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.

Effects of lead, cadmium, copper and zinc levels on the male reproductive function.

This study aimed to investigate the effects of heavy metals on measures of male fertility. One hundred and two infertile men with occupational exposure and thirty fertile men were included in this study. Blood and urinary levels of lead, cadmium, zinc and copper were measured by atomic absorption spectrophotometry. Semen parameters and a motile sperm organelle morphology examination were also performed. Measures of hormonal levels, oxidation-reduction potential, DNA fragmentation index and chromatin condensation were assessed for all participants. Heavy metals levels, oxidative stress and DNA quality were significantly higher in the infertile group compared to controls. FSH and testosterone levels were lower in the infertile group. A urinary cadmium level was positively associated with abnormal sperm morphology (r = .225, p < .05). Normal morphology was inversely correlated with the duration of the exposure (r = -.227, p = .022). The blood lead level was positively related to the level of testosterone (r = .223, p = .031). Cadmium and lead blood levels were positively correlated with the level of chromatin decondensation (r = .528, p < .001; r = .280, p = .017). Our study showed that occupational exposure to heavy metals is very harmful to reproductive health. DNA quality and oxidative stress investigations must be recommended for reprotoxic exposed patients prior to in vitro fertilisation treatment.

Evaluation of the status and the relationship between essential and toxic elements in the hair of occupationally exposed workers.

Lead poisoning is a common disease in lead-acid battery manufacturing industries. Workers can be also exposed to various toxic elements present as contaminants or used as catalysts to enhance batteries' performances. In the present study, levels of essential and toxic elements and their relationship were assessed by analyzing scalp hair samples of 52 workers in a Pb battery manufacturing plant. The impact of some confounding factors on hair mineral contents was also investigated. For comparative purposes, nonoccupationally exposed subjects were selected as controls. All elements were determined by triple quadrupole ICP-MS. The results indicated significantly higher levels of Pb, Sb, As, and Cd in the hair of workers when compared to controls (p < 0.01). The Spearman correlation test revealed significant correlations between Pb/Cr, Pb/Mn, Pb/Ni, Pb/As, Pb/Se, Pb/Sb, Hg/As, Hg/Sn, Hg/Sb, Sb/Cr, Sb/As, Sb/Se, Sb/Cd, Sb/Sn, Sn/Cr, Sn/As, Sn/Cd, Cd/As, Se/Ni, As/Cr, Ni/Cr, Ni/Mn, and Mn/Cr in the hair of workers and Pb/Cr, Pb/Mn, Pb/Ni, Pb/Cd, Mn/Ni, Mn/Cd, Cd/Ni, As/Ni, Sn/Ni, Sb/Sn, and Hg/Sn in the hair of controls. Multiple linear regression analysis revealed linear dependence including Cr = f(Pb, Ni, Sb), Mn = f(Ni, Sb), Ni = f(Mn, Cr, -Cd) (Cd was negatively correlated, ß < 0), As = f(Sn, Sb, Hg), Se = f(Ni); Sn = f(As), Sb = f(As, Mn, -Hg, Sn, Se, -Ni) (Hg and Ni were negatively correlated), Hg = f(As, -Sb, Sn) (Sb was negatively correlated), and Pb = f(Cr). The result of this study can be very useful to explain the interactions between elements or for comparison studies when establishing reference ranges or monitoring elements in workplaces.

Toxic effects of methamidophos on paraoxonase 1 activity and on rat kidney and liver and ameliorating effects of alpha-tocopherol.

The role of alpha-tocopherol on nephrotoxicity and hepatotoxicity induced by methamidophos (MT) was investigated in wistar rats. Animals were given via gavage, for four weeks, a low dose of MT (MT1), a high dose of MT (MT2), vitamin E (200 mg/kg of bw) or both MT2 plus vitamin E (Vit E) and control group was given distillate water. MT treatment resulted in a significant decrease in the body weight of MT2-treated group. Moreover, MT-treated groups had significantly lower butyrylcholinesterase (p < 0.01) and paraoxonase 1 (PON1) activities compared with the control group (p < 0.05). However, MT2-treated group had significantly higher alkaline phosphatase activity compared with untreated rats (p < 0.05). Both MT-treated groups had significantly higher urea (p < 0.01) and uric acid levels (p < 0.05) compared with the control group. However, significant low uric acid level (p < 0.05) was noted in MT2 plus vit E-treated rats compared with MT2-treated group. Histopathological changes in organ tissues were observed in both MT-treated groups and MT2 plus vit E-treated rats. However, the damage was reduced in MT2 plus vit E-treated rats. Therefore, this study deduces that alpha-tocopherol administration may ameliorate the adverse effects of subacute exposure to MT on rat liver and kidney and this antioxidant can protect PON1 from oxidative stress induced by this organophosphorus pesticide. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 842-854, 2016.

