Modulation of inflammatory mediators involved in the antinociceptive and anti-inflammatory effects of a new thioamide derivative: thiocyanoacetamide.

Inflammatory pain is part of the body's defense mechanism and plays an important role in the healing process. Although some drugs are efficient and intensively used for their potent anti-inflammatory properties, they present problematic side effects. The aim of this study was to evaluate the anti-nociceptive effect of the thiocyanoacetamide (Thm) compared to paracetamol (Para), dexamethasone (Dex) and morphine (Morph) and to study inflammatory mediators on models of acute inflammatory pain in rats using the formalin injection test in the hind paw of rats as chemical stimulus. The obtained results showed significant modulation of pain by Thm pretreatment with a maximum at an effective dose (10 mg/kg) proved by the absence of licking and biting of the affected paw during the early and late phases of inflammation. This effect was comparable to Dex at 10 mg/kg, Para at 400 mg/kg and less than Morph at 5 mg/kg pretreatment doses. The study of anti-inflammatory targets showed that Thm pretreatment maintained plasma serotonin release at normal level compared to the negative control group (T-) and corrected the decrease in the plasma level of prostaglandins after inflammatory induction with no variation in the level of histamine in different groups. The evaluation of inflammation mediators demonstrated that the pretreatment with Thm induced the decrease in the amount of both IL-1 Beta and TNF alpha in plasma and the increase in their amount in the tissue of the injection site. The Thm has been promoted as an anti-nociceptive drug that induces modulation of inflammatory mediators.

Olea europaea L. leaf extract mitigates oxidative and histological damage in rat heart tissue exposed to combined noise and toluene: An experimental study.

In many occupational settings, workers are frequently exposed to toluene and noise. However, the individual and combined effects of these exposures on the cardiovascular system have not been fully elucidated. Therefore, this study aimed to investigate the impact of simultaneous exposure to toluene and noise on the rat heart, while also evaluating the potential preventive effect of olive leaf extract (OLE). Forty-eight male Wistar rats were randomly assigned to eight groups (n = 6/group): control group (C), control group that received OLE (C + OLE), group exposed to noise (N), group exposed to noise and receiving OLE (N + OLE), group exposed to toluene (T), group exposed to toluene and receiving OLE (T + OLE), group co-exposed to noise and toluene (NT), and group co-exposed to noise and toluene and receiving OLE (NT + OLE). The rats in this study were subjected to simultaneous exposure to toluene and noise for a duration of six weeks, within a custom-built plexiglass chamber. Toluene was administered at a concentration of 300 ppm, while the noise level was set to 85 dB(A). The exposure chamber was equipped with a generation system, an exposure system, and a monitoring system, ensuring precise and accurate exposure conditions. After the six-week period, heart and blood samples were collected from the rats for subsequent analysis. Plasma levels of cholesterol (CHOL), triglycerides (TG), lactate dehydrogenase (LDH), and creatine kinase (CK) were measured, and histopathological investigation was conducted using HE staining. Additionally, superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) levels in heart tissue were measured. Our results showed that simultaneous exposure to noise and toluene altered CHOL, TG, LDH, and CK levels, and also caused an increase in lipid peroxidation levels and superoxide dismutase activity, along with a decrease in catalase activity in the heart. A significant alteration in the myocardium was also observed. However, treatment with OLE was found to modulate these oxidative and histological changes, ultimately correcting the deleterious effects induced by the combined exposure to noise and toluene. Therefore, our study suggests that OLE could be a potential preventive measure for individuals exposed to toluene and noise in industrial settings.

Evaluation of antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide in rats.

