Ellagic acid mitigates rotenone-induced damage via modulating mitochondria function in Drosophila melanogaster.

Constant, systematic exposure to rotenone has been utilized in animal models to induce Parkinsonism. Ellagic acid is a polyphenol with anti-inflammatory and antioxidative properties which is found in numerous natural fruits. Here, we investigated the therapeutic effects of ellagic acid in rotenone-induced toxicity in Drosophila melanogaster evaluating their antioxidant and mitoprotective properties. Adult flies were treated with rotenone and ellagic acid through their diet for 7 days, thereafter markers of neurotoxicity (acetylcholinesterase, monoamine oxidase, tyrosine hydroxylase), antioxidant and oxidative stress markers (hydrogen peroxide, nitric oxide, lipid peroxidation, protein carbonyl contents, catalase, total thiol, and nonprotein thiol) was measured. Mitochondrial respiration was also evaluated in the flies. Survival assay was carried out with both genders of the flies, and we observed a significant increase in the survival rate of flies exposed to both rotenone and ellagic acid when compared with the increased mortality rate in the groups exposed to rotenone alone. The impaired locomotion, altered redox status, and enzymes of neurotoxicity induced by rotenone were significantly ameliorated by ellagic acid to levels comparable to the control. In addition, rotenone-induced complex 1 inhibition and altered bioenergetic state were restored upon ellagic acid supplementation. These findings show the beneficial properties of ellagic acid against pesticides induced toxicity.

Jobelyn® extends the life span and improves motor function in Drosophila melanogaster exposed to lipopolysaccharide via augmentation of antioxidant status.

Jobelyn® (JB), a dietary supplement, derived from polyphenol-rich leaf sheath of Sorghum bicolor, has been reported to attenuate sensorimotor deficits and oxidative stress evoked by complete Freund-adjuvant in mice. This present study evaluated its effects on the life span, motor function and changes in oxidative stress parameters as well as acetylcholinesterase activity in Drosophila melanogaster exposed to lipopolysaccharide (LPS). The flies (50 per vial), in 5 replicates were fed with LPS (250 µg/kg diet) alone or in combination with JB (0.25-1.0 mg/kg diet) daily for 7 days. The mortality rate and motor function were evaluated on day 7. The flies were afterwards processed for determination of oxidative stress parameters and acetylcholinesterase activity. The effects of JB (0.25-1.0 mg/g diet) on the longevity of Drosophila was also investigated wherein the flies were monitored daily for mortality throughout their lifespan. The flies exposed to LPS (250 µg/kg diet) had reduced life span and elevated oxidative stress when compared with control. However, JB (0.25 and 1.0 mg/kg diet) improved the motor function and also reduced the mortality rate of the flies exposed to LPS. It also restored the cellular antioxidant status and reduced acetylcholinesterase activity, accumulation of hydrogen peroxide as well as nitric oxide in Drosophila fed with LPS. JB also extended the longevity of the flies relative to control. The findings that JB improves motor function and extended the lifespan of Drosophila flies by boosting the antioxidant status and cholinergic function, suggest it might be helpful in delaying the onset of neuropsychiatric illnesses associated with the aging processes.

Productivity of CNPq Researchers from Different Fields in Biomedical Sciences: The Need for Objective Bibliometric Parameters-A Report from Brazil.

