Phycocyanin alleviates alcohol-induced testicular injury in male Wistar rats.

OBJECTIVE: Given the noteworthy implications of alcohol consumption and its association with male infertility, there has been a notable focus on investigating natural alternatives to mitigate its adverse effects. Thus, this study was conducted to assess the potential protective effect of phycocyanin extract derived from the blue algae Arthrospira (Spirulina) platensis against ethanol-induced oxidative stress, disturbances in testicular morphology, and alterations in sperm production. METHODS: Male rats were divided into four groups (five rats each): the control group received a saline solution, the ethanol exposed group (EtOH) was subjected to intraperitoneal injections of 10 mL/kg of ethanol solution at a concentration of 38% (v/v), the phycocyanin alone treated group (P) received oral administration of phycocyanin at a dosage of 50 mg/kg, and the phycocyanin-cotreated group (PE) was given oral phycocyanin followed by ethanol injections. All treatments were administered over a period of 14 days. RESULTS: Our findings demonstrated that ethanol exposure induced reproductive toxicity, characterized by reduced sperm production and viability, alterations in testicular weight and morphology, increased lipid peroxidation levels, and elevated oxidative enzyme activity. In addition, the ethanol-intoxicated group showed perturbations in serum biochemical parameters. However, the simultaneous exposure to ethanol and phycocyanin exhibited a counteractive effect against ethanol toxicity. CONCLUSION: The results showed that supplementation of phycocyanin prevented oxidative and testicular morphological damage-induced by ethanol and maintained normal sperm production, and viability.

Antidiarrheal and antioxidant activities of Ajuga iva (L.) leave extract.

We studied the effect of Ajuga iva leaves extract (AIE) on the intestinal absorption, motricity and its antioxidant capacity against diarrhea. Wistar rats were divided and received either: castor oil (CO), CO and loperamide or CO and different doses of AIE. AIE prevented dose-dependently CO-induced diarrhea. AIE at 800 mg/kg showed inhibition efficiency on defecation and diarrhea. The pro-oxidant effect of the CO in the small intestine was inhibited significantly in presence of AIE: increasing glutathione peroxidase (GPx) activity and lowering oxygen free radicals (OH°, O2°-), carbonyl protein and malondialdehyde (MDA) levels. However, co-administration of AIE in castor oil-exposed groups significantly increased the intestinal contents of calcium and magnesium. AIE exhibits significant anti-diarrheal activity, related in part to its antioxidant properties. Our investigation also provides experimental evidence for the traditional use of this medicinal plant in the treatment of diarrhea.

Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in adipose tissue of women from Grand Tunis and their association with demographic factors and dietary habits.

Dichlorodiphenyl trichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB) and polychloronated biphenyls (PCBs) were measured in 25 woman adipose tissues collected in 2016 from Grand Tunis, Tunisia. p,p'-DDE, p,p'-DDT, HCB and ß-HCH were the dominant organochlorine pesticides (OCPs) in decreasing order in all samples. The total OCP levels varied from 79 to 343 ng g-1 lipid with a median value of 189 ng g-1 lipid and DDTs contributed approximately 88% to sum OCP. The ratio of p,p'-DDT/p,p'-DDE across all samples is below one, which suggests mainly historic exposure but may indicate some recent exposure to the banned pesticide. The median concentration of PCBs was 109 ng g-1 lipid and ranged between 27 and 204 ng g-1 lipid. PCB-153, PCB-180, PCB-138 and PCB-170 were the most abundant congeners, which contributed about 78% of the total PCBs. Spearman analysis showed that dominant organochlorine compounds (OCs) are highly positive correlated except for PCB-28/31, indicating that women from Tunis are exposed via similar routes. Inhalation exposure could be a possible pathway for the uptake of the less chlorinated congeners. We found positive and statistically significant association with subjects age for HCB (r = 0.517; p = 0.009) and PCBs (r = 0.65; p = 0.001) levels and a weak age-dependent accumulation was found for HCHs (r = 0.375; p = 0.065) and DDTs (r = 0.388; p = 0.056). The concentrations of OC subgroups were not associated with BMI, parity and residence. No association was observed between fish, red/white meat, milk and dairy products consumption and levels of HCB, HCHs and PCBs. DDTs levels were significantly correlated only with milk (p = 0.048) and milk products (p = 0.047) intake.

