The possible counteractive effect of gold nanoparticles against streptozotocin-induced type 1 diabetes in young male albino rats.

The current study was performed to study the effect of biologically synthesised gold nanoparticles (AuNPs) to control hyperglycaemic conditions in streptozotocin (STZ)-induced diabetic mice. In this study, the rats were divided into four groups: Group I normal control rats (non-diabetic, untreated); Group II diabetes-induced rats used as diabetic controls DC (diabetic, untreated). Group III diabetes-induced rats treated with AuNPs DT; Group IV normal rats treated with AuNPs NT. Diabetes was induced by administering an intraperitoneal injection of a freshly prepared solution of STZ (50mg/kg body weight (bw)). The glucose level was significantly increased in the diabetic control rats compared with the controls (P<0.001). Decreased liver function and kidney function were detected in the diabetic treated rats and normal treated rats after AuNP administration compared with the controls. The present study is the first to demonstrate that AuNPs significantly enhance antioxidant production in STZ-induced diabetic rats, a recognised model of type 1 diabetes mellitus (T1DM).

Pancreatic response to gold nanoparticles includes decrease of oxidative stress and inflammation in autistic diabetic model.

BACKGROUND: Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt. RESULTS: At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P < 0.05). Oxidised glutathione levels were lower (P > 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. CONCLUSIONS: Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs.

Evaluation of the possible protective role of quercetin on letrozole-induced testicular injury in male albino rats.

BACKGROUND: The purpose of this study was to appraise the possible adverse effects of quercetin against the aromatase inhibitor letrozole-induced developmental toxicity potential in male Wistar rats. METHODS: Control male albino rats were received vehicles used for flavonoids and vehicle used for letrozole. The rats in the first experimental group received letrozole at 0.04 mg/kg body weight (bwt) for 3 months. The second experimental group was treated with the flavonoid quercetin by gavage at a dose of 50 mg/kg bwt for 10 consecutive days after letrozole administration. RESULTS: Major treatment-related effects of letrozole included a dose-dependent increase in hormone levels and lipid peroxidation following exposure to 0. 04 mg/kg letrozole; and severe abnormalities with severe cellular deformation and disorganization in both spermatogenic and interstitial cells. The seminiferous tubules of the testes of the animals given quercetin and letrozole exhibited a rather normal appearance and the measured hormone levels were restored to nearly the normal levels. CONCLUSION: Exposure doses of letrozole that are equal to the daily recommended human dose has toxic effects on the spermatogenic lineage in rats, while simultaneous treatment of quercetin and letrozole could prevent the deleterious effects on testicular tissue caused by letrozole administration.

The role of apitoxin in alleviating propionic acid-induced neurobehavioral impairments in rat pups: The expression pattern of Reelin gene.

The efficacy of apitoxin (bee venom; BV) in ameliorating propionic acid (PPA) -induced neurobehavioral impacts was studied. Sixty rat pups were enrolled in a split litter design to six groups: a control group, a PPA-treated group, a BV-treated group, a BV/PPA protective group, a PPA/BV therapeutic group, and a BV/PPA/BV protective and therapeutic group. Exploratory, social, locomotor, and repetitive/stereotype-like activities were assessed and prosocial, empathy, and acquired behavior were evaluated. Levels of neurotransmitter including serotonin, dopamine, and gamma-aminobutyric acid (GABA) were determined and a quantitative analysis of Reelin gene expression was performed. PPA treatment induced several behavioral alterations, as reduced exploratory activity and social behaviors, increased repetitive/stereotypic behaviors, and hyperactivity. In addition, a marked decline of neurotransmitters and down-regulation of Reelin mRNA expression were observed. BV exhibited high efficiency in ameliorating the PPA-induced neurobehavioral alterations, particularly when applied both before and after PPA administration. Overall, the results implied that BV has merit as a candidate therapeutic treatment to alleviate PPA-induced neurobehavioral disorders.

Apitoxin protects rat pups brain from propionic acid-induced oxidative stress: The expression pattern of Bcl-2 and Caspase-3 apoptotic genes.