In Brazil, the CNPq (National Council for Scientific and Technological Development) provides grants, funds and fellowships to productive scientists to support their investigations. They are ranked and categorized into four hierarchical levels ranging from PQ 1A (the highest) to PQ 1D (the lowest). Few studies, however, report and analyse scientific productivity in different sub-fields of Biomedical Sciences (BS), e.g., Biochemistry, Pharmacology, Biophysics and Physiology. In fact, systematic comparisons of productivity among the PQ 1 categories within the above sub-fields are lacking in the literature. Here, the scientific productivity of 323 investigators receiving PQ 1 fellowships (A to D levels) in these sub-fields of BS was investigated. The Scopus database was used to compile the total number of articles, citations, h-index values and authorship positions (first-, co- or last-listed author) in the most cited papers by researchers granted CNPq fellowships. We found that researchers from Pharmacology had the best performance for all of the parameters analysed, followed by those in Biochemistry. There was great variability in scientific productivity within the PQ 1A level in all of the sub-fields of BS, but not within the other levels (1B, 1C and 1D). Analysis of the most cited papers of PQ 1(A-D) researchers in Pharmacology revealed that the citations of researchers in the 1C and 1D levels were associated with publications with their senior supervisors, whereas those in the 1B level were less connected with their supervisors in comparison to those in 1A. Taken together, these findings suggest that the scientific performance of PQ 1A researchers in BS is not homogenous. In our opinion, parameters such as the most cited papers without the involvement of Ph.D. and/or post-doctoral supervisors should be used to make decisions regarding any given researcher's fellowship award level.

Curcumin-supplemented diets improve antioxidant enzymes and alter acetylcholinesterase genes expression level in Drosophila melanogaster model.

Curcumin, a bioactive polyphenolic compound in turmeric (Curcuma longa) rhizomes has been shown to exert anti-aging properties with limited scientific basis. Hence, this study sought to examine the antioxidant and anti-cholinesterase activities of curcumin-supplemented diets as well as their molecular effect on superoxide dismutase (SOD) and acetylcholinesterase (AChE) genes expression level associated with lifespan extension in Drosophila melanogaster model. In this experiment, D. melanogaster (both genders) of 1 to 3 days old were fed diets either containing no curcumin (control) or supplemented with curcumin at 0.2 and 1.0 mg/g of diet for 7 days. Subsequently, the survival and locomotor activities were determined. In addition, we evaluated RT-PCR expressions of SOD and AChE mRNA genes. Furthermore, catalase, SOD and AChE activities were determined. Curcumin-supplemented diet improves survival ability but did not affect locomotor activity when compared with the control. In addition, there was a significant increase in SOD and catalase with a concomitant decrease of AChE activities when compared with the control. Furthermore, curcumin-supplemented diets suppress AChE mRNA expression but no alteration on SOD gene expression level was observed when compared with control. In conclusion, our present results suggest that a down-regulation of AChE gene expression with a concomitant decrease of AChE activity as well as improving antioxidant status could be some possible mechanism in which curcumin exert anti-aging potential and increases lifespan of D. melanogaster.

Garcinia kola seed biflavonoid fraction (Kolaviron), increases longevity and attenuates rotenone-induced toxicity in Drosophila melanogaster.

Rotenone, a naturally occurring and commonly used pesticide, has been established as a model for inducing Parkinson's Disease (PD) in rodents. Kolaviron is a biflavonoid complex from Garcinia kola seeds with anti-oxidative and anti-inflammatory properties. Here, we evaluated the ameliorative role of Kolaviron on rotenone-induced toxicity in Drosophila melanogaster. Flies for longevity study were exposed to Kolaviron (100-500mg/kg diet) throughout the lifespan. For biochemical study, Groups A, B and C flies were treated with ethanol (2.0%, control, vehicle), Kolaviron (200mg/kg diet) and rotenone (250µM) respectively. Flies in Group D were co-treated with both rotenone (250µM) and Kolaviron (200mg/kg diet) for 7days. Subsequently, selected markers of antioxidant status, inflammatory and neurotoxicity were evaluated in the flies. The results from longevity experiment showed that Kolaviron (200, 100, 300 and 400mg/kg) extended lifespan of flies by 38.2%, 20.6%, 11.8% and 2.9% respectively. Also, Kolaviron attenuated rotenone-induced inhibition of catalase, glutathione-S-transferase and acetylcholinesterase activities and depletion of total thiols content in flies. Moreover, Kolaviron prevented rotenone-induced increases in hydrogen peroxide and nitric oxide (nitrite and nitrate) levels and improved rotenone-induced decrease in locomotor performance of flies (p<0.05). Overall, this study evidenced for the first time, the lifespan extension property of Kolaviron and its chemoprotective role on rotenone-induced toxicity in D. melanogaster via anti-oxidative and anti-inflammatory mechanisms.