OBJECTIVE: Acute pain is the most common type of pain. The aim of the present work was carried out to study the antinociceptive effect and pharmacological mechanisms of thiocyanoacetamide (Thm) in rats exposed to thermal pain stimulus. MATERIALS AND METHODS: The anti-nociceptive effect of the newly synthesized compound, Thm was studied in comparison to that of paracetamol (Para), dexamethasone (Dex), and morphine (Morph) at different doses using a hot plate test at a constant temperature of 48.0 ± 0.5°C. During this test, the latency time (LT) was measured when rats express pain behavior. Then, the pharmacological mechanisms were determined using receptor-antagonist drugs. RESULTS: Firstly, the obtained result showed pain modulation of the pretreated rats with Thm at 10 mg/kg dose proved by the delay of latency time during the thermal test. This significant antinociceptive activity of the thiocyanoacetamide was more effective than that of paracetamol or dexamethasone and less than that of morphine. Second, the pretreatment with acebutolol or risperidone antagonist drugs of, respectively, adrenergic and serotonin receptors demonstrated the elimination of pain modulation with Thm 10 mg/kg dose proved by a short latency time of rat's response in hot plate test. In this case, the pharmacological mechanism of Thm was characterized by the involvement of adrenergic and serotoninergic systems. CONCLUSIONS: It may be concluded that Thm constitutes a promising antinociceptive drug including beta-adrenergic and serotoninergic targets. The present study warrants further investigation to determine the side effects of this compound.

Kefir milk consumption decreases sperm alterations due to the high-fat diet in adult male rats.

Over the past decades, an increase of male infertility through the decrease of sperm count has been noted. It has been suggested that environmental factors and lifestyle could a negative impact over sperm quality. Among these factors, the consumption of foods high in fat, which leads to overweight and obesity, can negatively influence fertility. The present study was designed to highlight the protective effect of Kefir, natural probiotic, against the decline in sperm quality related to fat high diet. Thirty adult rats were divided into four groups: Control (1 ml/100 g of body weight (bw) of semi-shimmed cow milk), KM (1 ml/100 g bw of Kefir milk), HFD (1 ml/100 g bw of semi-shimmed cow milk + high-fat diet) and KM/HFD (1 ml/100 g bw Kefir milk + high-fat diet). After 60 days of treatment, sperm quality, biochemical assays of lipids profil, blood cell count and histological examination in testis were assessed. The results described an improved of sperm density (64.28 106  ml vs 54.14 106  ml), viability (70.50% vs 55.33%), mobility (65.40% vs 63.60%) and morphological abnormalities (52% vs 25%) in the KM/HFD group compared to HFD group. In the same group, the lipid profil (Triglycerides (128.39 mg/dl vs 102.85 mg/dl), C-LDL (13.65 mg/dl vs 15.32 mg/dl) and C-HDL (23.21 mg/dl vs 19.15 mg/dl)) was corrected compared to HFD group. The histological observation of testis revealed a normal spermatogenesis compared to seminiferous tubules of HFD group, which showed a serious disruption and damage of testicular epithelium exerted by the high-fat diet. These findings corroborated the previous beneficial effect of Kefir and brought new insights into its beneficial effect against deteriorated spermatogenesis in obese adult rats.

In vivo exposure to a new 2-cyano-2-p-nitrophenyl-N-benzylthioamide decreases doxorubicin-triggered structural damages in the mature testis.

The use of doxorubicin (DOX) in clinical practice continues to be challenged by its severe toxicity. DOX cytotoxic activity is not only directed against malignant tumours, given that the treatment will damage healthy tissues as well leading to irreversible injuries. This study aimed to address the in vivo effects of DOX and its co-administration with a new analog of thioamide; thiocyanoacetamide (TA) on the germinal epithelium. Thus, male rats received either intravenous injection (iv) of 0.03 mg/kg of body weight/week, 0.9% NaCl and were regarded as the control group (CTR), treated with DOX (3.7 mg/kg/week iv), TA [10 mg/kg/day intragastrically (ig)] or a co-supplementation of DOX and TA. After 50 days, the left testes were dissected and used for toluidine blue, periodic acid-Schiff (PAS) staining (to evaluate the change in polysaccharides/glycoproteins content), and transmission electron microscopy (TEM) (to assess the morphological damages). To estimate the impact of the test compounds on mitochondrial biogenesis, the expression of NAD-dependent deacetylase sirtuin-3 (SIRT-3) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were evaluated by immunofluorescence. Apoptotic cells were observed using Hoechst 33324 fluorescent staining. Data showed testicular injuries in the DOX-treated group, manifested by a significant decrease in total germ cell (GC) number, alteration of Sertoli cell (SC) nucleolus, anchoring junction, along with modifications of the basement membrane (BM) regularity and increase in apoptotic cell count. Mitochondrial aspect and SIRT-3 and PGC-1α expression in the testis were unaffected by the DOX. Co-therapy increased GC number, decreased apoptotic cell count, and restored the BM and anchoring junction regular aspects. This study provides novel insights into understanding DOX-mediated impairment in rats' testis and might offer some basis for the emerging new alternative therapeutic schemes in male patients undergoing chemotherapy.

