or Endoxan) is an efficient anti-tumor agent, widely used for the treatment of various neoplastic diseases. The study aimed to investigate the protective role of vitamin E (vit E) in improving cardiotoxicity in rats induced by CP. MATERIALS AND METHODS: Forty male Wistar rats were divided randomly into four experimental groups (each consisting of ten rats); the control group was treated with saline. The other three groups were treated with vit E, CP, and the combination of vit E and CP. Serum lipid profiles, enzyme cardiac biomarkers, and cardiac tissue antioxidants were evaluated, as well as histological and ultrastructure investigations. RESULTS: CP-treated rats showed a significant increase in serum levels of cardiac markers (troponin, CK, LDH, AST, and ALT), lipid profiles, a reduction in the antioxidant enzyme activities (CAT, SOD, and GPx), and an elevation in the level of lipid peroxidation (LPO). The increase in the levels of troponin, LDH, AST, ALP, and triglycerides is a predominant indicator of cardiac damage due to the toxic effect of CP. The biochemical changes parallel cardiac injuries such as myocardial infarction, myocarditis, and heart failure. Vitamin E played a pivotal role, as it attenuated most of these changes because of its ability to scavenge free radicals and reduce LPO. In addition, vit E was found to improve the histopathological alterations caused by CP where no evidence of damage was observed in the cardiac architecture, and the cardiac fibers had regained their normal structure with minimal hemorrhage. CONCLUSIONS: As a result of its antioxidant activity and its stabilizing impact on the cardiomyocyte membranes, vit E is recommended as a potential candidate in decreasing the damaging effects of CP.

Effect of Saffron Extract on the Hepatotoxicity Induced by Copper Nanoparticles in Male Mice.

BACKGROUND: Nanotechnology application has widespread use in many products. Copper nanoparticles (CuNPs) are widely used in industrial applications. The present study was conducted to investigate the effect of the ethanolic saffron extract (ESE) as a natural antioxidant on the hepatotoxicity induced by CuNPs in male mice. METHODS: The characterization of CuNPs was determined using ultraviolet-visible absorption spectroscopy, particle size analysis, zeta potential, Fourier-transform infrared spectroscopy, and electron microscope. The effect of saffron on the hepatotoxicity induced by CuNPs in mice was evaluated by evaluating the survival rate of the mice, oxidative stress, antioxidant capacity, DNA evaluation, as well as its effect on the histology and transmission electron microscope of the liver. RESULTS: The results revealed that all parameters were affected in a dose-dependent manner by CuNPs. These effects have been improved when the treatment of CuNPs is combined with ethanolic saffron extract. CONCLUSIONS: We can conclude that saffron and its bioactive crocin portion can prevent CuNP-induced oxidative liver damage. This substance should be useful as a new pharmacological tool for oxidative stress prevention.

Disruption of brain conductivity and permittivity and neurotransmitters induced by citrate-coated silver nanoparticles in male rats.

As one of the most exonerative, competitive, and abundant nanoparticles in curative uses, silver nanoparticles (AgNPs) play a growing important role in developing global neurodegeneration. Herein, we inspected the neurotoxic and histopathological effects of the oral dose of 26.9 nm citrate-coated AgNPs (100 and 1000 mg/kgbw, 28 days) on the brain conductivity and permittivity combined with neurotransmitter assays. While male mice in the control group were given deionized water. In terms of biophysical levels, the brain electric conductivity and relative permittivity were significantly decreased in the 26.9 nm citrate-coated AgNP treated groups versus the controls. Besides, 26.9 nm citrate-coated AgNP treatment resulted in a significant deficiency in the concentrations of brain acetylcholine esterase, dopamine, and serotonin. Total brain contents of silver ion significantly increased in a dose-dependent manner. Further, light and electron microscopy revealed a progressive disruption in the lamellar pattern of the myelinated axons of the nerve fibers, in addition to the accumulation of nanosilver in lysosomes and swollen mitochondria in axoplasm. In conclusion, 26.9 nm citrate-coated AgNPs are capable of gaining access to the brain of mice and causing electric conductivity and relative permittivity damage along with a high degree of cellular toxicity in the brain tissue. Therefore, the present study highlights, for the first time, the adverse effects of the citrate-coated AgNPs to the brain of mice and raises the concern of their probable neurotoxic impacts which is helpful for conclusive interpretation of future behavioral and potential neurodegeneration-based aspects. It would be of interest to investigate citrate-coated AgNPs mediated axonal relevant-signal transduction levels in future studies.

