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Increasing attention has been paid in the past decade to assessing the toxicological effects of nanoparticles and finding a protectant; thus, the current study aimed to investigate the protective effect of the mitochondria-targeting drug methylene blue (MB) against copper oxide nanoparticle (CuO-NP)-induced neurobehavioral toxicity in rats. For this purpose, twenty rats were allocated to four equal groups (n = 5). The negative control group received distilled water intraperitoneally (IP) and Tween 80 (10 %) orally. The CuO-NP group was given a dose of 100 mg/kg of CuO-NPs, administered orally, and the positive control group was treated with 1 mg/kg MB intraperitoneally (IP). The final group was concurrently exposed to CuO-NPs and MB for 14 consecutive days. At the end of the study, each group was neurobehaviorally blind tested relative to other experimental animals, then brain tissue markers were determined and a histopathological examination was conducted. The results showed that supplementation with CuO-NPs induced neurobehavioral alterations; increased Cu content in the brain; and enhanced lipid peroxidation (malondialdehyde [MDA]), protein peroxidation (protein carbonyl [PC]), and DNA oxidative damage (8-hydroxy-2-deoxyguanosine [8−OH-dG]) compared to other treatments. In addition, a decrease was noted in the mitochondrial dehydrogenases’ (aldehyde dehydrogenase 2 [ALDH2], and glutamate dehydrogenase [GDH]) activity in Cu-exposed rats. The histopathological findings revealed shrunken, pyknotic, and hypereosinophic cortical neurons and increased immune positive brown staining of caspase-3 protein, indicating apoptosis. Co-treatment with methylene blue ameliorated the neurotoxic effects of CuO-NPs; therefore, MB evidently had a powerful modulatory effect against the neurotoxicity of nano-Cu oxide via its antioxidant and mitochondrial protection properties.

Dietary intake of fructose corn syrup in sweetened beverages is associated with the development of metabolic syndrome and obesity. We hypothesized that inflammatory cytokines play a role in lipid storage and induction of liver injury. Therefore, this study intended to explore the expression of adipocytokines and its link to hepatic damage. Rats were assigned to drink water, cola soft drink (free access) and aspartame (240 mg/kg body weight/day orally) for 2 months. The lipid profiles, liver antioxidants and pathology, and mRNA expression of adipogenic cytokines were evaluated. Subchronic intake of soft drink or aspartame substantially induced hyperglycemia and hypertriacylglycerolemia, as represented by increased serum glucose, triacylglycerol, low-density lipoprotein and very low-density lipoprotein cholesterol, with obvious visceral fatty deposition. These metabolic syndromes were associated with the up-regulation of leptin and down-regulation of adiponectin and peroxisome proliferator activated receptor-γ (PPAR-γ) expression. Moreover, alterations in serum transaminases accompanied by hepatic oxidative stress involving induction of malondialdehyde and reduction of superoxide dismutase, catalase, and glutathione peroxidase and glutathione levels are indicative of oxidative hepatic damage. Several cytoarchitecture alterations were detected in the liver, including degeneration, infiltration, necrosis, and fibrosis, predominantly with aspartame. These data suggest that long-term intake of soft drink or aspartame-induced hepatic damage may be mediated by the induction of hyperglycemia, lipid accumulation, and oxidative stress with the involvement of adipocytokines.

This study was designed to investigate neuro-behavioral, neuro-biochemical and neuro-morphological alterations induced by sub-acute toxicity of lead (Pb) in male Wistar rats as well as the assessment of the neuroprotective effect of thiamine hydrochloride against Pb-induced behavioral, biochemical and morphological neuro-alterations. For this purpose 24 male Wistar rats were randomly divided into 4 groups (n=6). Rats in the 1st group were treated with lead acetate orally at dose of 100 mg/kg b.wt. Animals in 2nd group were received leaded water orally + 100 mg/kg thiamine hydrochloride intraperitoneally. 3rd group were treated only with thiamine hydrochloride. 4th group was served as the control animals. Animals were exposed to treatments once daily for 7 consecutive days. Behavioral alterations were assessed by applying neurological tests as elevated plus-maze and Morris water maze. The main neurotransmission systems as cholinergic, adrenergic, serotonergic and GAB Aergic were evaluated in brain tissue homogenate. Morphological alterations was assessed histopathologically. Results revealed that, Pb exposure caused spatial learning and memory impairment, as well as a significant increase in the content of acetylcholine, serotonin and norepinephrine while the activity of acetylcholinesterase and GABA content showed a significant decrease. Hemorrhage in brain, mild perivascular edema and perivascular cuffing were the main pb-induced morphological alterations. Simultaneous administration of thiamine markedly ameliorated Pb-induced neurotoxicity which was indicated by comparatively better behavioral performance, alleviation of the neurotransmitters disturbances and decreased the severity of histopathological lesions. In conclusion, thiamine has been found to be extremely significant in the fighting of Pb-induced neuro-manifestations.

Aims This study explored whether silver nanoparticles (AgNPs) can disrupt tight-junctions integrity resulted in blood-brain barrier dysfunction along with oxidative stress, pro-inflammation, and apoptosis induction. Additionally, neuroprotective activities of α-lipoic acid (LA) and Ginkgo biloba (GB) were investigated. Main methods Forty adults rats were enrolled into; Control, AgNPs (50 mg/kg), LA (100 mg/kg) + AgNPs, and GB (120 mg/kg) + AgNPs. After 30 days, neuronal changes were assessed biochemically and histopathologically. Brain tissues oxidative indices, mRNA expression of proinflammatory cytokines and tight-junction proteins and pro-apoptotic biomarker, caspase-3 were investigated. Key findings AgNPs exposure enhanced lipid peroxidation (+195%) along with declines in glutathione (−43%), glutathione peroxidase (−34%), glutathione S-transferase (−31%), catalase (−43%), and superoxide dismutase (−38%) activities in brain tissues. The apparent brain oxidative damage was associated with obvious neuronal dysfunction that was ascertained by neuropathological lesions. AgNPs lowered serum acetylcholine esterase, iron and copper levels, and increased creatine phosphokinase and creatine phosphokinase–brain type activities. Following AgNPs exposure, brain silver and iron contents were increased, but the copper level was decreased. AgNPs up-regulated TNF-α (6.5-fold) and IL-1β (8.9-fold) transcript levels, and simultaneously over-expressed the caspase-3 protein in cerebrum and cerebellum inducing cell apoptosis. Moreover, AgNPs down-regulated the transcript levels of tight-junction proteins; JP-1 (0.65-fold) and JAM-3(0.81-fold). Significance LA and relatively GB improved the serious effects of AgNPs on the blood-brain barrier function and tight-junction proteins through their antioxidants, anti-inflammatory, and anti-apoptotic efficacies. Co-treatment with LA or GB may be favorable in ameliorating the neurotoxic side effects of AgNPs.

The potential antifibrotic effects of melatonin against induced hepatic fibrosis were explored.Rats were allocated into four groups: placebo; thioacetamide (TAA) (200mg/kg bwt, i.p twice weekly for two months); melatonin (5mg/kgbwt, i.p daily for a week before TAA and continued for an additional two months); and melatonin plus TAA. Hepatic fibrotic changes were evaluated biochemically and histopathologically. Hepatic oxidative/antioxidative indices were assessed. The expression of hepatic proinflammatory cytokines (tumor necrosis factor-α, and interleukin-1β), fibrogenic-related genes (transforming growth factor-1β, collagen I, collagen, III, laminin, and autotaxin) and an antioxidant-related gene (thioredoxin-1) were detected by qRT-PCR.In fibrotic rats, melatonin lowered serum aspartate aminotransferase, alanine aminotransferase, and autotaxin activities, bilirubin, hepatic hydroxyproline and plasma ammonia levels. Melatonin displayed hepatoprotective and antifibrotic potential as indicated by mild hydropic degeneration of some hepatocytes and mild fibroplasia. In addition, TAA induced the depletion of glutathione, glutathione s-transferase, glutathione peroxidase, superoxide dismutase, catalase, and paraoxonase-1 (PON-1), while inducing the accumulation of malondialdehyde, protein carbonyl (C=O) and nitric oxide (NO), and DNA fragmentation. These effects were restored by melatonin pretreatment. Furthermore, melatonin markedly attenuated the expression of proinflammatory cytokines and fibrogenic genes via the upregulation of thioredoxin-1 mRNA transcripts.Melatonin exhibits potent anti-inflammatory, antioxidant and fibrosuppressive activities against TAA-induced hepatic fibrogenesis via the suppression of oxidative stress, DNA damage, proinflammatory cytokines and fibrogenic gene transcripts. In addition, we demonstrate that the antifibrotic activity of melatonin is mediated by the induction of thioredoxin-1 with attenuation of autotaxin expressions.

