Subchronic administration of Parastar insecticide induced behavioral changes and impaired motor coordination in male Wistar rats.

Parastar is an insecticide formulation of lambda-cyhalothrin and imidacloprid largely used for crop protection in North West Region of Cameroon. In the present study, we evaluated the behavioral activities and motor function of Wistar male rats after subchronic treatment with the pesticide formulation. To this end, three groups of adult rats were administered Parastar at doses 1.25, 2.49 and 6.23 mg/kg, respectively, for 35 days. A control group was included and received distilled water. At the end of the treatment, the animals were submitted to behavioral and functional tests (open field test, elevated plus maze test, light-dark box test, forced swimming test, tail suspension test, beam-walking test, grid suspension test and wire hang test) for estimation of anxiety, exploration, depression and motor coordination. Results revealed that Parastar, at the higher doses tested, 2.49 and 6.23 mg/kg, induced anxiogenic-like pattern behavior in rats in all behavioral assays including open field test (total distance moved, total lines crossed, frequency and total time in center square were all reduced), elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze), and light-dark box (the dark box duration increased, while light box duration time and frequency of transition between dark and light box decreased). Treatment with 2.49 and 6.23 mg/kg Parastar increased the immobility time of animals in both forced swimming test and tail suspension test. The insecticide induced decrease in the distance traveled, foot slip and number of turns of animals in the beam walking test. Parastar also decreased the animal suspension time in both grid suspension grip-strength test and the wire hang test. Taken altogether, these results suggest that subchronic administration of Parastar at the doses of 2.49 and 6.23 mg/kg induced anxiety-like and depressive-like behavior as well as impaired motor coordination and muscle strength in male rats.

Khaya grandifoliola C.DC: a potential source of active ingredients against hepatitis C virus in vitro.

In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 µg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 µM daclatasvir or 1 µM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1'-(oxydiethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1'-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle.

A prominent role of Hepatitis D Virus in liver cancers documented in Central Africa.

BACKGROUND: Hepatocellular Carcinoma (HCC) is one of the commonest cancers in Central Africa, a region with the unusual peculiarity to be hyperendemic for infections with Hepatitis B, C and D viruses. However, data estimating the respective proportions of HCC cases attributable to these viruses are still limited in this area. The current study was undertaken to determine the role of these viruses in HCC compared to non-HCC Cameroonian patients. METHODS: A case-control study was conducted in the Gastroenterology Unit of Central Hospital of Yaounde in collaboration with Centre Pasteur of Cameroon. Blood samples of all HCC cases (n = 88) and matched control individuals without known liver disease (n = 85) were tested for serological markers of Hepatitis B, C and D viral infections using commercially available enzyme immune-assay kits. Hepatitis B and C viral loads were quantified for positive patients by real-time PCR using commercial kits. RESULTS: The mean age was 46.0 ± 18 and 42.1 ± 16 years old for HCC-patients and controls, respectively for a 2.3 Male/Female sex ratio. The prevalence of hepatitis B surface antigen, antibody to HCV and antibody to HDV were significantly higher in HCC patients (65.90, 20.26 and 26 % respectively) than in control patients (9.23, 4.62 and 1 %) (P < 2.5 10-5). The risk factors analysis showed that both HBV and HCV infections were strongly associated with HCC development in Cameroon with crude odds ratios of 15.98 (95 % CI 6.19-41.25) and 7.33 (95 % CI 2.09-25.77), respectively. Furthermore, the risk of developing HCC increased even more significantly in case of HBV and HDV co-infections with the odd ratio of 29.3 (95 % CI, 4.1-1231). HBV-DNA level was significantly higher in HBsAg-positive HCC-patients than in HBsAg-positive controls with (6.3 Log IU/mL and 5.7 Log IU/mL) respectively (P < 0.05). CONCLUSION: HBV and HCV infections are the mains factors of HCC development in Cameroon. Our results show that patients co-infected with HDV are at very high risk to develop HCC. An active surveillance program of patients and, foremost, an easier access to antivirals and primary prevention measures are crucial steps to reduce the incidence of HCC in this country. Due to the lack of truly efficient antiviral therapy, the fate of HDV-infected patients remains, however, particularly worrying.

Active chemical fractions of stem bark extract of Khaya grandifoliola C.DC and Entada africana Guill. et Perr. synergistically protect primary rat hepatocytes against paracetamol-induced damage.