Effects of testosterone replacement on lipid profile, hepatotoxicity, oxidative stress, and cognitive performance in castrated wistar rats.

OBJECTIVE: Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. METHODS: Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. CONTROL GROUP: non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. RESULTS: Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. CONCLUSIONS: Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.

Effects of PACAP-38 and an analog, acetyl-[Ala15, Ala20] PACAP-38-propylamide, on memory consolidation in the detection of spatial novelty task in rats.

PACAP-38 (P38) is a pleiotropic peptide that exerts multiple peripheral and central actions, including neurotrophic, neuroprotective and anti-inflammatory actions. Previous studies have suggested an improvement of memory in rats that have received a single systemic injection of P38. In a therapeutic perspective, we used an analog, acetyl-[Ala15, Ala20]PACAP-38-propylamide (ALG), to improve both stability and affinity for PAC1 receptors vs. endogen PACAP. We investigated the effect of P38 and ALG on memory consolidation using a spatial novelty detection (SND) task in which rats had to memorize a configuration of objects to identify that, during a test session, a familiar object has been moved to a new location. Rats received an intravenous injection of P38 or ALG after the last training session. In Experiment 1, P38 (30 µg/kg) improved spatial memory consolidation allowing detection of novelty vs. saline injection. In Experiment 2, we confirmed this effect and showed that P38 restored the performance similar to what was found using non-injected rats. This suggests that, contrary to ALG, P38 exerted a promesiant rather than an anxiety-related effect whereas ALG did not show similar action. We also examined whether P38 effect involved an interaction with NR2B-containing NMDA receptors (NMDARs) by administrating ifenprodil (IFE; a selective NR2B-containing NMDAR antagonist) alone or in combination with P38 or ALG. The results suggested that P38 action on memory involved NR2B-containing NMDARs. Lastly, brain-derived neutrophic factor (BDNF) modulation appeared to be not related to the behavioral performance in the SND task. Overall, the results indicate that P38 exerted a beneficial effect on memory consolidation in a non-associative task, whereas ALG did not have this action.

Comparison of the effects of PACAP-38 and its analog, acetyl-[Ala15, Ala20] PACAP-38-propylamide, on spatial memory, post-learning BDNF expression and oxidative stress in rat.

We compared the effects of single intraveinous injection of pituitary adenylate cyclase-activating polypeptide-38 (P38) to those of its analog, acetyl-[Ala15, Ala20]PACAP-38-propylamide (P38-alg) on spatial memory in the Morris water maze (MWM) using a weak massed-learning procedure, post-training brain derived neurotrophic factor (BDNF) and post-training oxidative stress biomarker assays in male Wistar rats. Acquisition of the MWM task following P38 (30 µg/kg) and P38-alg (30 µg/kg) treatments was similar to control group (Saline: 0.9% NaCl) and there was no interaction between treatments and performance. However, in the probe test, P38-treated group showed a specific interest for the target quadrant whereas the two other groups exhibited less focused place searching behavior. Moreover, P38 had an anxiogenic effect as measured by the distribution of swimming at the periphery of the pool. The swimming test resulted in a decrease in BDNF contents in the hippocampus. P38 but not P38-alg treatment restored BDNF expression. In terms of oxidative stress, both P38 and P38-alg treatments had antioxidative effects. The activity of antioxidative enzymes in the neocortex was increased. However only P38 reduced the levels of carbonylated proteins (CP). These data show that P38 and P38-alg have different behavioral and neurobiological effects. Thus, P38-alg and other analogs with specific functional profiles, inducing beneficial central effects (e.g. neuroprotection) while minimizing undesired peripheral effects may be useful for potential therapeutical use.

Hepatotoxicity of vanadyl sulfate in nondiabetic and streptozotocin-induced diabetic rats.