Antioxidant responses driven by Hesperetin and Hesperidin counteract Parkinson's disease-like phenotypes in Drosophila melanogaster.

The study investigated the protective effects of Hesperetin (HSP) and Hesperidin (HSD) on 1 methyl, 4 phenyl, 1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced Parkinsonism in Drosophila melanogaster (D. melanogaster). After a lifespan study to select exposure time and concentrations, flies were co-exposed to MPTP (0.4 mg/g diet), Hesperetin (0.2 and 0.4 mg/g diet), and Hesperidin (0.1 and 0.4 mg/g) for 7 days. In addition to in vivo parameters, we assayed some markers of oxidative stress and antioxidant status (lipid peroxidation, protein carbonylation, thiol content, hydrogen peroxide, and nitrate/nitrite levels, mRNA expression of Keap-1 (Kelch-like ECH associated protein 1), /Nrf2 (Nuclear factor erythroid 2 related factor 2), catalase, and glutathione-S-transferase (GST) activities), and cholinergic (acetyl cholinesterase activity (AChE) and dopaminergic signaling content and the mRNA expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO-like) activity). In addition to increasing the lifespan of flies, we found that both flavonoids counteracted the adverse effects of MPTP on survival, offspring emergence, and climbing ability of flies. Both flavonoids also reduced the oxidative damage on lipids and proteins and reestablished the basal levels of pro-oxidant species and activities of antioxidant enzymes in MPTP-exposed flies. These responses were accompanied by the normalization of the mRNA expression of Keap1/Nrf2 disrupted in flies exposed to MPTP. MPTP exposure also elicited changes in mRNA expression and content of TH as well as in MAO and AChE activity, which were reversed by HST and HSD. By efficiently hindering the oxidative stress in MPTP-exposed flies, our findings support the promising role of Hesperetin and Hesperidin as adjuvant therapy to manage Parkinsonism induced by chemicals such as MPTP.

Evidence of acrylamide-induced behavioral deficit, mitochondrial dysfunction and cell death in Drosophila melanogaster.

Acrylamide (ACR), a ubiquitous compound with diverse route of exposure, has been demonstrated to have detrimental effects on human and animal health. The mechanisms underlying its toxicity is multifaceted and not fully elucidated. This study aims to provide further insight into novel pathways underlying ACR toxicity by leveraging on Drosophila melanogaster as a model organism. The concentrations of acrylamide (25, 50 and 100 mg/kg) and period of exposure (7-days) used in this study was established through a concentration response curve. ACR exposure demonstrably reduced organismal viability, evidenced by decline in survival rate, offspring emergence and deficits in activity, sleep and locomotory behaviors. Using a high-resolution respirometry assay, the role of mitochondria respiratory system in ACR-mediated toxicity in the flies was investigated. Acrylamide caused dysregulation in mitochondrial bioenergetics and respiratory capacity leading to an impaired OXPHOS activity and electron transport, ultimately contributing to the pathological process of ACR-toxicity. Furthermore, ACR exacerbated apoptosis and induced oxidative stress in D. melanogaster. The up-regulation of mRNA transcription of Reaper, Debcl and Dark genes and down-regulation of DIAP1, an ubiquitylation catalyzing enzyme, suggests that ACR promotes apoptosis through disruption of caspase and pro-apoptotic protein ubiquitination and a mitochondria-dependent pathway in Drosophila melanogaster. Conclusively, this study provides valuable insights into the cellular mechanism underlying ACR-mediated toxicity. Additionally, our study reinforces the utility of D. melanogaster as a translational tool for elucidating the complex mechanisms of ACR toxicity.

An assessment of the ameliorative role of hesperidin in Drosophila melanogaster model of cadmium chloride-induced toxicity.