The morphopathological alterations of chronic cadmium (Cd) toxicity in Sarotherodon galilaeus were studied. 126 fish were used to determine 96 hrs LC50 of cadmium chloride, the obtained result was 28.3 mg/L. Forty-eight fish were used to induce chronic toxicity, twenty-four fish were exposed to 2.83 mg/L cadmium chloride for 8 weeks and other fish as control. Gills, hepatopancreas, posterior kidney and spleen were the most affected organs during chronic exposure. Eosinophilic granular cells (EGCs) infiltration and goblet cells hyperplasia in tips of primary lamellae, lamellar lifting, lamellar necrosis and Proliferative interlamellar hyperplasia with fusion in gills, hydropic degeneration and necrosis of the hepatic cells, hemorrhage and necrotic renal tubules and splenic necrosis and depletion of lymphocytes were recorded as histopathological changes.

The present study was designed to investigate the adverse effects of aluminum chloride hexahydrate on the heart, liver and kidneys of rabbits. Twenty-four apparently healthy male and female rabbits were randomly assigned to four groups. The two control groups male (n= 6) and female (n= 6) received subcutaneous injections of physiological saline. The other two Al-treated groups of male (n= 6) and female (n= 6) were given 2.5mg/kg B.W. S/C five times per week for 3 months. At the 6th weeks and the 12th weeks, three rabbits from each group were necropsied and tissues specimens from heart, liver and kidneys were collected and processed for the following histopathologic examination. The heart of both sexes of intoxicated rabbits showed congestion of blood vessels, interfibrillar edema, hemorrhage as well as Zenker's degeneration and necrosis of myocardium. The Liver showed periportal edema, mild fibroplasia, infiltration of inflammatory cells, adenomatous and papillary hyperplasia of bile ductules. The encountered lesions of the kidneys were in the form of vacuolations and necrosis of renal tubular epithelium, with intratubular necrotic cellular debris and hyaline casts. An additional lesion of severe interstitial nephritis was also seen in some areas. It was concluded that the adverse toxic effects of aluminum chloride were time-dependent manner on heart, kidneys and liver of of both sexes of rabbits.

The current study was performed to evaluate the anti-diabetic action of metformin and ginseng in alloxan-induced diabetes in rats. Forty male albino rats were used in this work, ten rats were left without any treatment and kept as a control, the remaining thirty rats were injected with alloxan to induce diabetes and then divided into three equal groups, the first group was kept without any treatment during period of the experiment, the second one treated with metformin (300 mg/kg B.Wt.) and the third one treated with ginseng at dose level of 250 mg/kg B.Wt. for 30 consecutive days. The results showed a significant changes in the hematological parameters, fasting blood glucose level, glycosylated hemoglobin (HbA1C) besides the activity of liver enzymes (aspartate aminotranseferase (AST), alanine aminotranseferase (ALT) and gamma glutamyltransferase (GGT)) and level of total protein in addition to lipid profile (Triglyceride (TG),total cholesterol (TC), very low density lipoprotein (VLDL) and low density lipoprotein (LDL) except high density lipoprotein (HDL)) in all groups compared to control group. The liver and pancreas of all groups were collected and examined histopathologically. Metformin and ginseng have ameliorative effect on biochemical and histopathological alterations caused by hyperglycemia. From our data it could be concluded that ginseng can be used as an effective anti-hyperglycemic and antioxidantagent.