BACKGROUND: Khaya grandifoliola (Meliaceae) and Entada africana (Fabaceae) are traditionally used in Bamun (a western tribe of Cameroon) traditional medicine for the treatment of liver related diseases. In this study, the synergistic hepatoprotective effect of respective active fractions of the plants were investigated against paracetamol-induced toxicity in primary cultures of rat hepatocytes. METHODS: Paracetamol conferred hepatocyte toxicity, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) activities, malondialdehyde (MDA) and glutathione (GSH) content assays. The crude extracts were fractionated by flash chromatography and fractions were tested for hepato-(protective and curative) activities. The most active fractions of both plants were tested individually, and in combination based on their respective half effective concentration (EC50). RESULTS: The methylene chloride/methanol fractions of K. grandifoliola (75:25 v/v) (KgF25) and E. africana (90:10 v/v) (EaF10) were found to be the most hepato-protective with EC50 values of 10.30 ± 1.66 µg/ml and 13.47 ± 2.06 µg/ml respectively, comparable with that of silymarin (13.71 ± 3.87 µg/ml). These fractions and their combination significantly (P <0.05) improved cell viability, inhibited ALT leakage and MDA formation, and restored cellular CAT, SOD activities and GSH content. The combination was more effective in restoring biochemical parameters with coefficients of drugs interaction (CDI) less than 1. CONCLUSION: These findings demonstrate that the active fractions have synergistic action in the protection of rat hepatocytes against paracetamol-induced damage and suggest that their hepatoprotective properties may be maximized by using them in combination.

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.

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

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.

Assessment of the digestibility, growth performance, hematological and serum biochemical profile of Bandjock Local Pigs (BLP) and Duroc X Large White pigs (DLW).

The study aimed to assess the digestibility, growth performance, and selected biochemical and hematological parameters of Bandjock Local pigs (BLP) and Duroc X Large White pigs (DLW). We hypothesize that the use of local ingredients in diet formulation associated to improved rearing conditions, enhance the growth performance, digestibility, biochemical and hematological parameters of BLP. The trial involved dividing twenty-four eight-week-old weaner pigs into two groups. Each group was randomly assigned to separate pig units. Animal management and feeding were consistent between both groups. The trial lasted for 120 days during which the growth performance, the digestibility of ingested nutrients, and biochemical and hematological parameters were evaluated. The results indicate that DLW pigs registered a weight gain (46.56±5.19 kg) significantly higher than BLP pigs (34.02), with a statistically similar feed conversion ratio. Except for albumin which was significantly higher in DLW and urea in BLP, there were no significant differences (p > 0.05) in total protein, cholesterol, globulin, triglycerides, creatinine, AST, and ALT as well as hematological parameters between the breeds. However, the exotic DLW had a relatively high mean blood platelets and white blood cell concentration. Although the fecal nitrogen was higher in BLP and the urinary nitrogen was lower in the DLW, there were significant differences (p < 0.05) for urine, fecal, and total excreted nitrogen in both breeds. The lowest scores in nutrient digestibility were recorded with BLP compared to DWL, except for crude fibers. The results of this study demonstrated that using diet formulated with local ingredients and improved rearing conditions, Cameroonian local indigenous pigs have a better productivity compared to exotic breeds. It suggests that efforts should be made by authorities to promote and valorize the rearing of indigenous pigs in complement to exotic pig breeds in view of strengthening the Cameroonian pig industry.

Exposure of Male Farmers and Nonfarmers to Neonicotinoid Pesticides in the South-West and Littoral Regions of Cameroon: A Comparative Study.

Pesticides, especially the newly developed neonicotinoids, are increasingly used in many countries around the world, including Cameroon, to control pests involved in crop destruction or disease transmission. Unfortunately, the pesticides also pose tremendous environmental problems because a predominant amount of their residues enter environmental matrices to affect other nontargeted species including humans. This therefore calls for continuous biomonitoring of these insecticides in human populations. The present study sought to assess the neonicotinoid insecticide exposures in two agrarian regions of Cameroon, the South-West region and Littoral region. The study involved 188 men, including 125 farmers and 63 nonfarmers. Spot urine samples were obtained from these subjects and subjected to liquid chromatographic-tandem mass spectrometric analysis for concentrations of neonicotinoid compounds, including acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, nitenpyram, thiamethoxam, and N-dm-acetamiprid. Neonicotinoid compounds were detected in all study participants, and residues of all the screened pesticides were detected among participants. N-dm-Acetamiprid and imidacloprid were the most prevalent among the subjects (100.0% and 93.1%, respectively), whereas nitenpyram was less common (3.2%). The median values of imidacloprid and total urinary neonicotinoid concentrations were elevated among farmers (0.258 vs. 0.126 µg/L and 0.829 vs. 0.312 µg/L, respectively). Altogether the findings showed that both the farmer and nonfarmer study populations of Cameroon were exposed to multiple residues of neonicotinoids, with relatively higher levels of pesticides generally recorded among farmers. Although exposure levels of the neonicotinoids were generally lower than their respective reference doses, these results warrant further research on the health risk evaluation of multiple residues of the pesticides and reinforcement of control measures to minimize the exposure risks, especially among farmers. Environ Toxicol Chem 2024;43:952-964. © 2024 SETAC.