Cadmium chloride (CdCl2) is an important heavy metal widely regarded as an environmental contaminant. Hesperidin, a flavanone glycoside found in citrus fruits, has an established properties against free radicals, apoptosis, and inflammation. The present study investigated the protective actions of hesperidin on CdCl2-induced oxidative damage and inflammation in Drosophila melanogaster. For 7 consecutive days via their diet regimen, the flies were exposed to CdCl2 alone (0.05 mM) or in combination with hesperidin (50 and 100 µM). Exposure to CdCl2 significantly (p < 0.05) increased mortality rate of flies, whereas the survived flies demonstrated significant oxidative toxicity from decreased activities of catalase and Glutathione S-transferase (GST) and Total Thiol (T-SH) and Non-Protein Thiols (NPSH) levels as well as accumulation of Nitric Oxide (NO (nitrite/nitrate)), protein carbonyl and Hydrogen Peroxide (H2O2). However, hesperidin-supplemented diet improved Acetylcholinesterase (AChE) activity, mitochondrial metabolic rate (cell viability), locomotor activity, and amelioration of oxidative damage and lipid peroxidation induced by CdCl2. The hesperidin diet supplement boosted the antioxidant milieu and ameliorated the oxidative damage in the treated flies. Overall, the findings revealed that hesperidin improved antioxidative protective capacity in Drosophila melanogaster model of CdCl2-induced toxicity. This suggests hesperidin as a potential therapeutic agent against oxidative stress disorders due to exposure to CdCl2 and or related toxicants.

Kaempferol counteracts toxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in D. melanogaster: An implication of its mitoprotective activity.

The current study aimed to investigate whether kaempferol (KMP), the major bioactive component of green leafy vegetables, could counteract the toxicity elicited by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Drosophila melanogaster or not. First, we performed a dose-response curve, where adult wild-type flies were fed on diet-containing different concentrations of KMP throughout their lifespan. Afterward, flies were fed on a diet containing MPTP (500 µM) and KMP (20 and 40 µM) for 7 days. The MPTP- fed flies presented a higher mortality rate, lower emergence rate, locomotor deficits, and disruption in circadian rhythm when compared to the control. MPTP exposure induced severe oxidative stress, which was marked by reduction in thiol content, overproduction of reactive species, lipid and protein oxidation, and disruption of enzymes of antioxidant and neurotransmission pathways. MPTP also compromised the mitochondrial dynamics and respiration of flies, affecting the electron transport chain, oxidative phosphorylation, and fusion/fission processes. Besides extending per se the lifespan of flies, KMP counteracted the toxic effects of MPTP on the circadian cycle, survival, climbing, and hatching rates. KMP was also effective in restoring the activities of acetylcholinesterase (AChE) and monoamine oxidase (MAO) enzymes, as well as in normalizing the levels of all oxidant/antioxidant markers disrupted in MPTP-fed flies. Indeed, KMP reestablished the mitochondrial functionality in MPTP- fed flies, restoring the electron transport system linked to mitochondrial complex I and II, and rescuing the mRNA transcription of genes associated with mitochondrial fusion and fission, namely OPA-1 (Optic atrophy 1) and DRP-1 (Dynamin related protein 1). Our results showed the efficacy of KMP in hindering the toxicity induced by MPTP in D. melanogaster and suggest that the mitoprotective action of flavonoid may be boosting its anti-parkinsonism activity in the model. Besides, the study showed that wild-type strains of D. melanogaster proved to be reproducible in vivo model to mimic parkinsonian phenotypes through exposure to the neurotoxin MPTP.

Biological interactions and attenuation of MPTP-induced toxicity in Drosophila melanogaster by Trans-astaxanthin.