Protective and Curative Effects of Aqueous Extract of Terfezia Boudieri (Edible Desert Truffle Specie) against Paracetamol Acute Toxicity in the Rat.

The current study was aimed to evaluate the protective and curative effect of aqueous extract of edible desert truffle specie (Terfezia boudieri) against rat's liver and kidney injuries induced by paracetamol (PCM). Terfezia boudieri was genetically identified by PCR and then sequencing (Genbank NCBI: LT718236.1). Terfezia boudieri aqueous extract (TBAE) was characterized by antioxidant capacity evaluated by 1,1-diphenyl-2-picryl-hydrazyl test (EC50 = 0.415 mg/ml). LC-MS analysis shows that TBAE contains several actives biomolecules such as B3 vitamin (2.73 ± 0.3 mg/100g dm), quinic acid (2 ± 0.22 mg/100g dm), chlorogenic acid (0.18 ± 0.02 mg/100g dm) and quercetin-3-o-rhamonoside (0.09 ± 0.01 mg/100g dm). Liver and kidney Biochemical parameters showed no significant variation in rat's plasma treated with PCM and/or TBAE. However, the histological studies showed that the liver injuries induced by PCM were characterized by hemorrhage and inflammation. The pretreatment by TBAE showed preservation of normal liver and kidney architecture, this finding suggests its protective effects on these two organs. The co-treatment by TBAE reduced the PCM hepatotoxicity proved by normal central vein and small vacuols. In addition, TBAE reduced kidney PCM toxicity proved by less area inflammation and normal glomerulus. Therefore, TBAE is promoting eventual protective and curative drug against acute toxicity.

Matrix metalloproteinase-7 could be a predictor for acute inflammation in psoriatic patients.

PURPOSE: The pathogenesis of psoriasis is characterized by a disruption of extracellular matrix (ECM) in which matrix metalloproteinases (MMPs) participate actively. We aimed to determine MMP-7 level and its association with the inflammatory response in order to determine its usefulness as a biomarker for psoriasis prediction. We also aimed to determine its distribution in uninvolved and involved psoriatic skin to evaluate the probable role of MMP-7 in psoriasis pathogenesis. MATERIALS AND METHODS: We recruited 108 psoriatic patients and 133 healthy controls. MMP-7, tissue inhibitors of metalloproteinases (TIMPs) and interleukin-6 (IL-6) levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) assay. MMP-7 expression was detected by Immunohistochemistry (IHC) study. RESULTS: ECM turnover and inflammatory biomarker levels were significantly higher in psoriatic patients. MMP-7 revealed to be independently associated to psoriasis even after adjustment for different models. The area under the curve (AUC) of MMP-7 and inflammation Z-score were similar. MMP-7 was positively correlated with IL-6 and inflammation Z-score. Psoriasis severity (PASI) was correlated significantly with IL-6 (p = 0.007). The MMP-7 expression was detected in the epidermis of involved and uninvolved psoriatic skin. In involved skin, MMP-7 was expressed by basal and mostly suprabasal keratinocytes. In uninvolved skin, expression of MMP-7 was restricted to basal keratinocytes. CONCLUSION: MMP-7 is independently associated to psoriasis disease and to inflammatory response which make it a potential biomarker for this dermatosis.

The Prognostic Significance of IGF-1R and the Predictive Risk Value of Circulating IGF-1 in Tunisian Patients with Laryngeal Carcinoma.

The aim was to evaluate the clinical impact of IGF-1/IGF-1R in Tunisian laryngeal carcinoma. A high IGF-1R immunohistochemical expression was found in our series (81.43%). A tendency toward an association between IGF-1R expression and lymph node metastasis was found (p = 0.068). Patients with positive IGF-1R expression showed a short disease free survival (p = 0.053) and a high recurrence rate. Furthermore, circulating IGF-1 levels sera, detected by ELISA, were higher among patients compared to controls (p < 0.001). IGF-1R might have a prognostic significance and could be a factor of tumor recurrence. However, high levels of IGF-1 increase the risk of developing of LSCC disease.

Post-weaning xenohormone intake affects adult rat submandibular gland in a sex-dependent manner.

