The possible protective role of vitamin C versus melatonin on potassium dichromate induced changes in rat thyroid gland: light and electron microscopic study.

Potassium dichromate is widely used in various laboratory and industrial applications. Vitamin C and melatonin are well-known antioxidants. Study the microscopic and morphometric alterations in the thyroid gland in adult male albino rats after the administration of potassium dichromate for successive 2 months and also to assess the possible protective effect of vitamin C versus melatonin on these changes. Sixty adult male albino rats were randomly divided into four main groups. Group I (The control group). Group II received potassium dichromate (25 mg/kg/day) dissolved in distilled water by intraperitoneal (i.p) injection for 2 months. Group III received the same dose of potassium dichromate with vitamin C (120 mg/kg/day) orally through an intragastric intubation. Group IV received the same dose of potassium dichromate and melatonin (10 mg/kg/day) as an i.p injection. Thyroid gland samples were prepared for light and electron microscopic studies. Potassium dichromate group demonstrated congested blood vessels, follicular hyperplasia, follicular enlargement with degenerated lining cells that were exfoliated in the lumen. The parafollicular cells appeared with darkly stained nuclei. PAS reaction showed weak reaction in the colloid with an abnormal pattern of vacuolization. A highly significant increase in the percentage area of fibrosis was detected in Mallory trichrome sections. Ultrastructurally, follicular cells and parafollicular cells appeared irregular in shape with dark, small heterochromatic nuclei. Small, electron-dense granules in the parafollicular cells were found. Potassium dichromate and vitamin C-treated group III showed partial improvement of the thyroid gland. The PAS reaction showed that nearly all the follicles were more or less similar to those of the control group. A significant decrease in the percentage area of fibrosis in group III was found as compared to those in group II. Potassium dichromate and melatonin-treated group showed that the thyroid gland was nearly similar to that of the control group. Vitamin C and melatonin could partially protect against potassium dichromate induced changes in the thyroid gland and the protective effect of melatonin was better than that of vitamin C.

Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

BACKGROUND: Depression is one of the important world-wide health problems. OBJECTIVES: This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. MATERIALS AND METHODS: Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). RESULTS: OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. CONCLUSION: Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies.

Nootkatone Counteracts Melamine-Mediated Nephrotoxicity via Modulation of Intermediate Filament Proteins, Oxidative, Inflammatory, and Apoptotic Events.

Background: Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage. Methods: Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg). Results: The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK's ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1ß and TNF-α, besides downregulation of NF-κB and IL-1ß expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features. Conclusion: These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.

Ineffectiveness of topiramate and levetiracetam in infantile spasms non-responsive to steroids. Open labeled randomized prospective study.

OBJECTIVE: To compare the effectiveness of 2 novel antiepileptic drugs, topiramate and levetiracetam, as a second line treatment for infantile spasm when oral steroids fail. METHODS: Forty infants under 2 years with clinically- and EEG-proven infantile spasms that did not respond to prednisone (2mg/kg/day in 2 divided doses) were recruited and randomized into 2 groups. They were randomly assigned to either topiramate (group 1; 1mg/kg/day for 3 days then increased by 1mg/kg/day every third day up to 6mg/kg/day) or levetiracetam (group 2; 10mg/kg/day for 5 days and then increased by 10mg/kg/day every 5 days up to 60mg/kg/day). The study was conducted in the Pediatric Neurology Department at the National Neuroscience Institute of King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia between January 2008 and December 2010. RESULTS: Of the 20 patients included in the final data analysis, 11 (55%) were administered topiramate and 9 (45%) levetiracetam. Eighteen patients did not respond to the first drug, and subsequently to the other drug when crossed-over. Two patients with infantile spasm responded to either one drug without crossover. Their EEGs improved with time. CONCLUSION: The present study demonstrated the ineffectiveness of topiramate and levetiracetam suggesting current treatment modalities are grossly inadequate underscoring the urgent need for more research efforts to overcome current deficiencies. Two patients with cryptogenic infantile spasm responded to treatment suggesting the potential for treatment of such patients with these 2 drugs, and merits further multicenter investigation.

Crucial Role of PLGA Nanoparticles in Mitigating the Amiodarone-Induced Pulmonary Toxicity.