Trans-astaxanthin (TA) is a carotenoid with amphipathic chemical structure found in yeast, and aquatic organisms. It is known to possess both antioxidative and anti-inflammatory properties. This study was carried out to investigate the ameliorative action of TA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in Drosophila melanogaster (Fruit fly). The flies were orally treated with TA (2.5 mg/10 g diet) and/or MPTP (500 µM) for 5 days. Thereafter, we evaluated selected biomarkers of locomotor deficits (acetylcholinesterase (AChE) and negative geotaxis), oxidative stress (hydrogen peroxide (H2O2), protein carbonyls (PC)), antioxidants (total thiols (T-SH), non-protein thiols, glutathione-S-transferase (GST) and catalase), and inflammation (nitric oxide (nitrite/nitrate) in the flies. Furthermore, we investigated molecular docking analysis of TA against Kelch-like ECH-associated protein 1 (Keap1)) of Homo sapiens and D. melanogaster. The results indicated that TA increased MPTP-induced decreased activities of AChE, GST, and catalase, as well as levels of non-protein thiols and T-SH compared with MPTP-treated flies (p < 0.05). Furthermore, TA attenuated inflammation, and improved locomotor deficit in the flies. The molecular docking data showed that TA had docking scores for binding both the Human and Drosophila Keap1, nearly closer to or higher than the standard inhibitor. The attenuating effects of TA against MPTP-induced toxicity could arise from its antioxidative and anti-inflammatory properties as well as its chemical structure.

Antioxidant activities of the leaves of Chrysophyllum albidum G.

Chrysophyllum albidum G. is a tropical plant and commonly found in Nigeria. It belongs to the sapotaceae family and used in folklore in the treatment of yellow fever, malaria, diarrhea, vaginal and dermatological infections. The study was aimed at investigating the antioxidant properties of this plant by employing the in vitro and in vivo experimental models. The effect of DPPH free radical scavenging activity on the fractions of petroleum ether, ethanol, butanol, ethylacetate, and water of C. albidum was determined. The ethyl acetate fraction was purified in column chromatography to obtain myricetin rhamnoside. Structure elucidation was done by NMR and mass spectroscopic techniques. Furthermore, ethanol extract was administered to five groups of eight rats per group. The animals in the normal group were administered with vehicle alone for 7 days. The positive control animals were given vehicle on the first four days, and with the vehicle and hepatotoxin (CCl(4)) on the fifth, sixth and seventh day. The animals in the treatment category were respectively administered with 500, 1000 and 1500 mg/kg b.w. of extract & distilled water for the first four days, and with distilled water, extract and CCl(4) on the last three days. Animals were subsequently anaesthetized and blood samples were collected for catalase (CAT), malondialdehyde (MDA), reduced gluthathione (GSH) and superoxide dismutase (SOD) assays. The petroleum ether fraction showed the least antiradical activity (4057.5 ± 809.6 g/kg) while ethyl ether exhibited the highest activity (414.4 ± 92.0 g/kg). Myricetin rhamnoside also exhibited an excellent radical scavenging activity (314.1 ± 60.2) which was comparable to the positive control. Result from animal study showed that C. albidum exhibited significant (p < 0.05) differences on the activity of CAT, MDA and GSH. The plant could therefore be employed as sources of natural antioxidant boosters and for the treatment of some oxidative stress disorders in which free radicals are implicated.

Benzo[a]pyrene and Benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide induced locomotor and reproductive senescence and altered biochemical parameters of oxidative damage in Canton-S Drosophila melanogaster.