Entada africana fraction CH2Cl2/MEOH 5% inhibits inducible nitric oxide synthase and pro-inflammatory cytokines gene expression induced by lipopolysaccharide in microglia.

BACKGROUND: Inflammatory response in the CNS mediated by microglia cells play an important role in host defense and is implicated in the pathology of neurodegenerative diseases. We investigated the capacity of Entada africana to protect microglia from inflammatory insults by exploring the effect of the CH2Cl2/MEOH 5% fraction (Ea5) on pro-inflammatory cytokines mRNA expression. Finally, we studied the effect of Ea5 on the inhibition of p38 MAPK Kinase. The results were compared to those obtained with Baicalin, a well reported anti-inflammatory flavonoid. METHODS: Barks from E. africana were harvested in 2010, in the west region of Cameroon. A crude extract was prepared using CH2Cl2/MEOH 1:1 V/V. The crude extract obtained was further fractionated by flash chromatography. A mouse microglia cell line (N9) was stimulated by LPS with or without different concentrations of Baicalin and Ea5. The release of NO was evaluated using the Griess method. The expression of pro-inflammatory cytokines mRNA (TNFα, IL-1ß, IL-6) and iNOS/NO were measured by RT- PCR. The inhibition of p38 MAPK Kinase was assessed using ELISA. RESULTS: We found that Ea5, as well as Baicalin inhibited LPS-induced NO production in a dose dependent manner. Ea5 was most active in term of NO inhibition (87.07%), in comparison to Baicalin (70.85%). The expression of TNFα, IL-1ß, IL-6 and iNOS was strongly suppressed by Ea5 in microglia. Ea5 also inhibited the activity of p38MAPK Kinase, up to 30% for the concentrations tested, whereas a prominent inhibition was obtained with Baicalin. CONCLUSION: These results suggest that E. africana may contain promising compounds useful for the treatment of diseases cause by over-activation of microglia such as Alzheimer disease and other neurological diseases.

Determination of multiple mycotoxins levels in poultry feeds from Cameroon.

For the first time in Cameroon, this paper reports on multiple mycotoxins occurrences in poultry feeds. Twenty feed samples collected from different poultry farms were analyzed for 320 fungal metabolites by liquid chromatography electrospray ionization tandem mass spectrometry. Results showed feeds contamination by 68 metabolites including 18 mycotoxins/metabolites currently regulated in the European Union such as fumonisins B1 (FB1), B2, and B3; deoxynevalenol (DON); and beta-zearalenol recovered in all samples. FB1 reported highest FB mean level of 468 (range 16-1930) microg kg(-1). Levels of DON and ZEN were mostly concentrated in feeds from western-highlands conversely for FBs and aflatoxins concentrations in Yaounde. Aflatoxin B1 mean level of 40 microg kg(-1) exceeded the worldwide permitted limit for aflatoxins in feed and generally inversely proportional to weight gain in chicken.

Toxic Potential of Crude Extract From Cassava Cortex Containing Scopoletin and Cyanide on Wistar Rats and Broilers.

The present work aimed to evaluate acute and sub-acute toxicity of cortex cassava crude extract containing scopoletin and cyanide. The limit test method of OECD at 2000 mg/kg was used to determine the LD50 of the crude extract in female Wistar rats, and the sub-acute toxicity was conducted in broilers by incorporating their feed with the cortex powder at 2 mg, 4 mg and 8 mg of powder per 100 g of standard food, corresponding to MIC, 2MIC and 4MIC: those concentrations, respectively, corresponded to .07 µg, .14 µg and .28 µg of scopoletin and 2.8 µg, 5.6 µg and 11.2 µg of cyanide. An oral LD50 greater than 2000 mg/kg was obtained, and the effective antifungal dose was non-toxic. No changes were observed in the rate of biochemical parameters and relative weight of the liver, kidneys and brain of broilers. Any damages were not observed after the histopathological exams of these organs regardless the diet considered, compared to the control group. All results ranging from efficacy and safety of cassava cortex extract containing scopoletin and cyanide allowed us to consider it as biopesticide for staple food preservation against post-harvest losses.

