Embryotoxicity and fetotoxicity following intraperitoneal administrations of hexavalent chromium to pregnant rats

Heavy metals are omnipresent in the environment, and industrial use has greatly increased their presence in soil, water and air. Their inevitable transfer to the human food chain remains an important environmental issue as many heavy metals cause a range of toxic effects, including developmental toxicity. Administration of chromium VI (1 and 2 mg/kg as potassium dichromate) through intraperitoneal (i.p.) injection during organogenesis (days 6 to 15 of gestation) in rats revealed embryo- and fetotoxic effects. Reduced fetal weight, retarded fetal development, number of fetuses per mother and high incidences of dead fetuses and resorptions in treated mothers were also observed. Gross morphological abnormalities, such as displayed form of edema, facial defect, lack of tail, hypotrophy, severs subdermal haemorrhage patches and hypotrophy of placenta were observed in fetuses after chromium VI-treated mothers. A skeletal development of fetuses presented an incomplete ossification in nasal, cranium, abdominal or caudal bones in rats treated with 1 mg/kg of chromium, whereas rats treated with 2 mg/kg showed ossification and absence of the sacral vertebrae compared with the control. At a higher dose of chromium, histological changes were found in fetuses with atrophy of theirs vital organs. Placental histological observations revealed a pronounced morphological alteration, with atrophy of decidual cells, a degenerated of chorionic villi and hypertrophy of blood lacuna. The present study suggests a risk to the developing embryo when the mother is exposed to a high concentration of chromium VI during organogenesi

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 activi- ties. 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, di-chloromethane, methanol and water). HPLC was used to identify and quantify phenolic compounds in Rhus ex- tract. 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 les with different polarity and confirm the known traditional therapeutics virtues of this species for the treatment of dysentery, diarrhea and gastric ulcer

Pituitary Adenylate Cyclase Activating Peptide (1-38) and its analog (Acetyl-[Ala15, Ala20] PACAP 38-polyamide) reverse methacholine airway hyperresponsiveness in rats

O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (pThe aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (

Cactus (Opuntia ficus indica f. inermis) fruit juice protects against ethanol-induced hematological and biochemical damages in rats

A putative beneficial effect of Opuntia ficus indica f. inermis prickly pear juice (OFIj) was tested on ethanol-induced hematological and biochemical damages in rats. Our results show that chronic ethanol treatment (300 mg/100 g body weight for 90 days) of Wistar rats (group 2) significantly reduced red blood cells (RBC) and platelet (Plt) counts, hemoglobin (Hb) content, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) whereas white blood cells (WBC) counts and the mean corpuscular volume (MCV) significantly increased as compared to the controls rats treated with same distilled water (group 1). In addition, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) as well as urea, creatinine, cholesterol and triglycerides concentrations significantly increased in ethanol-fed rats. Furthermore, serum, hepatic and renal lipid peroxidation levels were also increased in animals given ethanol compared to the controls. In alcoholic rats co-treated with 4 ml OFIj / 100 g b.w. (group 3), all the above cited parameters were maintained to near-normal values. In group 4 only 4 ml OFIj / 100 g b.w. was given, no changed parameters was shown. Therefore, OFIj appeared to be a promising agent for protection against ethanol toxicity.Key words: Opuntia, alcohol, blood, liver, kidney, toxicity

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

Abstract 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

Vanadyl Sulfate Treatment Stimulates Proliferation and Regeneration of Beta Cells in Pancreatic Islets

We examined the effects of vanadium sulfate (VOSO4) treatment at 5 and 10 mg/kg for 30 days on endocrine pancreas activity and histology in nondiabetic and STZ-induced diabetic rats. In diabetic group, blood glucose levels significantly increased while insulinemia level markedly decreased. At the end of treatment, VOSO4 at a dose of 10 mg/Kg normalized blood glucose level in diabetic group, restored insulinemia, and significantly improved insulin sensitivity. VOSO4 also increased in a dose-dependent manner the number of insulin immunopositive beta cells in pancreatic islets of nondiabetic rats. Furthermore, in the STZ-diabetic group, the decrease in the number of insulin immunopositive beta cells was corrected to reach the control level mainly with the higher dose of vanadium. Therefore, VOSO4 treatment normalized plasma glucose and insulin levels and improved insulin sensitivity in STZ-experimental diabetes and induced beta cells proliferation and/or regeneration in normal or diabetic rats

Protective effects of edible Rhus tripartita (Ucria) stem extract against ethanol-induced gastric ulcer in rats

Rhus tripartita is a plant which is traditionally used for the treatment of ulcer and diarrhea in Tunisia. The aim of the study is to evaluate the antiulcer activity of methanol extract of Rhus tripartita stem (RSE). The phytochemical analysis of RSE was performed. Fasted rats treated with 80% ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with RSE at different doses (200, 400 and 800 mg/kg body weight (BW)) and ranitidine (100 mg/kg) and distilled water were used as a positive and negative control respectively. The results showed that the pre-treatment with RSE decreased significantly the ethanol gastric ulcer index value and preserved the integrity of the gastric mucosa by preventing the mucosal ulceration caused by ethanol. The RSE prevented alcohol-induced decrease in stomach antioxidant enzyme activities such as catalase, glutathione peroxidase and superoxide dismutase. Total reduced glutathione and malondialdehyde tissue contents were also reversed in RSE-pretreated rats when compared with the negative control grou

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/m3/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

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