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) commonly found in cigarette smoke, automobile exhaust fumes, grilled meat, and smoked food among others. Exposure to B[a]P is associated with a range of toxic effects including developmental, neurological, oxidative, inflammatory, mutagenic, carcinogenic and mortal. Efficient and more affordable experimental models like Drosophila melanogaster could provide more insight into the mechanism of PAH toxicity and help develop new strategies for prevention, diagnosis and treatment of PAH-related conditions. In this study, we examined the induction of some biochemical changes along with mortality and functional senescence by B[a]P and its metabolite, benzo[a]pyrene- 7,8-dihydrodiol-910-epoxide (BPDE) in the Canton-S strain of Drosophila melanogaster, with the aim to establish an alternative assay medium for B[a]P toxicity in flies. Flies were exposed to 2-200 µM of B[a]P and 1-10 µM of BPDE through diet for a seven-day survival assay followed by a four-day treatment to determine the effects of the compounds on negative geotaxis, fecundity and some biochemical parameters of oxidative damage. BPDE significantly reduced the survival rate of flies along the 7 days of exposure whereas B[a]P did not cause any significant change in the survival rate of flies. B[a]P and BPDE significantly reduced the climbing ability of flies after 4 days of exposure. Rate of emergence of flies significantly reduced at 10-200 µM of B[a]P and 5-10 µM of BPDE. Both compounds caused various levels of alterations in the values of reduced glutathione (GSH), total thiol (T-SH), glutathione-S-transferase (GST), catalase (CAT), hydrogen peroxide (H2O2), nitric oxide (NO) and acetylcholinesterase (AChE) of the flies. The compounds also exhibited high binding affinities and molecular interactions with the active site amino acid residues of Drosophila GST and the inhibitor binding site of Drosophila AChE in an in silico molecular docking analysis, with BPDE forming stable hydrogen bonds with AChE. Hence, the Canton-S strain of Drosophila melanogaster could offer a simple and affordable assay medium to study B[a]P toxicity.

D-Penicillamine prolongs survival and lessens copper-induced toxicity in Drosophila melanogaster.

D-penicillamine (DPA) is an amino-thiol that has been established as a copper chelating agent for the treatment of Wilson's disease. DPA reacts with metals to form complexes and/or chelates. Here, we investigated the survival rate extension capacity and modulatory role of DPA on Cu2+-induced toxicity in Drosophila melanogaster. Adult Wild type (Harwich strain) flies were exposed to Cu2+ (1 mM) and/or DPA (50 µM) in the diet for 7 days. Additionally, flies were exposed to acute Cu2+ (10 mM) for 24 h, followed by DPA (50 µM) treatment for 4 days. Thereafter, the antioxidant status [total thiol (T-SH) and glutathione (GSH) levels and glutathione S-transferase and catalase activities] as well as hydrogen peroxide (H2O2) level and acetylcholinesterase activity were evaluated. The results showed that DPA treatment prolongs the survival rate of D. melanogaster by protecting against Cu2+-induced lethality. Further, DPA restored Cu2+-induced depletion of T-SH level compared to the control (P < 0.05). DPA also protected against Cu2+ (1 mM)-induced inhibition of catalase activity. In addition, DPA ameliorated Cu2+-induced elevation of acetylcholinesterase activity in the flies. The study may therefore have health implications in neurodegenerative diseases involving oxidative stress such as Alzheimer's disease.

Neuroprotective role of 6-Gingerol-rich fraction of Zingiber officinale (Ginger) against acrylonitrile-induced neurotoxicity in male Wistar rats.

Background Acrylonitrile (AN) is a neurotoxin that is widely used to manufacture synthetic fibres, plastics and beverage containers. Recently, we reported the ameliorative role of 6-gingerol-rich fraction from Zingiber officinale (Ginger, GRF) on the chlorpyrifos-induced toxicity in rats. Here, we investigated the protective role of GRF on AN-induced brain damage in male rats. Methods Male rats were orally treated with corn oil (2 mL/kg, control), AN (50 mg/kg, Group B), GRF (200 mg/kg, Group C), AN [50 mg/kg+GRF (100 mg/kg) Group D], AN [(50 mg/kg)+GRF (200 mg/kg) Group E] and AN [(50 mg/kg)+N-acetylcysteine (AC, 50 mg/kg) Group F] for 14 days. Then, we assessed the selected markers of oxidative damage, antioxidant status and inflammation in the brain of rats. Results The results indicated that GRF restored the AN-induced elevations of brain malondialdehyde (MDA), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and Nitric Oxide (NO) levels. GRF also prevented the AN-induced depletion of brain glutathione (GSH) level and the activities of Glutathione S-transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in rats (p<0.05). Furthermore, GRF prevented the AN-induced cerebral cortex lesion and increased brain immunohistochemical expressions of Caspases-9 and -3. Conclusions Our data suggest that GRF may be a potential therapeutic agent in the treatment of AN-induced model of brain damage.