OBJECTIVES: We previously reported that maternal exposure to genistein and vinclozolin, ingested alone or in combination, affects submandibular salivary glands of rat offspring. Here, we investigated the responsiveness of submandibular gland when such xenohormone exposure occurs later in life. MATERIALS AND METHODS: Chemicals were given orally to male and female Wistar rats (1 mg/kg body weight per day), from weaning to adulthood. Submandibular glands and plasma were collected at postnatal day 100 for histologic and molecular analysis. RESULTS: Whereas no effect was observed in females, increases in granular convoluted tubules area coupled with a modification of salivary secretions were found in male submandibular glands. Genistein and vinclozolin similarly increased the mRNA expression of Cystatin C, Mucin 10, Growth factors, and plasmatic EGF. Negative correlations were found between the expressions of androgen receptor and EGF (-0.34; p < 0.05), TGFα (-0.52; p < 0.01), Mucin 10 (-0.43; p < 0.05), and Cystatin C (-0.42; p < 0.05) as well as between progesterone receptor and EGF (-0.56; p < 0.01). The Spearman correlation test revealed also a positive correlation between salivary EGF-mRNA expression and EGF in plasma (+0.32; p < 0.05). CONCLUSION: Our findings confirm the sex-dependent sensitivity of submandibular salivary glands to dietary xenohormones and underline the influence of the exposure period.

Semen Parameter Alteration, Histological Changes and Role of Oxidative Stress in Adult Rat Epididymis on Exposure to Electronic Cigarette Refill Liquid.

Electronic cigarettes (e-cigarettes) are devices intended to substitute conventional cigarettes, with the aim of being less harmful. In a previous report, we showed that intraperitoneal (i.p.) injection of e-cigarette liquid (E-liquid), with or without nicotine, induced toxicity in the testes of Wistar rats by disrupting oxidative balance and steroidogenesis. In the present work, we further evaluated the impact of e-liquid with or without nicotine on the epididymis of rats using the same procedure. Results showed that e-liquid treatments led to alteration of semen parameters, with a significant drop of at least 50% in sperm vitality, a significant increase of morphologically abnormal spermatozoa and an imbalance of redox status in comparison to the control group. A significant raise of 1.4 fold, compared to the untreated rats, in myeloperoxidase (MPO) granules after both treatments was recorded, suggesting an inflammatory state. Histopathological examination confirmed a marked reduction in sperm count in the cauda epididymis. Data of this study suggest that the pro-oxidant properties of e-liquid with or without nicotine, in addition to testicular defects, could lead to an inflammatory state in the epididymis, causing alterations in the semen parameters. These data provide additional information on the impact of e-liquid on the reproductive system.

Grape seed and skin extract protects against arsenic trioxide induced oxidative stress in rat heart.

Arsenic is a metalloid found in water, soil, and air from natural and anthropogenic sources, and is commonly found in inorganic as well as organic forms. The clinical use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) is limited by its cardiotoxic side effects. Grape seed and skin extract (GSSE) is a polyphenolic mixture with antioxidant properties. This study aimed to evaluate the protective effect of GSSE on arsenic-induced cardiac oxidative stress and injury. Animals exposed to 2.5 mg/kg As2O3 for 21 days exhibited a relevant increase in heart lipoperoxidation, protein carbonylation, and inflammation, as well as a drop in the activity of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx). In addition, As2O3 disturbed heart lipidemia and lipase activity, transition metals distribution and the associated enzymes, intracellular mediators such as calcium and the associated calpain activity, as well as myocardial architecture. Treatment with 4 g/kg GSSE protected against most of the deleterious effects provoked by As2O3. Our data suggest that GSSE has the potential to protect against As2O3-induced cardiotoxicity.

Impact of e-cigarette refill liquid exposure on rat kidney.