Comparative assessment of hepatoprotective properties of Artesunate and flavonoids from Artemisia annua on acetaminophen and carbon tetrachloride-induced cytotoxicity in primary mice hepatocytes.

Background: Artesunate (ART) is a semi-synthetized molecule from Artemisinin, an active compound isolated from the medicinal plant Artemisia annua, widely used for the treatment of malaria. Previous studies reported that ART may exert a dual effect on the liver. Accordingly, this study investigated the potential protective action of ART against Acetaminophen (APAP) and Carbon tetrachloride (CCl4)-induced hepatotoxicity in primary mice hepatocytes, in comparison to that of flavonoid extracted from A. annua (FAA). In addition, the antioxidant properties of FAA were also assessed. Methods: The antioxidant activities of FAA and Ascorbic acid (ASC) (0.01-100 µg/mL) were assessed through inhibition of lipid peroxidation, reduction of ferric and phosphomolydenum, and hydroxyl and DPPH radicals scavenging assays. The hepatoprotective effects of FAA and ART (0.1-100 µg/mL) were evaluated against APAP (11 mM) or CCl4 (4 mM) induced oxidative damage in primary mouse hepatocytes. Biochemical parameters associated with hepatotoxicity assessed include cell viability, cell membrane integrity, cellular glutathione, and antioxidant enzyme activities. Results: The obtained finding revealed FAA displayed a remarkable antioxidant activities as evidenced by the low IC50/EC50 values (3.85-19.32 µg/mL), comparable to that of ASC (3.26-18.04 µg/mL). When tested at 10 µg/mL, both FAA and ART significantly (p˂0.05) preserved cell viability, inhibited alanine aminotransferase leakage and lipid membrane peroxidation, and restored superoxide dismutase and catalase activities and glutathione content induced by APAP or CCl4 in a similar way as Silymarin. However, ART showed a significant (p˂0.05) cytotoxic effect on hepatocytes at 100 and 1000 µg/mL and did not confer obvious protection at 100 µg/mL. Conclusion: Overall, our data demonstrated that ART harms mice hepatocytes at high concentration while conferring relative protection against APAP and CCl4-hepatotoxicity at low concentration. In contrast, FAA effectively protects liver cells without cytotoxicity effect, event at 100 µg/mL. Accordingly, ART should be given to the patient only under a medical prescription.

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 17ß- hydroxysteroid dehydrogenase (17HSD3) and induction of aromatase (CYP19).

Hydro-ethanolic extract of Khaya grandifoliola attenuates heavy metals-induced hepato-renal injury in rats by reducing oxidative stress and metals-bioaccumulation.

People living in developing countries are exposed to hepato-renal injuries induced by heavy metals like lead (Pb), cadmium (Cd), and mercury (Hg) since drinking water supplied is often polluted with a high concentration of those metals. Accordingly, it is necessary to search for antidotes against heavy metals poisoning. Hence, medicinal plants bearing anti-hepatotoxic properties represent a credible option; and such plant is Khaya grandifoliola. However, there is a paucity of knowledge regarding its protective effect on heavy metals-induced hepato-renal toxicity. Thus, this study was designed to assess the protective effect of the hydro-ethanolic stem bark extract of K. grandifoliola (HKG) against hepato-renal injuries induced by chronic consumption of drinking water containing high contents of Pb, Cd, and Hg; in addition to the investigation of the chemical antioxidant properties of HKG. For the antioxidant assays, HKG was tested as a potential inhibitor of lipid peroxidation, reducer of ferric and phosphomolybdenum, and scavenger of hydroxyl and 2,2-Diphenyl-Picryl-Hydrazyl radicals. Its protective effects were evaluated by daily co-treating rats with heavy metals solution (10 mL/kg b.w) containing 0.9, 0.58, and 1.13 ppm respectively for Pb, Cd and Hg and HKG (25 or 100 mg/kg b.w) for five consecutive months; and biochemical parameters associated to liver and kidneys functions, oxidative stress and metals bioaccumulation were assessed. HKG displayed a strong antioxidant capacity (IC50/EC50 range 3.95-17.17 µg/mL) correlated to its polyphenols content and comparable to that of Ascorbic acid. Serum levels of alkaline phosphatase, alanine/aspartate aminotransferase, and creatinine; renal and hepatic content of Cd and Pb, malondialdehyde and glutathione, activities of superoxide dismutase and catalase showed the protective effect of HKG, further evidenced by histopathological analysis. Taking together, these results demonstrated that HKG alleviates heavy metals-induced hepato-renal injuries in rats by reducing oxidative stress and metals-bioaccumulation.

Effects of the methanol extract of Basella alba L (Basellaceae) on steroid production in Leydig cells.

In this study, Leydig cells were purified from 70 day-old Sprague Dawley male rats and incubated with 10 and 100 µg/mL of methanol extract of Basella alba (MEBa) for 4 hours followed by the evaluation of cell viability, steroid (testosterone and estradiol) production, and the level of aromatase mRNA. Results showed that MEBa did not affect Leydig cell viability. At the concentration of 10 µg/mL, MEBa significantly stimulated testosterone and estradiol production (p < 0.01 and p < 0.03, respectively), and enhanced aromatase mRNA level (p < 0.04). These observations suggest that MEBa directly stimulated testosterone, estradiol and aromatase mRNA levels in isolated Leydig cells.

Inhibitory activity of limonoids from Khaya grandifoliola C.DC (Meliaceae) against hepatitis C virus infection in vitro.

OBJECTIVE: A fraction from Khaya grandifoliola has recently been shown to inhibit hepatitis C virus (HCV) infection and three limonoids (17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and 7-deacetoxy-7R-hydroxygedunin) were purified from this fraction. The present study aimed at assessing the inhibitory effect of these limonoids on HCV using cell-culture derived HCV (HCVcc) system. MATERIALS AND METHODS: Cytotoxic effects of the limonoids on Huh7.5 cells were assessed by MTT assay. Huh7.5 cells were transfected with RNA transcripts of the plasmid Jc1/GLuc2a, carrying a Gaussia luciferase reporter gene to rescue the HCVcc particles which were used to infect naïve cells in the presence or absence of the studied limonoids during 72 hr. Infection and replication rates were monitored by luciferase reporter assay and immunofluorescence assay (IFA) while cellular gene expression was analyzed by western blot, respectively. RESULTS: The limonoids inhibited HCV infection mostly by targeting entry and replication stage. Their inhibitory effect on entry step, comparable to that of anti-CD81 antibody, was related to the blocking of CD81 receptor. In the replication step, the limonoids decreased the expression of NS5B similar to danoprevir. These compounds also significantly decreased but up-regulated the expression of Class-III phosphatidylinositol 4-kinase alpha and 2',5'-oligoadenylate synthase-3, respectively. CONCLUSION: The present findings suggest that limonoids from K. grandifoliola are potential anti-HCV agents and may offer an advantage in the treatment of HCV infection.

Occupational use of agrochemicals results in inhibited cholinesterase activity and altered reproductive hormone levels in male farmers from Buea, Cameroon.

The efficiency of agro pesticides and fertilizers in eliminating pests and scaling up crop yield has motivated farmers to increase their use. Unfortunately, health hazards caused on farmers by these agrochemicals are of growing concern, though not well elucidated. In order to evaluate the effects of occupational exposure to agrochemicals on some key parameters of male farmers' health in Buea Subdivision, Cameroon, a total of 101 men, including 62 farmers using the agrochemicals and a reference population of 39 men not involved in occupational utilization of the agrochemicals, were interviewed on use of protective equipment, exposure symptoms and reproductive health status. Thereafter, serum cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] activities, total antioxidant capacity and reproductive hormones [follicle-stimulating hormone (FSH), luteinizing hormone and testosterone] were assessed. Results revealed that farmers mainly used insecticides followed by fungicides, herbicides and fertilizers, but with inadequate protective measures. The use of agrochemicals resulted in several exposure symptoms including weakness, itches, burning sensation, headache, sneezing, coughing and vomiting, as well as decrease in serum AChE activity when compared to the reference population. The agrochemicals impacted negatively on the farmers' reproductive health as evidenced by increased FSH levels. Taken altogether, these results suggested that exposure to agrochemicals adversely affects farmers' health. Therefore, there is a need to further sensitize the farmers on the use of protective equipment to mitigate the exposure and resulting health hazards.