This study examined the effects of vanadyl sulfate (VOSO4) on the livers of nondiabetic and streptozotocin-induced diabetic rats. Rats were divided into 6 groups. Groups 1, 2, and 3 consisted of nondiabetic rats that were, respectively, control animals or those receiving an intraperitoneal (i.p.) injection of either 5 or 10 mg·kg-1 (i.p.) VOSO4 for 30 days. Groups 4, 5, and 6 consisted of diabetic animals that were, respectively, control animals or those treated with 5 or 10 mg·kg-1 (i.p.) VOSO4 for 30 days. Results showed that VOSO4 reduced body mass in nondiabetic rats, whereas it increased body mass in diabetic groups. Plasma transaminases (aspartate aminotransferase, alanine aminotransferase), lactate dehydrogenase, and alkaline phosphatase activities and malondialdehyde levels were increased, while liver catalase and superoxide dismutase activities were profoundly decreased in diabetic animals in comparison with enzyme activities in the nondiabetic group. Rats in the diabetic group also showed notable oxidative damage to the liver. Treatment of diabetic rats with VOSO4 decreased the hepatotoxic markers, significantly restored the activities of antioxidant enzymes, and attenuated histopathological changes in liver tissue. In nondiabetic rats, VOSO4 treatment increased most of the hepatotoxic markers, reduced antioxidant enzyme activities, and induced pronounced oxidative damage in liver tissue. These data suggest that treatment with VOSO4 exerts toxic effects in healthy animals and significantly prevents liver oxidative damage in streptozotocin-induced diabetic rats, but without total safety. Further studies are needed to clarify its mechanism of action.

A combination of NMR and liquid chromatography to characterize the protective effects of Rhus tripartita extracts on ethanol-induced toxicity and inflammation on intestinal cells.

Consumption of ethanol may have severe effects on human organs and tissues and lead to acute and chronic inflammation of internal organs. The present study aims at investigating the potential protective effects of three different extracts prepared from the leaves, root, and stem of the sumac, Rhus tripartita, against ethanol-induced toxicity and inflammation using intestinal cells as a cell culture system, in vitro model of the intestinal mucosa. The results showed an induction of cytotoxicity by ethanol, which was partially reversed by co-administration of the plant extracts. As part of investigating the cellular response and the mechanism of toxicity, the role of reduced thiols and glutathione-S-transferases were assessed. In addition, intestinal cells were artificially imposed to an inflammation state and the anti-inflammatory effect of the extracts was estimated by determination of interleukin-8. Finally, a detailed characterization of the contents of the three plant extracts by high resolution Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry revealed significant differences in their chemical compositions.

Variability of antioxidant and biological activities of Rhus tripartitum related to phenolic compounds.

Rhus species are known in traditional medicine for their therapeutic virtue and their extracts showed numerous important properties including antimalarial, antimicrobial, antiviral, and hypoglycemic and anticonvulsant activities. Rhus tripartitum (Ucria) is a medicinal plant widely used in Tunisia folk medicine against chronic diarrhea and gastric ulcer. This study was designed to examine in vitro and ex vivo antioxidant, anti-inflammatory and anticancer activities of four extracts of Rhus tripartitum root cortex with increasing solvent polarity (hexane, dichloromethane, methanol and water). HPLC was used to identify and quantify phenolic compounds in Rhus extract. Water extract showed the highest antioxidant activity using oxygen radical absorbance capacity (ORAC method) with 8.95 ± 0.47 µmol Trolox/mg and a cell based-assay with 0.28 ± 0.12 µmol Trolox/mg as compared to the other fractions. Moreover, methanol extract displayed the strongest anti-cancer activity against human lung carcinoma (A-549) and colon adenocarcinoma cell lines (DLD-1) with an IC50 value of 60.69 ± 2.58 and 39.83 ± 4.56 µg/ml (resazurin test) and 44.52 ± 5.96 and 55.65 ± 6.00 µg/ml (hoechst test), respectively. Besides, the highest anti-inflammatory activity, inhibiting nitric oxide (NO) release, was exhibited by dichloromethane extract with 31.5 % at 160 µg/ml in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The HPLC analysis showed that catechol and kaempferol were the major phenolics. These data suggest the richness of all fractions of Ucria root on interesting bioactive molecules with different polarity and confirm the known traditional therapeutics virtues of this species for the treatment of dysentery, diarrhea and gastric ulcer.

Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

Organochlorine pesticides and polychlorinated biphenyls in human adipose tissue from northern Tunisia: Current extent of contamination and contributions of socio-demographic characteristics and dietary habits.

The aims of the present study were to investigate the current exposure levels of persistent organochlorine compounds (OCs) in adipose tissues intraoperatively collected from 40 patients over 20 years undergoing non-cancer-related surgery residing in Northern region of Tunisia (Bizerte), which constitutes an exemplary case, and examined association between levels of contamination and both socio-demographic characteristics and dietary habits. Concentration of hexachlorobenzene (HCB), hexachlorocyclohexane isomers (α-HCH, ß-HCH, γ-HCH and δ-HCH), dichlorodiphenyltrichloroethane isomers (p,p'-DDT and o,p'-DDT) and metabolites (p,p'-DDE, o,p'-DDE, p,p'-DDD and o,p'-DDD) and 12 polychlorinated biphenyls (PCBs) congeners were measured using capillary gas chromatography with electron capture detector. Overall, residue levels of OCs followed the decreasing order of DDTs > PCBs > HCB > HCHs. DDTs levels ranged from 74.49 to 1834.76ngg-1 lipid and contributing to more than 90% to the sum of organochlorine pesticides (OCPs). p,p'-DDE was the most abundant in all samples and the p,p'-DDT/p,p'-DDE ratio (range between 1.85% and 58.45%) suggesting recent and ongoing exposure to banned commercial DDT products. PCB concentrations varied from 29.27 to 322.58ngg-1 lipid and PCB-180, PCB-153 and PCB-138 were the dominant congeners accounting for 70% of total PCBs. We did not find significant correlations between OC exposure levels and sex, parity, habitat areas and smoking habits. In females, the adipose tissue concentrations of DDTs, HCB and PCB-118 were positively correlated with age. There was statistically significant relationship between body mass index (BMI) changes and the adipose tissue levels of HCB and HCHs. No association was found between OCPs levels and dietary factors. However, our study suggests that fish consumption may be an important contributor of PCBs adipose tissue content of PCBs in Tunisian people. The presented work is highly significant, being the first study pointing out the chronic exposure to OCs in Bizerte.

p,p'-DDT induces testicular oxidative stress-induced apoptosis in adult rats.

BACKGROUND: The 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) is a known persistent organic pollutant and male reproductive toxicant. The present study is designed to test the hypothesis that oxidative stress mediates p,p'-DDT-induced apoptosis in testis. METHODS: Male Wistar rats received an intraperitoneal (ip) injection of the pesticide at doses of 50 and 100mg/kg for 10 consecutive days. The oxidative stress was evaluated by biomarkers such lipid peroxidation (LPO) and metallothioneins (MTs) levels. Antioxidant enzymes activities was assessed by determination of superoxide dismutase (SOD), catalase (CAT) and hydrogen peroxide (H2O2) production. In addition, glutathione-dependent enzymes and reducing power in testis was evaluated by glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione S-transferase (GST) activities and reduced and oxidized glutathione (GSH - GSSG) levels. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis and the apoptotic index was assessed through the TUNEL assay. RESULTS: After 10 days of treatment, an increase in LPO level and H2O2 production occurred, while MTs level, SOD and CAT activities were decreased. Also, the Gpx, GR, GST, and GSH activities were decreased, whereas GSSG activity was increased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of DDT-exposed rats. In addition, the apoptotic index was significantly increased in testis of DDT-treated rats. CONCLUSIONS: These results clearly suggest that DDT sub-acute treatment causes oxidative stress in rat testis leading to apoptosis.

Hepatoprotective activity of Rhus oxyacantha root cortex extract against DDT-induced liver injury in rats.

The present investigation aimed to study the antioxidant activity and hepatoprotective effects of ethyl acetate extract of R. oxyacantha root cortex (RE) against DDT-induced liver injury in male rats. The RE exhibited high total phenolic, flavonoid and condensed tannins contents. The antioxidant activity in vitro systems showed a significant potent free radical scavenging activity of the extract. The HPLC finger print of R. oxyacantha active extract showed the presence of five phenolic compounds with higher amounts of catechol and gallic acid. The in vivo results showed that a single intraperitoneal administration of DDT enhanced levels of hepatic markers (ALT, AST and LDH) in serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a significant induction of SOD and GPx, metallothioneins (MTs) and a concomitant decrease of non protein thiols (NPSH) in liver. However, pretreatment of rats with RE at a dose of 150 and 300mg/kg body weight significantly lowered serum transaminases and LDH in treated rats. A significant reduction in hepatic thiobarbituric reactive substances and a decrease in antioxidant enzymes activities and hepatic MTs levels by treatment with plant extract against DDT, were observed. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of RE with the two doses used. These results strongly suggest that treatment with ethyl acetate extract normalizes various biochemical parameters and protects the liver against DDT-induced oxidative damage in rats and thus help in evaluation of traditional claim on this plant.

Mechanisms of chromium hexavalent-induced apoptosis in rat testes.

Hexavalent chromium (CrVI)-containing compounds, present in industrial settings and in the environment, are known as carcinogens and mutagens. The present study is designed to test the hypothesis that oxidative stress mediates CrVI-induced apoptosis in testis. Male Wistar rats received an intraperitoneal injection of potassium dichromate at doses of 1 and 2 mg kg-1. Superoxide anion production was assessed by the determination of the reduction of cytochrome c and iodonitrotetrazolium, lipid peroxidation (LPO), metallothioneins (MTs), and catalase (CAT) activity. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis was detected by toluidine blue staining. The expression of Bax and Bcl-2 proteins (Pts) was also investigated. After 15 days of treatment, an increase of LPO and MT levels occurred, while CAT activity was decreased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of Cr-exposed rats. Bax Pt expression was induced in spermatogonia and spermatocytes cells of CrVI-treated rats. In contrast, Bcl-2 Pt was occasionally observed in germ cells of CrVI-exposed rats. These results clearly suggest that CrVI subacute treatment causes oxidative stress in rat testis leading to apoptosis.

Effects of oral administration of 2,4-dichlorophenoxyacetic acid (2,4-D) on reproductive parameters in male Wistar rats.

The 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide in agriculture as a selective herbicide. It has been shown to produce a wide range of adverse effects on the health of both animals and humans from embryotoxicity and teratogenicity to neurotoxicity. In the present study, we have examined the effect of 2,4-D on male reproductive function of rats. Male Wistar rats received daily by force-feeding 100 or 200 mg of 2,4-D/kg body weight for 30 consecutive days. Rats exposed to 100 and 200 mg of 2,4-D/kg showed a significant decrease in body weights only after 24 days of treatment and in relative weights of testis, seminal vesicles and prostate at killing day, when compared with controls. Moreover, a decrease in testosterone and an increase in FSH and LH serum levels were detected in treated rats. Besides, exposure to this herbicide induced pronounced testicular histological alterations with enlarged intracellular spaces, tissue loosening and dramatic loss of gametes in the lumen of the seminiferous tubules. In addition, a decreased motility and a number of epididymal spermatozoa with an increased sperm abnormality rate were found in treated rats in comparison with control. With the highest dose, histological observations of seminal vesicles indicated a considerable decrease of secretions in the lumen, a thinness of the muscle layer surrounding the epithelium with branched mucosal crypts and reduced luminal space. In prostate, the heights of the cells decreased while acinar lumen were enlarged and they lost the typical invaginations. Our results suggest that a subacute treatment of 2,4-D promotes reproductive system toxicity.

Evaluation of the anti-diarrheal activity of the hydromethanolic root extract of Rhus tripartita (Ucria) (Anacardiacae).

