Structural and molecular changes in the rat myocardium following perfluoroctane sulfonate (PFOS) exposure are mitigated by quercetin via modulating HSP 70 and SERCA 2.

Perfluorooctane sulfonate (PFOS) is a man-made fluorinated compound employed in a variety of industrial and civilian applications. Due to its long elimination half-life and promotion of oxidative stress and inflammation, it is one of the most abundant organic contaminants. The present study was designed to determine the cytotoxic effect of PFOS on adult male rat cardiac tissue and to assess the cardioprotective role of the flavonoid quercetin (Que), which possesses antioxidant, anti-inflammatory, and anti-apoptotic properties. Twenty-four adult male Sprague-Dawley rats were randomly divided into four equal groups: Group I (Control). Group II (Que) received Que (75 mg/kg/day for 4 weeks) by oral gavage. Group III (PFOS group): supplemented orally with PFOS (20 mg/kg/day for 4 weeks) and Group IV (PF OS/Que). The rat heart was processed for histological, immunohistochemical, and gene expression studies. The PFOS group showed histological alterations in the myocardium that were partially reversed by the administration of Que. The inflammatory biomarkers (TNF, IL-6, and IL-1), lipid profile, TSH, MDA, and serum cardiac enzymes (LDH and CK-MB) were all altered. These findings collectively suggest that PFOS had adverse effects on the cardiac muscle structure, and these effects were alleviated by quercetin, which is a promising cardioprotective flavonoid.

Spinal cord-wide structural disruption in type 2 diabetes rescued by exenatide "a glucagon-like peptide-1 analogue" via down-regulating inflammatory, oxidative stress and apoptotic signaling pathways.

The mechanisms of spinal cord-wide structural and functional disruption in diabetic patients remain elusive. This study evaluated histopathological alterations of the spinal cord cytoarchitecture in T2DM model of rats and assessed the potential ameliorating effect of exenatide "a potent GLP-1 analogue". Thirty male rats were allocated into three groups; I (control), II (Diabetic): T2DM was induced by high fat diet for 8 weeks followed by a single I.P injection of STZ (25 mg/kg BW) and III (Diabetic/Exenatide): T2DM rats injected with exenatide (10 µg/Kg, S.C. twice daily for 2 weeks). Neurobehavioral sensory and motor tests were carried out and glycemic control biomarkers and indices of insulin resistance and sensitivity were measured. In addition, the spinal cord was processed for histological and immunohistochemical studies besides assessing its tissue homogenate levels of pro-inflammatory/anti-inflamatory cytokines and oxidant/antioxidant biomarkers. Moreover, RT-qPCR was performed to measure the expression of proapoptotic/antiapoptotic and neurotrophic genes. The diabetic rats exhibited thermal hyperalgesia, mechanical allodynia and decreased locomotor activity along with increased serum glucose, insulin, HbA1c, HOMA-IR while, quantitative insulin sensitivity check index (QUICKI) was decreased. Also, IL-1ß NF-kB, MDA increased while IL-10, SOD activity and ß-endorphin decreased in the spinal tissue. Up regulation of caspase-3 and down regulation of Bcl-2, nerve growth factor (NGF) and glial cell-derived neurotrophic (GDNF) in diabetic rats. Also, they exhibited histopathological changes and increased CD68 positive microglia and Bax immunoreactivity in the spinal cord. Subsequent to exenatide treatment, most biomolecular, structural and functional impairments of the spinal cord were restored in the diabetic rats. In conclusion, the neuro-modulating effect of exenatide against diabetic-induced spinal cord affection warrants the concern about its therapeutic relevance in confronting the devastating diabetic neuropathic complications.

Maternal exposure to the environmental pollutant "BDE-47" impairs the postnatal development of rat cerebellar cortex by modulating neuronal proliferation, synaptogenesis, NGF and BDNF pathways.

2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is an environmental contaminant that crosses the blood placental barrier and interferes with the homeostasis of fetal thyroid hormones. AIM OF WORK: This study was designed to investigate the perinatal effect of BDE-47 exposure on the postnatal development of the rat cerebellar cortex. MATERIALS AND METHODS: This study was carried out on 20 pregnant rats and 36 of their offspring. The pregnant rats were divided equally into control and BDE-47 treated mother groups; supplemented orally with BDE-47 (0.2 mg/kg/day from day 8 of gestation until the day of weaning). The offspring of both mother groups were subdivided, according to their developmental age, into three subgroups; PND14, PND21and PND42. SerumT3, T4 and TSH were assessed for dams and their offspring. Testing the motor coordination of the offspring via the rotarod test was conducted. Sections of the cerebellar cortex from offspring subgroups were stained with hematoxylin and eosin alongside immunohistochemical reactions and optical density of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), proliferating cell nuclear antigen (PCNA) and synaptophysin (SYN). Also, the thickness of different layers of the cerebellar cortex was histomorphometrically measured. RESULTS: BDE-47 treated mothers and their offspring subgroups showed a significant decrease in the serum free T3, T4 and increased TSH. The BDE-47 offspring displayed incoordination of the motor activity together with disturbed cytoarchitecture of the cerebellar cortical layers, and impaired migration of its germinative neuronal zones, particularly on PND14 and PND21. Moreover, these offspring displayed a decrease of the immune-expression and optical density of NGF, BDNF in the cerebellar cortical layers with impaired proliferation, and synaptogenesis. CONCLUSION: Maternal exposure to BDE-47 during pregnancy and lactation effectuated a potential deleterious retarding effect on the postnatal development of the rat cerebellar cortex mostly via modulating neuronal proliferation, synaptogenesis, NGF and BDNF pathways secondary to its hypothyroid effect.