Electronic-cigarettes (e-cigarette), the alternative to classic cigarettes are becoming extremely popular but their safety is not still established. Recent studies have showed cytotoxic effects of the electronic cigarette and its recharge e-liquid, in vitro. The present study was designed to evaluate e-cigarette liquid nephrotoxicity in rats. For this purpose, 32 rats were treated for 28 days as follows: Control group was injected intraperitoneally with NaCl 9 g/l; e-cigarette 0% treated group received an intraperitoneal injection of e-liquid without nicotine diluted in NaCl 9 g/l, e-cigarette treated group, received an intraperitoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l and nicotine-treated group received an intraperitoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l. In nicotine group, creatinine level was increased, whereas urea and acid uric levels were decreased. In e-liquid-exposed groups, levels of uric acid and mainly urea were lower. Interestingly, after e-liquid exposure, oxidative stress status showed increased total protein and sulfhydril content, whereas superoxide dismutase and catalase activities were decreased. However, the levels of lipid peroxides were not increased after e-liquid exposure. Histological studies identified excess of cells with reduced and dark nuclei exclusively located in the renal collecting ducts. Thus, e-liquid seems to alter anti-oxidant defense and to promote minor changes in renal function parameters. This preliminary study raises some flags about possible nephrotoxicity of e-cigarette liquids in rats. As some features observed in rats may not be observed in human smokers, additional studies are needed to further qualify conclusions that might be applicable to actual users of e-cigarettes.

Impact of e-cigarette refill liquid with or without nicotine on liver function in adult rats.

This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.

Cochlear neuropathy in the rat exposed for a long period to moderate-intensity noises.

Damaging effects on the cochlea of high-intensity acoustic overexposures have been extensively documented, but only few works have focused on the danger of moderate noise levels. Using scanning and transmission electron microscopy, we explored the noise-induced neuroepithelial changes that occur in the cochlea of rats subjected to moderate intensities, 70 and 85 dB SPL, for an extended period of time (6 hr/day over 3 months). Although the full quota of outer and inner sensory hair cells remained present, we detected discrete abnormalities, likely resulting from metabolic impairment, in both types of hair cell within the basal region of the cochlea. In contrast, important noise-dependent losses of spiral ganglion neurons had occurred. In addition, we found cytoplasmic accumulations of lipofuscin-like aggregates in most of the surviving cochlear neurons. These results strongly suggest that noise levels comparable to those of certain working environments, with sufficient exposure duration, pose a severe risk to the cochlea. Moreover, our data support the notion that long-duration exposure to moderate noise is a causative factor of presbycusis.

Assessment of cochlear effects and extra-auditory disorders in male rats exposed repetitively to low noise.

BACKGROUND: The noise is considered as a factor of environmental stress, causing a wide range of health effects such as acoustic, cardiovascular, nervous and endocrine systems. PURPOSE: The present study was conducted to examine the affects of repeated exposure to noise on the peripheral auditory system, adrenal gland and heart tissue. METHOD: The White strain rats "Wistar" were exposed to chronic and repetitive exposure noise at two different intensity levels of 70 and 85dB (A). The noise level was generated by the Audacity® software to an octave-band noise (8616 kHz). The sound exposure duration was 6 hr/day, 5 days per week for 3 months. Quantitative and qualitative investigations were performed by using electron microscopy. The ganglion neuron counting was examined via light microscopy. RESULTS: The results show that exposure to sound intensities 70 and 85 dB (A) for long periods, lead to changes in the morphological structure of the cochlea (inner ear), adrenal cortex and cardiac tissue which involve cell disruption which over time can lead to pathological effects. CONCLUSION: This study provides morphological evidence that repetitive exposure noise at moderate sound levels to 70 and 85 dB (A) induces changes in the peripheral auditory system, the adrenal cortex and heart tissue.

Protective effect of grape seed and skin extract against high-fat diet-induced liver steatosis and zinc depletion in rat.

BACKGROUND: Obesity is a tremendous public health problem, characterized by ectopic deposition of fat into non-adipose tissues as liver generating an oxidative stress that could lead to steato-hepatitis. Grape seed and skin extract (GSSE) is a complex mixture of polyphenolics exhibiting robust antioxidative properties. AIM: We hypothesize that GSSE could protect the liver from fat-induced lipotoxicity and have a beneficial effect on liver function. METHODS: Hepatoprotective effect of GSSE was measured by using an experimental model of fat-induced rat liver steatosis. Male rats were fed a standard diet or a high-fat diet (HFD) during 6 weeks and treated or not with 500 mg/kg bw GSSE. Lipid deposition into the liver was assessed by triglyceride, cholesterol and phospholipid measurements. Fat-induced lipoperoxidation, carbonylation, depletion of glutathione and of antioxidant enzyme activities were used as oxidative stress markers with a special emphasis on transition metal distribution. RESULTS: HFD induced liver hypertrophy and inflammation as assessed by high liver transaminases. HFD also induced an oxidative stress characterized by increased lipid and protein oxidation, a drop in glutathione and antioxidant enzyme activities as glutathione peroxidase and superoxide dismutase and a drastic depletion in liver zinc. Importantly, GSSE prevented all the deleterious effects of HFD treatment. CONCLUSIONS: Data suggest that GSSE could be used as a safe preventive agent against fat-induced liver lipotoxicity which could also have potential applications in other non-alcoholic liver diseases.