INTRODUCTION: Rhus tripartita (Anacardiacae) is a plant which is traditionally used for the treatment of ulcer and diarrhea in Tunisia. However, the scientific basis for this usage has not been well established. The core aim of the present study is to evaluate the antidiarrheal activity of Rhus tripartita root methanolic extract (RRE). MATERIAL AND METHODS: The antidiarrheal activity of RRE oral doses (50, 100, 200 and 300mg/kg) was evaluated using the castor oil-induced diarrhea, the intestinal fluid emptying method and the normal intestinal transit test. The antibacterial activity was tested against four pathogenic bacteria using two methods. The RRE was also phytochemical studied. RESULTS: Diarrhea experiments showed a protective effect of the RRE which produced a significant (p<0.05) and dose-dependent reduction of all the diarrhea parameters. It delayed the onset of diarrhea, produced a significant decrease in the frequency of defecation and the diarrhea score severity and decreased the volume of intestinal fluid induced by castor oil as well as the propulsion intestinal transit. The effect of the extract at the highest dose (300mg/kg) was similar to that of loperamide, the standard anti-diarrheal drug (10mg/kg). The anti-bacterial activity test showed that RRE exhibited a great inhibition activity against four pathogenic bacteria strains (Esherichia coli, Salmonella typhimurium, Salmonella argenosa, Staphylococcus aureus). Oral administration of the extract up to 3g/kg did not produce any acute toxicity in rats. The preliminary phytochemical screening of the RRE revealed the presence of flavonoids, tannins, and polyphenols. CONCLUSION: Results showed that RRE at 300mg/kg possesses the highest anti-diarrheal activity possibly mediated by the inhibitory effects on gastrointestinal propulsion and intestinal fluid accumulation.

Evaluation of oxidative response and tissular damage in rat lungs exposed to silica-coated gold nanoparticles under static magnetic fields.

The purpose of our study was the evaluation of toxicological effects of silica-coated gold nanoparticles (GNPs) and static magnetic fields (SMFs; 128 mT) exposure in rat lungs. Animals received a single injection of GNPs (1,100 µg/kg, 100 nm, intraperitoneally) and were exposed to SMFs, over 14 days (1 h/day). Results showed that GNPs treatment induced a hyperplasia of bronchus-associated lymphoid tissue. Fluorescence microscopy images showed that red fluorescence signal was detected in rat lungs after 2 weeks from the single injection of GNPs. Oxidative response study showed that GNPs exposure increased malondialdehyde level and decreased CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in rat lungs. Furthermore, the histopathological study showed that combined effects of GNPs and SMFs led to more tissular damages in rat lungs in comparison with GNPs-treated rats. Interestingly, intensity of red fluorescence signal was enhanced after exposure to SMFs indicating a higher accumulation of GNPs in rat lungs under magnetic environment. Moreover, rats coexposed to GNPs and SMFs showed an increased malondialdehyde level, a fall of CuZn-superoxide dismutase, catalase, and glutathione peroxidase activities in comparison with GNPs-treated group. Hence, SMFs exposure increased the accumulation of GNPs in rat lungs and led to more toxic effects of these nanocomplexes.

Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats.

The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP), we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m(3)/h) for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM) for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC) and cytokines (IL-1α and TNF-α) in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.

Chemical composition, antioxidant properties and hepatoprotective effects of chamomile (Matricaria recutita L.) decoction extract against alcohol-induced oxidative stress in rat.

The present study assessed the chemical composition, antioxidant properties, and hepatoprotective effects of subacute pre-treatment with chamomile (Matricaria recutita L.) decoction extract (CDE) against ethanol (EtOH)-induced oxidative stress in rats. The colorimetric analysis demonstrated that the CDE is rich in total polyphenols, total flavonoids and condensed tannins, and exhibited an important in vitro antioxidant activity. The use of LC/MS technique allowed us to identify 10 phenolic compounds in CDE. We found that CDE pretreatment, in vivo, protected against EtOH-induced liver injury evident by plasma transaminases activity and preservation of the hepatic tissue structure. The CDE counteracted EtOH-induced liver lipoperoxidation, preserved thiol -SH groups and prevented the depletion of antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). We also showed that acute alcohol administration increased tissue and plasma hydrogen peroxide (H(2)O(2)), calcium and free iron levels. More importantly, CDE pre-treatment reversed all EtOH-induced disturbances in intracellular mediators. In conclusion, our data suggest that CDE exerted a potential hepatoprotective effect against EtOH-induced oxidative stress in rat, at least in part, by negatively regulating Fenton reaction components such as H(2)O(2) and free iron, which are known to lead to cytotoxicity mediated by intracellular calcium deregulation.

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.