Natural compounds flavonoids as modulators of inflammasomes in chronic diseases.

The use of dietary or medicinal plant based natural compounds to disease treatment has become a unique trend in clinical research. Flavonoids, a group of polyphenolic compounds have drawn significant attention due to their modulatory effects on inflammasomes associated with the initiation and progression of chronic disorders including metabolic, neurodegenerative diseases and cancer. In this article, the role of most commonly studied natural flavonoids with their disease-specific impact via inflammasomes as a potential molecular target has been described. Since the role of inflammation is evident in multiple diseases, flavonoids may serve as a promising tool in drug discovery for the intervention of chronic diseases by manipulating the status of inflammation via inflammasome targeting.

Inhibition of CYP2E1 and activation of Nrf2 signaling pathways by a fraction from Entada africana alleviate carbon tetrachloride-induced hepatotoxicity.

Entada africana is used in non-conventional medicine for the management of liver ailments. A fraction, designated EaF10 (methylene chloride/methanol 90:10, v/v) with promising hepatoprotective activity has been isolated. Since the mechanisms underlying EaF10 hepatoprotective action remain unknown, this study was undertaken to investigate the anti-hepatotoxic mechanism of the fraction against carbon tetrachloride (CCl4)-induced hepatotoxicity and its antioxidant properties. Antioxidant activities of EaF10 were assessed through four chemical antioxidant assays and its anti-hepatotoxic effect evaluated in vivo and in vitro by post-treatment (25 or 100 mg/Kg) or co-treatment (6.25-100 µg/mL) in CCl4-intoxicated mice and normal human liver cells line L-02 hepatocytes respectively; and biochemical and molecular parameters assessed respectively by spectrophotometry, and by quantitative real-time polymerase chain reaction and western blot analysis. EaF10 exhibited strong antioxidant activities correlated with its polyphenol content. Serum levels of alanine/aspartate aminotransferase (AST/ALT) and nitrite oxide, liver contents of glutathione (GSH) protein carbonylation and malondialdehyde (MDA), liver activities of catalase (CAT), glutathione-S-transferase (GST) and superoxide dismutase (SOD) and cell viability showed the anti-hepatotoxic effect of EaF10, supported by histopathological observations. The fraction decreased the protein level of Cytochrome P450 2E1 (CYP2E1) and Kelch-like ECH-associated protein-1 (Keap-1), induced nuclear translocation of Nuclear factor-erythroid 2-related factor-2 (Nrf2) coupled to an increase of the mRNA levels of CAT, SOD1 and GST in CCl4-intoxicated L-02 hepatocytes. These findings evidenced that the studied plant fraction possesses a strong antioxidant capacity and prevents CCl4-induced hepatotoxicity, likely through inhibition of CYP2E1 and activation of the Nrf2 signaling pathway.

Evaluation of the Effects of Agro Pesticides Use on Liver and Kidney Function in Farmers from Buea, Cameroon.

Agro pesticides are increasingly used worldwide to increase crop production. However, health hazards resulting from human exposure to these chemicals, especially from agricultural areas of developing countries have been a growing concern. The objective of this study was to evaluate the impact of occupational exposure to agro pesticides on the health of farmers in the Buea subdivision, which is one of the major agrarian areas in Cameroon. The study was transversal and involved 90 participants including 58 farmers using pesticides and a reference population of 32 men not involved in occupational use of agro pesticides. The participants were interviewed on agro pesticide use and their health status. Thereafter, blood samples were collected from the participants and used for the assessment of biochemical markers of the liver (alanine aminotransferase and aspartate aminotransferase) and the kidney (creatinine and uric acid) function. Results revealed that farmers frequently used insecticides, fungicides, and herbicides in their farming activities. Farmers reported several acute health symptoms related to pesticides use with the common ones being skin rash, eye irritation, and face burn. When compared to the reference population, the farmers showed significantly elevated (p < 0.01) alanine aminotransferase activity. However, other parameters investigated were not affected significantly. These results suggested that farmers were exposed to 3 different classes of agro pesticides, which induced eye and skin affections. Pesticides exposure resulted in alterations of the liver function hence the increased serum alanine aminotransferase activity. Therefore, there is a need to sensitize the farmers on toxicity and liver alteration potential of agro pesticides and the importance of appropriate protective equipment that may minimize exposure.