Effects of lithium on cytokine neuro-inflammatory mediators, Wnt/ß-catenin signaling and microglial activation in the hippocampus of chronic mild stress-exposed rats.

Microglial in vivo production of pro-inflammatory cytokines is central to the pathogenesis of multiple neurological disorders including depression, with a rising role of Wnt/ß-catenin signaling as potential regulator of microglia-mediated neuro-inflammation. This study aimed at investigating the hippocampal expression of the Wnt/ß-catenin pathway in chronic mild stress (CMS)-exposed rats and the effects of Lithium (Li) on the expression of this pathway as a method to identify a plausible link between exposure to chronic stress, microglial activation, and neuroinflammation. METHODS: The effect of chronic administration of Li was investigated on behavioral changes, hippocampal expression of Wnt-DVL-GSK3ß-ß-catenin signaling pathway, and microglial activation in CMS-exposed male Wistar rats RESULTS: CMS induced a depressive-like behavior associated with increased pro-inflammatory microglial activation and reduced hippocampal expression of the Wnt/ß-catenin signaling pathway. Chronic Li treatment ameliorated stress induced-behavioral changes, reduced microglial activation and enhanced the hippocampal expression of Wnt/ß-catenin signaling pathway. CONCLUSION: This work highlights that Li-induced inhibition of GSK-3ß with subsequent accumulation of ß-catenin could impede pro-inflammatory microglia activation which is a key pathological hallmark associated with depression. Wnt/ß-catenin signaling represents a promising therapeutic target, not only for alleviation of depression, but also for a wide array of neurological disorders.

Ginger causes subfertility and abortifacient in mice by targeting both estrous cycle and blastocyst implantation without teratogenesis.

BACKGROUND: Due to renowned medicinal properties, Ginger rhizomes (Zingiber officinale Roscoe) used traditionally in the treatment of arthritis, rheumatism, muscular aches, constipation, indigestion, hypertension, dementia, fever, and infectious diseases. As an antiemetic, Ginger is consumed by approximately 80% of pregnant women to treat nausea and vomiting of early pregnancy. PURPOSE: The aim of this study is to evaluate the impact of ginger extract on the oestrous cycle and implantation in female mice. STUDY DESIGN AND METHODS: Four experimental episodes were identified. One considered the main study of outcomes and lasted 90 days; one lasted 35 days and considered the oestrous cycle; while the third and fourth intended antifertility and abortifacient and continued 20 days for each. Mice dosed Ginger orally at 0, 250, 500, 1000 or 2000  mg/kgbw/day (GNC, GN1, GN2, GN3, GN4, respectively). RESULTS: GN3 and GN4 dams showed maternal toxicity. High dose significantly reduced the number of live fetuses and increased fetal death and resorption. Mice treated with 2000  mg/kgbw/day displayed significant decreases in implantation sites. At a dose of 2000  mg/kgbw/day, Ginger prolonged the length of oestrous cycle with a significant decrease in the duration of diestrous-metestrus (luteal) phase, prolonged proestrus-estrus (ovulatory) phase and reduced the number of cycles as well. Therefore, Ginger impairs the normal growth of corpus luteum because of progesterone insufficiency during early pregnancy. The observed-adverse-effect dose set at 2000  mg/kgbw, but no-observed-adverse-effect dose set at 250 and 500  mg/kgbw. CONCLUSION: These findings suggest that Ginger can disrupt the oestrous cycle and blastocyst implantation without teratogenesis.

Effect of cryotherapy on pain management at the puncture site of arteriovenous fistula among children undergoing hemodialysis.

OBJECTIVE: To evaluate the effectiveness of cryotherapy in managing the pain at the puncture site of Arterio-Venous Fistula (AVF) among children undergoing maintenance hemodialysis (HD). METHODS: A one-group pre-post quasi-experiment was performed in two HD centers affiliated with Cairo University. The experiment involved 40 children with AVF undergoing HD. Before puncturing, cryotherapy was applied using 2 cm-3 cm pieces of frozen distilled water in a plastic bag. Pain was assessed subjectively and objectively in two dialysis sessions before and after cryotherapy. A part from a physiological assessment of vital signs, pain was assessed using the Wong-Baker Faces Pain and the Observed Pain Behavior rating scales. All research ethics were applied. RESULTS: HD had a median duration of four years, while cryotherapy had a median application time of 8.8 min. The Wong-Baker Faces Pain score and almost all observed pain behaviors significantly decreased after cryotherapy. Significant improvements were observed in respiratory rate before and after needle puncture and in oxygen saturation after needle puncture. A lower skin dryness was observed after cryotherapy (12.5%) than before cryotherapy (52.5%; p < 0.001). CONCLUSIONS: Cryotherapy can effectively reduce the venipuncture pain among children with AVF undergoing maintenance HD. However, the confounding effects of distraction and the non-randomized design used must be both considered when interpreting the findings. This study recommends the use of cryotherapy in managing needle puncture pain. Further research must adopt a randomized trial design with a placebo to support further the benefits of this procedure.

Bactericidal application and cytotoxic activity of biosynthesized silver nanoparticles with an extract of the red seaweed Pterocladiella capillacea on the HepG2 cell line.

BACKGROUND: Nano-biotechnology is recognized as offering revolutionary changes in various fields of medicine. Biologically synthesized silver nanoparticles have a wide range of applications. MATERIALS AND METHODS: Silver nanoparticles (AgNPs) were biosynthesized with an aqueous extract of Pterocladiella (Pterocladia) capillacea, used as a reducing and stabilizing agent, and characterized using UV-VIS spectroscopy, Fourier Transform Infra red (FT-IR) spectroscopy, transmission electron microscopy (TEM) and energy dispersive analysis (EDX). The biosynthesized AgNPs were tested for cytotoxic activity in a human hepatocellular carcinoma (HepG2) cell line cultured in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum, 1% antibiotic and antimycotic solution and 2 mM glutamine. Bacterial susceptibility to AgNPs was assessed with Staphylococcus aureus, Bacillus subtilis [Gram+ve] and Pseudomonas aeruginosa and Escherichia coli [Gram-ve]. The agar well diffusion technique was adopted to evaluate the bactericidal activity of the biosynthesized AgNPs using Ampicillin and Gentamicin as gram+ve and gram-ve antibacterial standard drugs, respectively. RESULTS: The biosynthesized AgNPs were 11.4±3.52 nm in diameter. FT-IR analysis showed that carbonyl groups from the amino acid residues and proteins could assist in formation and stabilization of AgNPs. The AgNPs showed potent cytotoxic activity against the human hepatocellular carcinoma (HepG2) cell line at higher concentrations. The results also showed that the biosynthesized AgNPs inhibited the entire panel of tested bacteria with a marked specificity towards Bacillus subtillus. CONCLUSIONS: Cytotoxic activity of the biosynthesized AgNPs may be due to the presence of alkaloids present in the algal extract. Our AgNPs appear more bactericidal against gram-positive bacteria (B. subtillus).

Kidney antioxidant status, biochemical parameters and histopathological changes induced by methomyl in CD-1 mice.

The widespread of pesticide in public health and agriculture has caused severe environmental pollution and health hazards. Methomyl is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. In this study, we aimed to investigate the effects of methomyl at different time intervals on lipid peroxidation, reduced glutathione (GSH), total sulfhydryl group (T-SH), antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and histopathological changes in mice kidney. Ten CD-1 mice per group were assigned to one of four treatment groups. Group one served as control while groups 2, 3 and 4 were orally treated with 1mgmethomyl/kg BW for 10, 20 and 30 days, respectively. Methomyl significantly increased lipid peroxidation in kidney as compared to control group. Levels of GSH and T-SH and activities of SOD, CAT and GST were found to be decreased. On the other hand, methomyl significantly increased the levels of urea, uric acid and creatinine in serum. The histological examination of kidney revealed damage involving the entire renal nephrons in both 20 and 30 days of methomyl exposure. Severe dilatation of the cortical tissue, congested glomerulus with swelling of the endothelial cells and degeneration of the epithelium cells lining the tubules were observed. In conclusion, the results suggest that methomyl exposure can cause renal damage, oxidative stress, perturbations in antioxidant defense system and histopathologic changes in mice kidney in a time dependent manner.

Efficacy of Ginkgo biloba on vaginal estrous and ovarian histological alterations for evaluating anti-implantation and abortifacient potentials in albino female mice.

Ginkgo extract, EGb 761 is known as a vasoregulatory variable for the conventional reproduction therapy. EGb 761 was orally administered in 0 (control), 3.7, 7.4, and 14.8 mg/kg bw/day for 28 days (thereafter mated with normal fertile male), from day 1 to day 7 of pregnancy or from the 10th to 18th day of pregnancy, respectively. Vaginal smears were performed daily. On 20th day of pregnancy, the females were killed by cervical dislocation and their kidneys, liver, brain, placenta, spleen and ovaries were removed and weighed. The ovaries were prepared for histological examinations, and then ovarian follicles were counted. Maternal toxicity, estrous cycle, reproductive hormones, ovarian follicle counts, resorption index, implantation index, fetal viability and fetuses, and placenta mean weights were evaluated. There was a dose-dependent ovarian toxic effect of EGb 761. Ovarian follicle counts, resorption index, implantation index, fetal viability were significantly reduced in 14.8 mg/kg bw/day dose. Treatment with 14.8 mg/kg bw/day EGb 761 induced disruption of estrous cycle and caused maternal toxicity, in addition to fetal toxicity. Therefore, the data obtained indicate that Ginkgo biloba extract at 14.8 mg/kg bw/day dose level exhibit toxic effect on reproductive cyclicity and could have anti-implantation and abotifacient properties in female mice.

Biochemical and histopathological changes induced by different time intervals of methomyl treatment in mice liver.

The present study was designed to evaluate the toxic effects induced by different time intervals of methomyl exposure on liver antioxidant defense system, oxidative stress, liver function biomarkers and histopathology in CD-1 mice. Ten male mice per group were assigned to one of four treatment groups. Group one served as control while group 2, 3 and 4 were orally treated with one mg methomyl/kg BW for 10, 20 and 30 days, respectively. Results obtained showed that methomyl significantly induced TBARS and decreased the activity of antioxidant enzymes, glutathione S-transferase, superoxide dismutase and catalase and the levels of reduced glutathione in mice liver. Aminotransferases and alkaline phosphatase activities were significantly decreased in liver due to methomyl administration, while the activities of these enzymes were significantly increased in serum. In addition, liver lactate dehydrogenase activity was significantly increased. On the contrary, methomyl treatment caused a significant decrease in liver acid phosphatase. The histology of mice liver treated with methomyl for 10, 20 and 30 days of duration showed dilation of central vein, sinusoids between hypertrophied hepatocytes and nuclear degeneration with mononuclear cell infiltration. In conclusion, exposure to methomyl induced toxicity and oxidative stress in mice liver via free radicals mechanism. Also, methomyl might have affected cell metabolism, cell membrane permeability and the detoxification system in liver.

Endocrine-disrupting and cytotoxic potential of anticholinesterase insecticide, diazinon in reproductive toxicity of male mice.

We evaluated the effects of diazinon (2, 4.1 and 8.2mg/kg bw/day for 4 weeks) in gonadotropins, testosterone and estrogen levels, whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by acetylcholinesterase inhibition and histopathological changes in adult mice testes. Diazinon at doses higher than 2mg/kg bw/day resulted in decreased testis weight, inhibition in acetylcholinesterase activities, decrease in levels of luteinizing hormone and follicle stimulating hormone, following reduction in mating and fertility indices. Diazinon increased testosterone content in 4.1mg/kg group, but decreased testosterone concentration in 8.2mg/kg group. Diazinon increased estrogen, prolactine and decreased levels of acetylcholinesterase activities in 4.1mg/kg group but levels of luteinizing hormone and follicle stimulating hormone remained unmodified. It may be simply postulated a scenario that acetylcholine in the cholinergic neurons has a potential threshold to perform a crucial part in the complex circuitry of neuroendocrine regulatory mechanisms. On overaccumulation, other neurotransmitters can be appropriately recruited to modulate the mechanisms of circuitry.

Evaluation of developmental toxicity induced by anticholinesterase insecticide, diazinon in female rats.

Developmental toxicities, including birth defects, are significant public health problems. This study was planned to assess the cholinergic and developmental potentials of diazinon that is widely used as an organophosphate insecticide. Pregnant female Sprague-Dawley rats were given diazinon orally at doses of 0, 1.9, 3.8, and 7.6 mg/kg body weight (b.w.)/day on gestation days 6 to 15. Maternal brain acetylcholinesterase activities, measured on gestation day20, were significantly decreased at 3.8 and 7.6 mg/kg b.w./day, but fetal acetylcholinesterase activity was not altered. Maternal toxicities, as evidenced by cholinergic symptoms including diarrhea, tremors, weakness, salivation, and decreased activities, were observed at the 3.8 and 7.6 mg/kg b.w./day dose groups. Net gravid uterine weight was decreased at a dose of 7.6 mg/kg b.w./day. No maternal effects were apparent in the 1.9 mg/kg b.w./day dose group. Maternal toxicity at a dose of 3.8 mg/kg b.w./day did not induce fetotoxicity or teratogeneicity. However, 7.6 mg/kg b.w./day doses significantly resulted in fetal toxicity and malformations in addition to maternal toxicity in animals. In conclusion, teratogenic disorders only outlined by doses that produced marked maternal toxicity. Since the malformations were not morphologically related, they were considered to be secondary to maternal toxicity; hence, the malformations were not related to cholinesterase inhibition.

Histological and electron microscopic studies of the effect of beta-carotene on the pancreas of streptozotocin (STZ)-induced diabetic rats.

To evaluate the protective effect of beta-carotene on induction of diabetes by streptozotocin (STZ), 45 albino rats, weighed about 110-130 g were used. They were divided randomly into six groups. GI rats used as control; GII rats were injected i.p. with a single dose of 40 mg streptozotocin (STZ) to become diabetic; GIII and GIV, the diabetic rats were injected i.p. with 0.3 and 0.1 mg beta-carotene, respectively; GV and GVI rats were injected i.p. only with 0.3 and 0.1 mg beta-carotene respectively. At the end of the experiment, the final body weights, blood glucose and insulin levels were determined and the values were statistically analyzed. Histological, semithin and ultrathin sections were prepared for pancreatic tissues. In the diabetic rats (GII), there was significant loss in body weight accompanied by significant increase in blood glucose levels. In addition, many light and electron microscopic changes were observed in the acinar and endocrine beta-cells of islets of pancreas. These changes were summarized as disturbance of acini arrangement, shrinkage and pyknotic nuclei, vacuolation and dissolution of mitochondria and Golgi elements, degranulation of beta-cells. In addition to the significant decrease in blood glucose levels, 0.3 mg beta-carotene (Gill) had decreased most of these changes than 0.1 mg of it (GIV). So, GIII provides more protection for the pancreatic tissue more than GIV. Also, the results revealed that injection of rats only with 0.3 and 0.1 mg beta-carotene (GV and GVI) had no observable changes in the pancreatic tissues, except that there was an increase in number of the vacuolized mitochondria in most acinar and beta-cells of islets. In conclusions, 0.3 mg beta-carotene could normalize the biochemical disorders of diabetes and provides more protection for the pancreatic tissues than 0.1 mg from the damaging effect of STZ to a greater extent.

Analysis of CBP (CREBBP) gene deletions in Rubinstein-Taybi syndrome patients using real-time quantitative PCR.

Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome characterized by facial abnormalities, broad thumbs, broad big toes, and growth and mental retardation as the main clinical features. RTS was shown to be associated with disruption of the CREB-binding protein gene CBP (CREBBP), either by gross chromosomal rearrangements or by point mutations. Translocations and inversions involving chromosome band 16p13.3 form the minority of CBP mutations, whereas microdeletions occur more frequently (about 10%). Most deletion studies in RTS are performed by FISH analysis, and five cosmids must be used to cover the whole of the CBP gene, which spreads over 150 kb. Here we report the design of gene dosage assays by real-time quantitative PCR that are targeted on three exons located respectively at the 5' end (exon 2), in the middle (exon 12), and at the 3' end (exon 30) of the CBP gene. This technique proved to be efficient and powerful in finding deletions and complementary to the other available techniques, since it allowed us to identify deletions at the 3' end of the gene that had been missed by FISH analysis, and to refine some deletion breakpoints. Our results therefore suggest that real-time quantitative PCR is a useful technique to be included in the deletion search in RTS patients.