Faustin Pascal Tsagué Manfo

Effects of maneb on testosterone release in male rats.

Maneb (Manganese ethylene-bis-dithiocarbamate) is a widely used fungicide in agriculture. In order to investigate its effect on male reproductive function, rats were intraperitonealy injected with maneb (1 and 4u2009mg/kg) for 9 or 18 days. After 6 and 14 days of treatment, the animals received human chorionic gonadotropin (hCG) via a jugular catheter and blood samples were collected at several intervals subsequent to the challenge. They were thereafter decapitated after 9 or 18 days, and organs (i.e., liver, seminal vesicles, and kidneys) were weighed. Leydig cells prepared from rats after 18 days of treatment were incubated with or without different stimulators or precursors [hCG, A23187, 25-OH-cholesterol (25-OH-C), or androstenedione] for 1 hour, and the media were analyzed for testosterone or pregnenolone. Liver glutathione and thiobarbituric acid reactive substances (TBARS) as well as serum alanine aminotransferase (ALT) activity were also measured. Further, Leydig cells and testicular interstitial cells (TICs) prepared from normal rats were incubated with maneb (3–100 µM) for 1 or 2 hours, and testosterone release was assessed. The results showed that administration of maneb (4u2009mg/kg) for 9 and 18 days did not alter liver function, but resulted in a decrease of basal level of plasma testosterone (Pu2009<u20090.01). In addition, basal testosterone and pregnenolone release by Leydig cells prepared from maneb 18-day treated animals were significantly reduced (Pu2009<u20090.05). However, acute in vitro exposure of TIC or Leydig cells to maneb did not alter their testosterone release. These results suggested that maneb alters testosterone production, at least in part, through inhibition of CYP11A1 activitiy.

Adverse Effects of Bisphenol A on Male Reproductive Function

BPA is a ubiquitous environmental contaminant, resulting mainly from manufacturing,use or disposal of plastics of which it is a component, and the degradation of industrial plastic-related wastes. Growing evidence from research on laboratory animals, wildlife, and humans supports the view that BPA produces an endocrine disrupting effect and adversely affects male reproductive function. To better understand the adverse effects caused by exposure to BPA, we performed an up-to-date literature review on the topic, with particular emphasis on in utero exposure, and associated effects on spermatogenesis, steroidogenesis, and accessory organs.BPA studies on experimental animals show that effects are generally more detrimental during in utero exposure, a critical developmental stage for the embryo. BPA has been found to produce several defects in the embryo, such as feminization of male fetuses, atrophy of the testes and epididymides, increased prostate size, shortening of AGD, disruption of BTB, and alteration of adult sperm parameters (e.g.,sperm count, motility, and density). BPA also affects embryo thyroid development.During the postnatal and pubertal periods and adulthood, BPA affects the hypothalamic-pituitary-testicular axis by modulating hormone (e.g., LH and FSH,androgen and estrogen) synthesis, expression and function of respective receptors(ER, AR). These effects alter sperm parameters. BPA also induces oxidative stress in the testis and epididymis, by inhibiting antioxidant enzymes and stimulating lipid peroxidation. This suggests that employing antioxidants may be a promising strategy to relieve BPA-induced disturbances.Epidemiological studies have also provided data indicating that BPA alters male reproductive function in humans. These investigations revealed that men occupationally exposed to BPA had high blood/urinary BPA levels, and abnormal semen parameters. BPA-exposed men also showed reduced libido and erectile ejaculatory difficulties; moreover, the overall BPA effects on male reproduction appear to be more harmful if exposure occurs in utero. The regulation of BPA and BPA-related products should be reinforced, particularly where exposure during the fetal period can occur. The current TDI for BPA is proposed as 25 and 50 1-1g/kg bwt/day (European Food Safety Authority and Health Canada, respectively). Based on the evidence available, we believe that a TDI value of 5 1-1g/kg bwt/day is more appropriate (the endpoint is modulation of rat testicular function). Certain BPA derivatives are being considered as alternatives to BPA. However, certain of these related products display adverse effects that are similar to those of BPA. These effects should be carefully considered before using them as final alternatives to BPA in plastic production.

Effect of agropesticides use on male reproductive function: A study on farmers in Djutitsa (Cameroon)

This study aimed at investigating the effect of agropesticides on male reproductive function in farmers in Djutitsa (West Cameroon). To this end, 47 farmers in Djutitsa were asked questions on their health status and pesticide use in agriculture. Thereafter, their blood samples were collected for assessment of sex hormones including serum luteinizing hormone (LH), follicle‐stimulating hormone (FSH), androstenedione, testosterone, as well as sex hormone binding globulin (SHBG). Their serum triiodothyronine (T3) and thyroxine (T4) levels were also measured. Thirty seven men not exposed to agropesticides were recruited as control group. Fifty six pesticides containing 25 active substances were currently used by farmers enrolled in our study, and most of their symptoms were related to spread/use of these chemicals. Compared to the control group, there was no significant difference in FSH, LH, SHBG, estradiol, and thyroid hormones (T3 and T4) levels. Farmers had significantly lower serum testosterone (20.93 ± 1.03 nM vs. 24.32 ± 1.32 nM; P < 0.05) and higher androstenedione level (3.83 ± 0.20 nM vs. 2.80 ± 0.15 nM; P < 0.001). Their serum free testosterone as well as bioavailable testosterone were unchanged, while estradiol/testosterone and androstenedione/testosterone ratios were significantly increased (0.45 ± 0.03% vs. 0.33 ± 0.02%; P < 0.01 and 12.26 ± 3.64 vs 19.31 ± 6.82; P < 0.001, respectively). Our results suggest that male farmers of Djutitsa (West Cameroon) are exposed to agropesticides due to improper protective tool, and this exposure may impair their reproductive function through inhibition of testosterone synthesis; probably by inhibition of testicular 17β‐ hydroxysteroid dehydrogenase (17HSD3) and induction of aromatase (CYP19).

Effect of Environmental Contaminants on Mammalian Testis

Exposure of humans and wildlife to pollutants released in the environment is a centre of attention nowadays. Many of these chemicals (generally referred to as environmental pollutants) have been shown to interfere with normal hormonal signalling and biological functions, leading to reproductive disorders or infertility, which has been a matter of concern within the recent decades. The present paper reviews adverse effects of these toxicants on mammalian testes, with emphasis on alteration of steroidogenesis, spermatogenesis, and histopathological effects. From the publications reviewed, it appears that environmental toxicants, especially heavy metals and organic chemicals of synthetic and microbiological origins, disrupt hormone production and action in the mammalian testes. Endocrine disruption leads to disorders of testicular function and thereby compromises the normal phenotypic development of male sexual characteristics, initiation and maintenance of spermatogenesis. The toxicants also induce impairment of testicular cells function, testicular histology, and sperm cells function directly. The release of the toxicants in the environment is still ongoing, despite alarming quantities that already exist in the atmosphere. If appropriate measures are not taken, their impact on the male reproductive function and especially on testicular function will be more serious.

QuEChERS-based method for the determination of carbamate residues in aromatic herbs by UHPLC-MS/MS

A new reliable, fast and highly sensitive method based on ultra-high performance liquid chromatography tandem mass spectrometry has been developed and validated for the determination of 28 carbamates in aromatic herbs. A modified QuEChERS-based method was optimized for the extraction of carbamate residues from a wide variety of fresh herbal products. The proposed method allowed recoveries higher than 72%, achieving quantification limits of 2μgkg(-1), therefore below maximum residue limits established for this type of samples. The combination of QuEChERS with UHPLC-MS/MS introduces a high-throughput methodology for the monitoring of these residues in this type of matrices scarcely explored. The analysis of the real samples revealed that several samples sold in the European Union and in the North West region of Cameroon contain pesticides in concentrations below the maximum residue limits.

Protective effect of Basella alba and Carpolobia alba extracts against maneb-induced male infertility.

Abstract Context: Male infertility is one of the leading causes of social frustration and marginalization, mainly in the developing world. It is attributed to many factors including exposure to agropesticides such as manganese ethylenebis (dithiocarbamate) (maneb), which is one of the most frequently used fungicides in Cameroon. Previous reports support efficiency of some medicinal plants commonly used in Cameroonian folk medicine for the treatment of this disorder. Objective: The present study was aimed at assessing the protective effect of extracts from selected plant species, namely Basella alba L. (Basellaceae) (MEBa) and Carpolobia alba G. Don (Polygalaceae) (AECa), in alleviating the maneb-induced impairment of male reproductive function in Wistar albino rats. Materials and methods: The rats were treated with vehicle, plant extract (MEBa or AECa), maneb and maneb plus plant extract, respectively, and their fertility was assessed. Animals were thereafter sacrificed and organs (liver, kidneys and reproductive organs) were dissected out and weighed. Serum androgens together with alanine aminotransferase, liver glutathione and thiobarbituric acid reactive species (TBARS) were also measured. Results and discussion: From this study, both plant extracts stimulated testosterone and improved fertility. Administration of MEBa plus maneb prevented fertility reduction by maneb and minimized the inhibitory effect of maneb on testosterone levels. AECa also improved fertility of the maneb-exposed rats, though without restoring testosterone levels, and other investigated parameters remained unaffected by different treatments. Conclusion: These findings emphasized the beneficial effects of B. alba and C. alba extracts on male fertility, and suggest their protective effect against maneb-induced toxicity in male reproductive function.

Hepatotoxicity and Hepatoprotective Effects of African Medicinal Plants

Liver diseases constitute a global concern, and available medical treatments have limited efficacy. Herbal medicines have been used for treatment of aliments since ancient times, and some plant extracts and natural compounds find applications as hepatoprotective active principles, while others adversely induced liver toxicity used for treatment of diseases unrelated to liver. Indeed, the liver represents the key “metabolic factory” in the organism and, therefore the most exposed organ to xenobiotics, and may be modulated by any compound irrespective to the purpose of use. This chapter reviews the modulatory effect of African medicinal plants on liver. We identified 47 medicinal plants, with 36 and 11 plants exhibiting hepatoprotective and hepatotoxic effect, respectively. The action mechanisms involved in the hepatotoxicity/hepoprotection by the identified plants are not well elucidated, though modulation of antioxidant system is emphasized. More in-depth research studies are needed to clarify the pathways and molecules involved in their action, and to investigate other unstudied medicinal plants, in order to guarantee their safe use.

Filaricidal activities on Onchocerca ochengi and Loa loa, toxicity and phytochemical screening of extracts of Tragia benthami and Piper umbellatum

BackgroundOnchocerciasis is the world’s second leading infectious cause of blindness. Its control is currently hampered by the lack of a macrofilaricidal drug and by severe adverse events observed when the lone recommended microfilaricide, ivermectin is administered to individuals co-infected with Loa loa. Therefore, there is the need for a safe and effective macrofilaricidal drug that will be able to cure the infection and break transmission cycles, or at least, an alternative microfilaricide that does not kill L. loa microfilariae (mf).MethodsFourteen extracts from two medicinal plants, Tragia benthami and Piper umbellatum were screened in vitro against Onchocerca ochengi parasite and L. loa mf. Activities of extracts on male worms and microfilariae were assessed by motility reduction, while MTT/Formazan assay was used to assess biochemically the death of female worms. Cytotoxicity and acute toxicity of active extracts were tested on monkey kidney cells and Balb/c mice, respectively.ResultsAt 500xa0μg/mL, all extracts showed 100xa0% activity on Onchocerca ochengi males and microfilariae, while 9 showed 100xa0% activity on female worms. The methylene chloride extract of Piper umbellatum leaves was the most active on adult male and female worms (IC50s: 16.63xa0μg/mL and 35.65xa0μg/mL, respectively). The three most active extracts on Onchocerca ochengi females were also highly active on Loa loa microfilariae, with IC50s of 35.12 - 13.9xa0μg/mL. Active extracts were generally more toxic to the worms than to cells and showed no acute toxicity to Balb/c mice. Phytochemical screening revealed the presence of saponins, steroids, tannins and flavanoids in the promising extracts.ConclusionsThese results unfold potential sources of novel anti-Onchocerca lead compounds and validate the traditional use of the plants in onchocerciasis treatment.

Filaricidal properties of Lantana camara and Tamarindus indica extracts, and Lantadene A from L. camara against Onchocerca ochengi and Loa loa

Background Ivermectin is the only drug currently recommended for the treatment of onchocerciasis, the second leading infectious cause of blindness in the world. This drug kills only the first stage larvae—microfilariae (mf) of Onchocerca volvulus and is to be used cautiously in areas where Loa loa is prevalent because of severe adverse events observed with coinfected patients. Methodology/Principal findings This study investigated the anti-filarial activities of two Cameroonian medicinal plants, Lantana camara and Tamarindus indica locally used to treat onchocerciasis. Twelve (12) extracts were prepared and tested in vitro on the bovine model parasite, O. ochengi as well as L. loa mf. Both mf and adult male worm viabilities were assessed by motility scoring, while adult female worm viability was determined biochemically by standard MTT/formazan colorimetry. Cytotoxicity and acute toxicity were determined respectively, in monkey kidney epithelial cells and in BALB/c mice. Pure compounds were isolated by LC/MS using a bio-assay guided strategy. All the extracts showed 100% activity at 500 μg/mL against O. ochengi adult worms and mf. The highest activity against O. ochengi was observed with the hexane extract of L. camara leaves (LCLhex), with IC50 of 35.1 μg/mL for adult females and 3.8 μg/mL for the mf. Interestingly, this extract was more active against O. ochengi mf than L. loa mf. Further studies on the extracts led to the isolation of lantadene A from the methylene chloride extract of L. camara leaves, with IC50s of 7.85 μg/mL for adult males, 10.38 μg/mL for adult females, 10.84 μg/mL for O. ochengi mf and 20.13 μg/mL for L. loa mf. Conclusions/Significance We report for the first time the anti-onchocercal activities of these locally consumed medicinal plants and lantadene A, a potential lead for further development as an onchocerciasis cure.

Characterization of Carbamate Pesticides in Natural Water from Cameroon

ABSTRACT With the increased use of chemicals in agriculture for crop protection and improvement of yield, the contamination of water is currently a serious health concern. This study used solid-phase extraction with ultra-high-performance liquid chromatography–tandem mass spectrometry to evaluate the presence of 23 carbamate pesticides in waters from Cameroon. The separation was achieved in 5.5u2009min using a C18 column (50u2009×u20092.1u2009mm, 1.8u2009µm) with a mobile phase composed of water and methanol each containing 0.01% formic acid. The analytes were determined in positive multiple reaction monitoring mode. The recoveries for fortified water were from 75 to 99%, with relative standard deviations below 13%. The limits of detection ranged from 0.003 to 0.397u2009µgu2009L−1. The reported method is simple, sensitive, and accurate, and is a suitable alternative for routine monitoring of pesticide residues at ultra-trace levels. The analysis revealed the presence of propoxur at a concentration of 0.072u2009µgu2009L−1 in stream water.