The primary aim of this study was to determine the potential modulatory role of the apitoxin (bee venom; BV) against propionic acid (PPA)-induced neurotoxicity. The biochemical responses to PPA exposure in rat pups were assayed, including changes in the antioxidant barrier systems and lipid peroxidation and protein oxidation biomarkers in the brain tissue. DNA damage was measured by single-cell gel electrophoresis and differences in Bcl-2 and Caspase-3 mRNA expression were assessed using real-time PCR. Changes in amygdala complex ultrastructure were visually assessed using electron microscopy. Sixty rat pups were assigned into six groups: a control group, a PPA-treated group, a BV-treated group, a protective co-treated group, a therapeutic co-treated group, and a protective/therapeutic co-treated group. The results indicate that PPA induced a pronounced increase (64.6%) in malondialdehyde (MDA), and in DNA damage (73.3%) with three-fold increase in protein carbonyl concentration. A significant reduction was observed in the enzyme activities of superoxide dismutase (SOD) (48.7%) and catalase (CAT) (74.8%) and reduced glutathione (GSH) level (52.6%). BV significantly neutralized the PPA-induced oxidative stress effects, especially in the BV protective/therapeutic co-treated group. In this group, GSH levels were restored to 64.5%, and MDA, protein carbonyl levels and tail moment % were diminished by 69.5, 21.1 and 18.8% relative to the control, respectively. Furthermore, while PPA induced significant apoptotic neural cell death, BV markedly inhibited apoptosis by promoting Bcl-2 expression and blocking Caspase-3 expression. BV markedly restored the normal ultrastructural morphology of the amygdala complex neurons. These results conclusively demonstrate that BV administration provides both protective and therapeutic effects in response to the PPA-induced deleterious effects, including oxidative stress, DNA damage, and neuronal death in the brains of rat pups.

Possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats.

AIM: To examine the possible ameliorative effect of breastfeeding and the uptake of human colostrum against coeliac disease in autistic rats. METHODS: Female rats were fed a standard diet and received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception. In study 1, neonatal rats were randomly subjected to blood tests to investigate autism. In study 2, the 1(st) group was fed by the mother after an injection of interferon-γ (IFN-γ) and administration of gliadin. The pups in the 2(nd) group were prevented from accessing maternal milk, injected IFN-γ, administered gliadin, and hand-fed human colostrum. The normal littermates fed by the table mothers were injected with physiological saline and served as normal controls in this study. RESULTS: The protein concentration was higher in group 2 than in group 1 in the duodenum (161.6 ± 9 and 135.4 ± 7 mg/g of tissue, respectively, P < 0.01). A significant increase (P < 0.001) in body weight was detected in human colostrum-treated pups on post natal day (PND) 7 and 21 vs suckling pups in group 1. A delay in eye opening was noticed in the treated rats in group 1 on PND 13 compared with the control group and group 2. Administration of a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception resulted in significantly reduced calcium and vitamin D levels in study 1 compared with the control groups (P < 0.001). However, human colostrum uptake inhibited increases in the level of transglutaminase antibody in autistic pups with coeliac disease. CONCLUSION: The effects of early-life nutrition and human colostrum on the functional maturation of the duodenal villi in autistic rats with coeliac disease that might limit or prevent the coeliac risk with autism.

Gold nanoparticles induce apoptosis in MCF-7 human breast cancer cells.

BACKGROUND: Gold nanoparticles have recently been investigated with respect to biocompatibility according to their interactions with cells. The purpose of this study was to examine cytotoxicity and apoptosis induction by well-characterized gold nanoparticles in human breast epithelial MCF-7 cells. METHODS: Apoptosis was assessed by TUNEL, cytotoxicity by MTT assay and caspase 3, 9, p53, Bax and Bcl expression by real-time PCR assays. RESULTS: Gold nanoparticles at up to 200 µg/mL for 24 hours exerted concentration-dependent cytotoxicity and significant upregulation of mRNA expression of p53, bax, caspase-3 and caspase-9, whereas expression of anti- apoptotic bcl-2 was down-regulated. CONCLUSION: To the best of our knowledge this is the first report showing that gold nanoparticles induce apoptosis in MCF-7 cells via p53, bax/bcl-2 and caspase pathways.

The protection role of heat shock protein 70 (HSP-70) in the testes of cadmium-exposed rats.

Cadmium (Cd) is an environmental carcinogenic pollutant known to inactivate several proteins involved in DNA repair systems while at the same time creating an oxidative stress that can result in additional DNA lesions. The testis and the lung are the target organs for cadmium carcinogenesis. Increased production of oxidants in vivo can cause damage to intracellular macromolecules such as DNA, proteins and lipids, which in turn lead to oxidative injury. So, this investigation aimed to evaluate the protective role of L-Carnitine through up regulation of HSPs against DNA damage induced by cadmium chloride. The current study was carried out on forty adult male rats, each with average weight 220-250g., were divided into 4 equal groups. 1(st) group was received saline solution (0.5 ml/100 g body weight) and kept as control. 2(nd) group was received 500mg / kg body weight L-Carnitine intraperitoneally (IP). 3(rd) group was administered 1.2 mg cadmium chloride IP. 4(th) group was received both cadmium chloride and L-Carnitine simultaneously. The comet assay parameters showed significantly increased HSP70 and DNA damage in testis cells after 10 and 56 days in the third group. Meanwhile, HSP70 showed significantly decreased levels after 10 days and 56 days in the fourth group after L-Carnitine treatment simultaneously with cadmium chloride. The results of the present study demonstrate a damaging effect of cadmium chloride on DNA of the testis cells (with low stress response). This damaging effect increases the synthesis of HSP70 that upregulated by L-Carnitine treatment and showed ameliorative effect of the cells for recovery.