BACKGROUND: Amiodarone (AMD) is a widely used anti-arrhythmic drug, but its administration could be associated with varying degrees of pulmonary toxicity. In attempting to circumvent this issue, AMD-loaded polymeric nanoparticles (AMD-loaded NPs) had been designed. MATERIALS AND METHODS: AMD was loaded in NPs by the nanoprecipitation method using two stabilizers: bovine serum albumin and Kolliphor® P 188. The physicochemical properties of the AMD-loaded NPs were determined. Among the prepared NPs, two ones were selected for further investigation of spectral and thermal analysis as well as morphological properties. Additionally, in vitro release patterns were studied and kinetically analyzed at different pH values. In vitro cytotoxicity of an optimized formula (NP4) was quantified using A549 and Hep-2 cell lines. In vivo assessment of the pulmonary toxicity on Sprague Dawley rats via histopathological and immunohistochemical evaluations was applied. RESULTS: The developed NPs achieved a size not more than 190 nm with an encapsulation efficiency of more than 88%. Satisfactory values of loading capacity and yield were also attained. The spectral and thermal analysis demonstrated homogeneous entrapment of AMD inside the polymeric matrix of NPs. Morphology revealed uniform, core-shell structured, and sphere-shaped particles with a smooth surface. Furthermore, the AMD-loaded NPs exhibited a pH-dependent and diffusion-controlled release over a significant period without an initial burst effect. NP4 demonstrated a superior cytoprotective efficiency by diminishing cell death and significantly increasing the IC50 by more than threefold above the pure AMD. Also, NP4 ameliorated AMD-induced pulmonary damage in rats. Significant downregulation of inflammatory mediators and free radicle production were noticed in the NP4-treated rats. CONCLUSION: The AMD-loaded NPs could ameliorate the pulmonary injury induced by the pure drug moieties. Cytoprotective, anti-fibrotic, anti-inflammatory, and antioxidant properties were presented by the optimized NPs (NP4). Future studies may be built on these findings for diminishing AMD-induced off-target toxicities.

Thymoquinone Upregulates Catalase Gene Expression and Preserves the Structure of the Renal Cortex of Propylthiouracil-Induced Hypothyroid Rats.

BACKGROUND: The association between hypothyroidism and renal diseases has been described in many studies. Nigella Sativa was among the recently reported natural product that has the potential to prevent renal tissue damage and fibrosis. The aim of this study was to evaluate the possible protective effect of thymoquinone on the structure of the renal cortex of hypothyroid rats and explore the mechanism behind it. METHODS: An experimental model of hypothyroidism was induced in adult male Wistar rats by administration of propylthiouracil (6 mg/kg/body weight). One hypothyroid group was treated with thymoquinone at the dose of 50 mg/kg/body weight and compared to the untreated group. Thyroid function and oxidant/antioxidant status were assessed in the serum. Catalase gene expression was assessed using the real-time polymerase chain reaction. The kidney was assessed both histologically and immunohistochemically. RESULTS: Administration of propylthiouracil resulted in a significant decrease in the serum levels of nitric oxide, reduced glutathione, and superoxide dismutase activity while the level of malondialdehyde significantly (p < 0.001) increased. Administration of thymoquinone alleviated this effect on the thyroid hormones and significantly increased the serum levels of antioxidants. Thymoquinone significantly (p < 0.001) upregulated catalase transcription by about 24-fold and could block the hypothyroidism-induced glomerular and tubular injury. CONCLUSION: Thymoquinone may have a potential protective effect against hypothyroidism-induced renal injury acting through the attenuation of the oxidative stress and upregulation of renal catalase gene expression.

The protective role of musk on salivary glands of mice exposed to chronic unpredictable mild stress.