Hesperidin, a citrus bioflavonoid, alleviates trichloroethylene-induced oxidative stress in Drosophila melanogaster.

Trichloroethylene (TCE) is a chlorinated organic pollutant of groundwater with diverse toxic effects in animals and humans. Here, we investigated the ameliorative role of hesperidin, a citrus bioflavonoid on TCE-induced toxicity in Drosophila melanogaster. Four groups of D. melanogaster (50 flies/vial, with 5 vials/group) were exposed to ethanol (2.5%, control), HSP (400mg/10g diet), TCE (10µM/10g diet) and TCE (10µM/10g diet)+HSP (400mg/10g diet) respectively in the diet for 5days. Then, selected oxidative stress and antioxidant markers were evaluated. The results showed that TCE significantly increased the level of reactive oxygen species (ROS) and inhibited catalase, glutathione S-transferase and acetylcholinesterase (AChE) activities with concurrent depletion of total thiol level. However, co-administration of TCE and hesperidin mitigated TCE-induced depletion of antioxidants, and restored ROS level and AChE activity in the flies (p<0.05). Overall, hesperidin offered protective potency on TCE-induced oxidative stress in the flies via anti-oxidative mechanism.

Hepatic and renal toxicological evaluations of an industrial ovotoxic chemical, 4-vinylcyclohexene diepoxide, in both sexes of Wistar rats.

4-Vinylcyclohexene diepoxide (VCD) is an industrial occupational health hazard chemical because it induces ovotoxicity in rodents. The current study investigated the impacts of VCD on selected hepatic and renal markers of oxidative stress and inflammation in both sexes of Wistar rats. Thus, male and female rats were randomly distributed into four groups of ten rats per group, and dosed orally with VCD for 28days. The control male and female groups of rats received corn oil only, while each of the three remaining groups of both sexes of rats received VCD (100, 250 and 500mg/kg BW) respectively. Thereafter, biomarkers of hepatic and renal oxidative damage, inflammation and immunohistochemical expressions of iNOS, COX-2, caspase-9 and caspase-3 were evaluated. The results revealed that VCD increased markers of liver and kidney functions, oxidative damage and inflammation, and disrupted the antioxidant homeostasis of the rats (p<0.05). Lastly, VCD enhanced the immunohistochemical expressions of iNOS, COX-2, caspase-9 and caspase-3 in the liver of the rats. Thus, our data imply that VCD induced toxicity in the liver and kidney of rats via the combined impacts of oxidative damage and inflammation.

Effects of Tapinanthus globiferus and Zanthoxylum zanthoxyloides extracts on human leukocytes in vitro.

OBJECTIVE: This study aimed at investigating the genotoxicity and cytotoxicity effect of Tapinanthus globiferus and Zanthoxylum zanthoxyloides to human leukocytes. In addition, the reductive potential and the chemical composition of the two plant extracts were also determined. MATERIALS AND METHODS: Human leukocytes were obtained from healthy volunteer donors. The genotoxicity and cytotoxicity of T. globiferus and Z. zanthoxyloides were assessed using the comet assay and trypan blue exclusion, respectively. The antioxidant activity of the plant extracts was evaluated by the reducing power assay. Furthermore, high-performance liquid chromatography-diode array detector was used to characterize and quantify the constituents of these plants. RESULTS: T. globiferus (10-150 µg/mL) was neither genotoxic nor cytotoxic at the concentrations tested, suggesting that it can be consumed safely at relatively high concentrations. However, Z. zanthoxyloides showed cytoxicity and genotoxicity to human leukocytes at the highest concentration tested (150 µg/mL). In addition, the total reducing power of T. globiferus was found higher than Z. zanthoxyloides in potassium ferricyanide reduction. Both plants extract contained flavonoids (rutin and quercetin) and phenolic acids (chlorogenic and caffeic). CONCLUSION: The results obtained support the fact that some caution should be paid regarding the dosage and the frequency of use of Z. zanthoxyloides extract.