Tunisian Artemisia campestris L.: a potential therapeutic agent against myeloma - phytochemical and pharmacological insights.

BACKGROUND: Artemisia campestris L. (AC) leaves are widely recognized for their importance in traditional medicine. Despite the considerable amount of research conducted on this plant overworld, the chemical composition and the biological activity of the leaves grown in Tunisia remains poorly investigated. In this study of AC, a successive extraction method was employed (hexane, ethyl acetate and methanol) to investigate its bioactive constituents by LC-MS analysis, and their antioxidant, antibacterial, antifungal, and anticancer activities. RESULTS: Data analysis revealed diverse compound profiles in AC extracts. Methanolic and ethyl acetate extracts exhibited higher polyphenolic content and antioxidant activities, while Hexane showed superior phytosterol extraction. Ethyl acetate extract displayed potent antibacterial activity against multi-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, all extracts demonstrated, for the first time, robust antifungal efficacy against Aspergillus flavus and Aspergillus niger. Cytotoxicity assays revealed the significant impact of methanolic and ethyl acetate extracts on metastatic breast cancer and multiple myeloma, examined for the first time in our study. Moreover, further analysis on multiple myeloma cells highlighted that the ethyl acetate extract induced apoptotic and necrotic cell death and resulted in an S phase cell cycle blockage, underscoring its therapeutic potential. CONCLUSIONS: This investigation uncovers novel findings in Tunisian AC, notably the identification of lupeol, oleanolic acid, ursolic acid, stigmasterol and ß-sitosterol. The study sheds light on the promising role of AC extracts in therapeutic interventions and underscores the need for continued research to harness its full potential in medicine and pharmaceutical development.

Sewage analysis as an alternative tool for assessing drug of abuse and new psychoactive substances in Tunisia.

Many studies attest to the pollution of wastewaters by organic molecules including drug of abuse (DAs) residues and new psychoactive substances (NPS) at trace levels. The occurrence of these emerging micropollutants in influent wastewaters (IWW) from three Tunisian Wastewater Treatment Plants (WWTPs) was assessed. Influent wastewater composite samples (24 h) were collected over 7 consecutive days in November 2019. The determination and quantification of 11 drug of abuse or their metabolites was performed by the application of an optimized multi-residue method liquid chromatography tandem mass spectrometry (LC-MS/MS). MDMA, THC and the cocaine metabolite benzoyl ecgonine were the most detected substances across the three investigated sewage plants. A new wastewater-based epidemiology (WBE) approach was applied in this study to estimate illicit drug consumption. This innovative approach was used to calculate and to assess collective drug consumption of illicit drug at a community level, based on the concentration of selected illicit substances and their major metabolites in influent wastewater. The average MDMA consumption found in the selected cities ranged between 35,8-1531,1 mg day- 1/1000 inhabitants and increased during the weekends. Cocaine consumption varied from 24.5 to 179.8 mg day- 1/1000 inhabitants. Complementary qualitative investigation of new psychoactive substances was monitored for the first time for an African country, examining the occurrence of 33 NPS in wastewaters samples. Out of 33 totals screened NPS across all sampling sites, 16 were tentatively identified with this approach. The 16 detected NPS covered most of the representative and used molecules of different NPS classes; including synthetic opioids, synthetic cathinones, amphetamines derivatives and synthetic cannabinoids.

Factors influencing plasma butyrylcholinesterase activity in agricultural workers.

We studied the influence of some factors on plasma butyrylcholinesterase activity (BChE) and we assessed the health status of agricultural workers and looked for the effects of chronic exposure to pesticides, in the aim to determinate factors that must be considered for interpretation of BChE, for occupational monitoring of workers exposed to pesticides. The study was carried out in 110 workers from the Sahel region of Tunisia exposed to pesticides and in 97 controls. All individuals have undergone clinical examination. BChE activity was measured by spectrophotometric method. The mean of BChE activity of workers was significantly lower than that of control group (P < 0.001). Among the 44% of farmworkers with at least one neurologic or neuropsychic symptom, 29% had BChE activity lower than 6000 IU/L. Headache was observed in 20% of workers. Ancientness of exposure equal to 10 years or more, last exposure dates back to 60 days or less, exposure for 2 days or more per week, exposure exceeding 150 h per year and to organophosphorus-carbamates mixture were implicated in significant decreases of BChE activity and can be considered as risk factors of cholinergic toxic effects. Thus, BChE activity is a useful indicator to monitor workers chronically exposed to pesticides. However, it should be accompanied by periodical health examination, taking into account risk factors, for an early identification of workers at increased risk.

Lower paraoxonase 1 activity in Tunisian bipolar I patients.

BACKGROUND: The purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population. PATIENTS AND METHODS: Our study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL), low-density lipoprotein cholesterol (c-LDL), triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (Apo)A1, ApoB and lipoprotein (a) (Lp(a)) were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific). RESULTS: Compared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a) level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P < 0.001). The lowest paraoxonase activity was noted in relation to age and body mass index (BMI). Moreover, it was associated with gender but not with smoking and alcohol consumption status. In patients, there was no significant change in paraoxonase activity in relation to illness episodes, whereas the lowest values of this activity were seen in manic patients. In contrast, paraoxonase activity was significantly associated with treatment. Indeed, patients taking lithium had the lowest levels. CONCLUSIONS: Bipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

Simple analytical method for determination of pesticide residues in human serum by liquid chromatography tandem mass spectrometry.

The aim of this study was to develop an analytical method for the determination of residues of organophosphorus and carbamate pesticides which are widely used in Tunisia. This method involves a liquid-liquid extraction procedure followed by liquid chromatography tandem mass spectrometry (LC/MS/MS) for the identification and quantification of compounds. Ionization of molecules was performed by the electrospray mode. Multiple reactions monitoring (MRM) was the acquisition mode used for the monitoring of two MS/MS transitions for each compound. The average recoveries obtained, at three different fortification levels, ranged between 65% and 106% for most of the pesticides studied, except for methamidophos (lower than 25%).The linearity of the method was in the range of 5 to 50 micro g/L with a correlation coefficient from 0.995 to 0.999, depending on the analyte. The estimated limit of detection and limit of quantification were 2 micro g/L and 5 micro g/L, respectively. The precision of the analytical procedure was satisfactory and the coefficients of variation, evaluated at three concentration levels were lower than 15% for most pesticides studied. The application of the method was investigated in a population of agricultural workers chronically exposed to various pesticides some of which, such as carbofuran, carbendazim, methomyl and pirimicarb, were detected in some serum samples.

[Paraoxonase 1 (PON1) activity and lipid parameters in Tunisian smokers]. / Etude de l'activité de la paraoxonase 1 (PON1) et du profil lipidique dans une population de fumeurs tunisiens.

This study aims at examine the effect of cigarettes smoking on paraoxonase 1 (PON1) activity and lipid profile. Our study included 102 smokers aged 35.5 +/- 16.0 years and 98 non-smokers aged 38.5 +/- 21.9 years. Total cholesterol (TC), triacylglycerols (TG), HDL cholesterol (CHDL) and LDL-cholesterol (cLDL) were determined by enzymatic colorimetric methods. ApoA1 and ApoB and Lp(a) were analyzed by immunoturbidimetry on Konélab 30, PON1 activity was measured by a kinetic method. Plasma CT, TG, cLDL, Lp(a) and ApoB/ApoA1 ratio appeared significantly higher in the smokers when compared to nonsmokers, since cHDL levels were lower. In addition, TG values were significantly higher in subjects smoking more than 30 cigarettes/day as compared to those smoking 5-10 cigarettes/day. We noted a significant decrease of PON1 activity in smokers compared to non smokers (94 +/- 104 vs 158 +/- 133 IU/L), with regression of PON1 activity according number of cigarettes/day. In conclusion, hypertriglyceridemia, low levels of cHDL, high levels of ApoB/ApoA1 and significant decrease of PON1 activity confirm the high risk of cardiovascular diseases in smokers.

Biomonitoring chronic lead exposure among battery manufacturing workers in Tunisia.

The aim of the study was the biomonitoring of the chronic exposure to Pb by measuring its levels in blood, urine, and hair of battery workers. Blood lead (BPb), urinary lead (UPb), hair lead (HPb), and urinary δ-aminolevulinic acid (UALA) levels were determined for 52 workers in a battery plant and compared to those of 20 non-occupational exposed subjects (controls). BPb and UPb levels were determined by graphite furnace atomic absorption spectrometry (GFAAS). HPb levels were measured by triple quadrupole ICP-MS and UALA levels were determined using cation exchanger column. The measured levels were significantly higher compared to the controls exceeding the OSHA cutoff values (p < 0.01). The GM mean levels of BPb, UPb, UALA, and HPb of workers were 715 µg L-1, 331 µg L-1, 16.3 mg g-1, and 234 µg g-1, respectively. The GM mean levels of BPb, UPb, UALA, and HPb of controls were 93.6 µg L-1, 36.3 µg L-1, 1.9 mg g-1, and 1.8 µg g-1, respectively. Significant correlations were observed between BPb and UALA (r = 0.630, p = 0.000), UPb and UALA (r = 0.566, p = 0.000), and between BPb and HPb (r = 0.466, p = 0.004). The significant correlation between BPb and HPb suggests the usefulness of hair for assessing occupational exposure particularly when the study area presents medium to high levels of Pb pollution. The association between Pb biomarkers and potential confounding factors revealed significant influence of the occupational factor over smoking and alcohol consumption. The results of this study urge for the reinforcement of the implemented engineering controls and safety measures in order to reduce exposure and to address the health issues related to Pb poisoning.

[Plasma cholinesterase activity in hepatic diseases]. / Étude de l'activité de la cholinestérase plasmatique au cours des atteintes hépatiques.

Plasma cholinesterase activity (ChE) may vary in some pathological circumstances. We studied the changes in activity of this enzyme according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. Our study was performed on 102 patients with different liver diseases and 53 healthy controls. The ChE activity was lower in patients compared to control group (p < 0.0001), and more pronounced in cirrhotic patients compared to those suffering from hepatitis. Elevated activities of AST, ALT, GGT and ALP and bilirubinemia, and decreased albuminemia were noted in patients compared to controls (p < 0.001). Hypoalbuminemia was significantly important in cirrhotic patients compared to those suffering from cholestasis or hepatitis. A correlation between ChE and bilirubin, albumin and serum protein was found in patients with cirrhosis or those with chronic hepatitis. A significantly lower activity of ChE was found in patients with hepatic insufficiency (HI). In case of suspicion of HI, the prescription of ChE activity could guide or confirm the diagnosis of the impairment.

Adverse effects of pesticides on biochemical and haematological parameters in Tunisian agricultural workers.

Biomonitoring of effects in agricultural workers is necessary to assess the individual risk of handling pesticides. In this study, biochemical and haematological parameters were measured to evaluate the effects of exposure to these compounds in agricultural workers. The study was carried out in 110 workers and 97 control subjects. Several haematological and biochemical parameters were analysed. Assessment of haematological parameters revealed that the mean cell volume and haematocrit levels were significantly lower in workers than in controls (P=0.002 and 0.013, respectively), while mean corpuscular haemoglobin concentrations were higher in workers (P<0.001). There was also a significant inhibition of butyrylcholinesterase activity in workers compared with that in controls (P<0.001). Assessment of biochemical parameters further showed significantly higher activities of transferases, lactate dehydrogenase (P<0.001), alkaline phosphatase (ALP) (P=0.006) and creatine kinase (CK) (P<0.015), as well as higher levels of proteins (P<0.001), creatinine (P=0.001) and urea (P=0.001) in workers compared with controls, along with significantly higher uric acid levels (P=0.012). Furthermore, the number of years exposed to pesticides predicted higher activities of alanine aminotransferase, CK, ALP, as well as uric acid levels. Overall, chronic exposure to pesticides appeared to affect several biochemical parameters. These biomarkers seem to be indicative of adverse effects of pesticides in agricultural workers, confirming their use for routine monitoring of effects.

Paraoxonase 1 correlates with butyrylcholinesterase and gamma glutamyl transferase in workers chronically exposed to pesticides.

OBJECTIVES: Agricultural workers chronically exposed to complex mixtures of pesticides are at increased risk of acute and chronic toxicity of these compounds. Enzyme activities are among the biomarkers that may be used to detect the effects of pesticides before adverse clinical health effects occur. The aims of this study were to ascertain the relationships between paraoxonase 1 (PON1) and other serum enzymes and to investigate whether long-term exposure to pesticides affects these relationships in Tunisian agricultural workers. METHODS: The activities of butyrylcholinesterase (BChE), aminotransferases, gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in plasma from workers chronically exposed to pesticides using an Integra 400 plus(TM) system. PON1 activity was measured using konelab 30(TM) system. RESULTS: Significant increases in aminotransferases, CK, LDH and ALP activities were found in workers exposed to pesticides. However, BChE and PON1 activities were decreased significantly in these subjects. In addition, PON1 activity was positively correlated with both BChE and GGT activities in these workers. CONCLUSION: This study suggests that pesticides lead to alteration of serum enzymes and that chronic exposure to pesticides might contribute to explain the positive correlation between PON1 and GGT, perhaps in order to protect BChE and simultaneously induce detoxification of pesticides.