This study assessed the impact of chronic unpredictable mild stress (CUMS) on the structure of mouse salivary glands and the role of musk in alleviating this impact. Forty male albino mice were distributed equally into four groups; control (untreated), CUMS (exposed to CUMS for 4 weeks), CUMS+fluoxetine (FLU) (exposed to CUMS then treated with FLU, CUMS+musk (exposed to CUMS then treated with musk). Behavioral changes and serum corticosterone levels were assessed at the end of the experiment. The submandibular and parotid glands were dissected out and processed for histopathological and immunohistochemical examination using antibodies against alpha smooth muscle actin (ASMA) and brain-derived neurotropic factor (BDNF). Exposure to CUMS significantly (P < 0.001) increased the serum corticosterone level and induced depression. CUMS also induced vacuolation in acinar cells along with a significant (P < 0.001) reduction of ASMA immunoexpression, indicating an effect on myoepithelial cells, and a significant (P < 0.001) increase of BDNF expression in the gland ductal system. Both FLU and musk alleviated the CUMS-induced behavioral, biochemical and histopathological changes in the salivary glands. In conclusion, musk ameliorates stress-induced structural changes in mouse salivary glands. This effect might be mediated through up-regulation of BDNF secretion by the glands.

Aging related changes of retina and optic nerve of Uromastyx aegyptia and Falco tinnunculus.

Aging is a biological phenomenon that involves gradual degradation of the structure and function of the retina and optic nerve. To our knowledge, little is known about the aging-related ocular cell loss in avian (Falco tinnunculus) and reptilian species (Uromastyx aegyptia). A selected 90 animals of pup, middle, and old age U. aegyptia (reptilian) and F. tinnunculus (avian) were used. The retinae and optic nerves were investigated by light and transmission electron microscopy (TEM) and assessments of neurotransmitters, antioxidant enzymes (catalase, superoxide dismustase and glutathione s transferase), caspase-3 and -7, malonadialdhyde, and DNA fragmentation. Light and TEM observations of the senile specimens revealed apparent deterioration of retinal cell layers, especially the pigmented epithelium and photoreceptor outer segments. Their inclusions of melanin were replaced by lipofuscins. Also, vacuolar degeneration and demyelination of the optic nerve axons were detected. Concomitantly, there was a marked increase of oxidative stress involved reduction of neurotransmitters and antioxidant enzymes and an increase of lipid peroxidation, caspase-3 and -7, subG0/G1 apoptosis, and P53. We conclude that aging showed an inverse relationship with the neurotransmitters and antioxidant enzymes and a linear relationship of caspases, malondialdhyde, DNA apoptosis, and P53 markers of cell death. These markers reflected the retinal cytological alterations and lipofuscin accumulation within inner segments.

Aging-related changes of optic nerve of Wistar albino rats.

Aging is a biological phenomenon that involves an increase of oxidative stress associated with gradual degradation of the structure and function of the optic nerve. Gender differences and subsequent deterioration of optic nerve are an interesting topic, especially because there is little published work concerning it. One hundred male and female Wistar albino rats' with ages 1, 6, 18, 24, and 30 months (n = 20 equal for male and female) were used. At the time interval, optic nerve was investigated by light and transmission electron microscopy (TEM), assessments of antioxidant enzymes (catalase, superoxide dismustase, and glutathione-S-transferase), caspase 3 and 7, malondialdhyde, flow cytometry of DNA, annexin v, and CD8, immunochemistry of vascular endothelial growth factor (VEGF), CD31, and CD45, and single-strand DNA fragmentation. Light and TEM observations of the older specimens (24 and 30 months) revealed apparent deterioration of optic nerve axons, abundant oligodendrocytes with pyknotic nuclei, swollen astrocytes, angiogenesis, vacuolar degeneration, and mitochondrial damage. Females were highly susceptible to aging processes. Concomitantly, there was a marked reduction of antioxidant's enzymes and an increase of lipid peroxidation and apoptotic markers. Old age exhibited a marked increase of G1 apoptosis, UR and LR of annexin V and CD8 as well as increased immuno-positive reaction with VEGR, CD31 and CD45. We conclude that aging contributed to an increase of oxidative stress resulting from damage of mitochondria in axons, oligodendrocytes, and astrocytes. Age-related loss of optic nerve axons is associated with multifactorial agents including reduction in antioxidant enzymes, disruption of vasculature, astrocyte, and oligodendrocyte, demyelination, and damage of mitochondria, which enhance the liberation of reactive oxygen species as assessed by an increase of apoptotic markers malondialdhyde and caspase 3 and 7.