Potential long-term developmental toxicity of in utero and lactational exposure to Triclocarban (TCC) in hampering ovarian folliculogenesis in rat offspring.

Triclocarban (TCC), an antimicrobial compound commonly added to a wide range of household and personal hygiene care products, is one of the most prevalent endocrine-disrupting substances (EDS). This study was conducted to elucidate whether in utero and lactational exposure to TCC could adversely affect folliculogenesis and the onset of puberty in female rat offspring. Twenty pregnant Sprague Dawley rats were equally divided into Control and TCC dam groups (supplemented daily with drinking water enriched with 0.5 mg/L of TCC) from gestational day5 to postnatal day21 (PND21). Female offspring, 20 from control and 20 from TCC dams, were subdivided into 4 subgroups (PND21, PND28, PND35 & PND42). The day of vaginal opening and first estrous cycle were determined. Ovarian sections of the offspring were processed for H&E staining and for immunohistochemical expression of Ki67, Caspase-3 and androgen receptors (AR) on the granulosa cells of ovarian follicles. Follicular count and atretic index were assessed besides, serum estradiol, progesterone, FSH and LH, C-reactive protein (CRP), malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured. TCC offspring exhibited a significant delay in the onset of puberty and impedance of normal transition of the primordial follicles to more developed ones with altered cyctoarchitecture. Also, TCC decreased follicular count, proliferation and gonado-somatic index while it increased atretic index, apoptosis and AR of the granulosa cells along with disturbance of the feminine hormonal profile and oxidant/antioxidant balance. This study highlighted the potential long-term consequences of in utero and lactational exposure to TCC on the postnatal development of the ovary in rat offspring.

Histological and imunohistochemical alterations of hippocampus and prefrontal cortex in a rat model of Alzheimer like-disease with a preferential role of the flavonoid "hesperidin".

Alzheimer's disease (AD) is a chronic age-related neurodegenerative disease characterized by degeneration of the central cholinergic neurons, inflammation and oxidative stress in the basal forebrain, prefrontal cortex and hippocampus. Hesperidin (Hesp) is one of the flavonoids havinganti-inflammatory and anti-oxidative properties in some neurodegerative brain lesions. To investigate the possible neuroprotective role of Hespin an AD-like rat model induced experimentally by Scopolamine (Scop). Forty adult male Sprague Dawley rats were randomly allocated into four groups. Group I-(Control), group II-(Hesp) (supplemented orally with 100 mg/kg Hesp for 28 days), group III-(AD) (injected i.p with 1 mg/kg Scop for 9 days) and group IV-(Hesp/AD). At the end of the experiment, behavioral (Y-maze test) and biochemical analysis were carried out along with histological, immunohistochemical and morphometric studies of the hippocampus and prefrontal cortex. AD rats displayed memory impairment in the behavioural paradigm with a concomitant increase of serum TNF-α and IL-1ß, while IL-10 decreased significantly. Also, there was a rise of amyloid beta-42 (Aß-42), acetylcholinesterase (AChE) activity and malondialdehyde (MDA) together with a decrease of reduced glutathione (GSH) in hippocampal and prefrontal homogenate. In addition, sections of the hippocampus and prefrontal cortex revealed obvious histopathological changes, overexpression of p-Tau protein and glial fibrillary acidic protein (GFAP) with a decrease in the expression of synaptophysin (SYN). Contradictorily, pre-treatment with Hesp offset the spatial memory deficits, redox imbalance, Aß-42 and AChE over activity as well as preserved the histological architecture and attenuated the raised p-Tau protein and GFAP while upregulated SYN immuoreactivity of AD rats. Collectively, our results highlight the potential mitigating role of Hesp in AD-like state in rats and this may presumably raise the possibility of its future implementation as a prophylactic remedy against AD in humans.

Histological effects of bisphenol-A on the reproductive organs of the adult male albino rat

Bisphenol-A (BPA) is widely used in the environment. The objective of this study was to investigate the histological reproductive toxicity of BPA in the adult male albino rats. Forty-five adult male albino rats were divided into 3 groups. Group I received normal saline orally daily (negative control); Group II received corn oil (0.5 ml/day) orally daily (positive control, and Group III were treated with BPA in a dose of 25 mg/kg B.W dissolved in corn oil for 30 days orally. Specimens from the testis, epididymis, prostate and seminal vesicles were collected for light microscopic examination. Blood samples were collected for serum testosterone level assessment. BPA caused histopathological alterations in the epithelium and connective tissues of all organs. Results of the serum testosterone level statistical analysis showed a highly significant decrease in BPA-treated group (III) as compared to the control groups (I & II). The epithelium of the accessory sex glands (prostate and seminal vesicles) responds to BPA by proliferative differentiation. The mean area percentage of collagen fibers stained with Masson's trichrome measured in the stroma of all organs was significantly increased. Also, there was a significant increase in the area percentage of positive inducible nitric oxide synthase (iNOS) immunoreactions in all organs. In conclusion, BPA induced DNA oxidative damage via iNOS activity in all reproductive organs

No disponible