Morphological changes of adrenal gland and heart tissue after varying duration of noise exposure in adult rat.

Noise was considered an environmental stressor causing a wide range of health effects such as acoustic, cardiovascular, nervous, and endocrine systems. The present study was performed to examine the effects of a repeated noise exposure on adrenal gland and heart tissue. The results showed that exposure to moderate intensity sound (70 dB[A]) causes time-dependent changes in the morphological structure of the adrenal cortex that involve disarrangement of cells and modification in thickness of the different layers of the adrenal gland. The experiment revealed important changes depending on exposure duration in the morphological structure of heart tissue that causes irreversible cell damage leading to cell death or necrosis.

Qualitative and quantitative assessment of noise at moderate intensities on extra-auditory system in adult rats.

Noise has long been realized as an environmental stress causing physiological, psychological and behavioral changes in humans. The aim of the present study was to determinate the effect of chronic noise at moderate intensities on both glandular and cardiac function and oxidative status. Our problem comes from working conditions in call centers where operators are responsible for making simple and repetitive tasks. One wishes to ascertain the effects of moderate sound levels on rats exposed to the same noise levels during similar periods to those experienced by call center operators. Male Wistar rats were exposed to 70 and 85 dB(A) to an octave-band noise (8-16 kHz) 6 h/day for 3 month. Corticosterone levels, oxidative status and functional exploration of adrenal and thyroid glands and cardiac tissue were determined. Exposure to long-term noise for different intensities (70 and 85 dB(A)) resulted in increased corticosterone levels, affected various parameters of the endocrine glands and cardiac function. Markers of oxidative stress (catalase, superoxide dismutase and lipid peroxidation) were increased. These results imply that long-term exposure to noise even at moderate levels may enhance physiological function related to neuroendocrine modulation and oxidative imbalance. In these data, the physiological changes occur during the different sounds suggests the concept of allostatic load or homeostatic response of the body.

Date seeds alleviate behavioural and neuronal complications of metabolic syndrome in rats.

Unhealthy dietary habits can play a crucial role in metabolic damages, promoting alteration of neural functions through the lifespan. Recently, dietary change has been perceived as the first line intervention in prevention and/or treatment of metabolic damages and related diseases. In this context, our study was designed to assess the eventual therapeutic effect of date seeds administration on memory and learning and on neuronal markers in a rat Metabolic Syndrome model. For this purpose, 32 adult male Wistar rats were fed with standard diet or high-fat high-sugar diet during ten weeks. After this, 16 rats were sacrified and the remaining rats received an oral administration of 300 mg of date seeds/kg of body weight during four supplementary weeks. Before sacrifice, we evaluate cognitive performances by the Barnes maze test. Afterwards, neuronal, astrocytic, microtubular and oxidative markers were investigated by immunoblotting methods. In Metabolic syndrome rats, results showed impairment of spatial memory and histological alterations. We identified neuronal damages in hippocampus, marked by a decrease of NeuN and an increase of GFAP and pTau396. Finally, we recorded an increase in protein oxidation and lipid peroxidation, respectively identified by an up-regulation of protein carbonyls and 4-HNe. Interestingly, date seeds administration improved these behavioural, histological, neuronal and oxidative damages highlighting the neuroprotective effect of this natural compound. Liquid Chromatography-Mass Spectrometry (LC-MS) identified, in date seeds, protocatechuic acid, caffeoylshikimic acid and vanillic acid, that could potentially prevent the progression of neurodegenerative diseases, acting through their antioxidant properties.

In utero and lactational exposure to low-dose genistein-vinclozolin mixture affects the development and growth factor mRNA expression of the submandibular salivary gland in immature female rats.

It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures.