Biochemistry

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4-Vinylcyclohexene diepoxide disrupts sperm characteristics, endocrine balance and redox status in testes and epididymis of rats
(Informa UK Limited, 2017) Adedara, I. A.; Abolaji, A. O.; Ladipo, E. O.; Fatunmibi, O. J.; Abajingin, A. O.; Farombi, E. O.
Objectives: Exposure to 4-vinylcyclohexene diepoxide (VCD) was reported to induce testicular germ cell toxicity in rodents. However, there is paucity of information on the precise biochemical and molecular mechanisms of VCD-induced male reproductive toxicity. Methodology: This study investigated the influence of VCD on testicular and epidydimal functions following oral exposure of Wistar rats to VCD at 0, 100, 250 and 500 mg/kg for 28 consecutive days. Results: Administration of VCD significantly decreased the body weight gain and organosomatic indices of the testes and epididymis. When compared with the control, VCD significantly decreased superoxide dismutase and catalase activities in the testes whereas it significantly decreased superoxide dismutase activity but increased catalase activity in the epididymis. Moreover, while glutathione peroxidase activity and glutathione level remain unaffected, exposure of rats to VCD significantly increased glutathione S-transferase activity as well as hydrogen peroxide and malondialdehyde levels in testes and epididymis of the treated rats. The spermiogram of VCD-treated rats showed significant decrease in epididymal sperm count, sperm progressive motility, testicular sperm number and daily sperm production when compared with the control. Administration of VCD significantly decreased circulatory concentrations of follicle-stimulating hormone, luteinizing hormone and testosterone along with testicular and epididymal degeneration in the treated rats. Immunohistochemical analysis showed significantly increased cyclooxygenase-2, inducible nitric oxide synthase, caspase-9 and caspase-3 protein expressions in the testes of VCDtreated rats. Conclusion: Exposure to VCD induces testicular and epidydimal dysfunctions via endocrine suppression, disruption of antioxidant enzymes activities, increase in biomarkers of oxidative stress, inflammation and apoptosis in rats.
6-Gingerol abates benzo[a]pyrene-induced colonic injury via suppression of oxido-inflammatory stress responses in BALB/c mice
(Elsevier B.V., 2019) Ajayi, B. O. || ||; Adedara, I. A.; Farombi, E. O.
Exposure to benzo[a]pyrene (BaP), the most toxic polycyclic aromatic hydrocarbon and a procarcinogen, is a global health concern which necessitates preventive measures. [6]-Gingerol (6-G), the most pharmacologically active constituent of ginger has been reported to promote gut health in various experimental settings. This study investigated the role of 6-G in BaP-induced colonic oxidative and inflammatory stress responses in mice. Experimental mice were randomly assigned into five groups of eight mice each and were orally gavage with BaP (125 mg/kg) singly or in combination with 6-G at 50 and 100 mg/kg for 14 consecutive days. Following sacrifice, the colonic activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), myeloperoxidase (MPO) as well as levels of glutathione (GSH), nitrites and lipid peroxidation (LPO) were assessed spectrophotometrically. Moreover, colonic concentration of epoxide hydrolase (EPXH), tumor necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were assessed using ELISA. Administration of 6-G augmented BaP detoxification and colonic antioxidant status by increasing the EPXH, GST, SOD and CAT activities, GSH level with concomitant decrease in MDA level when compared with BaP alone group. In addition, 6-G suppressed BaP-induced colonic inflammation by decreasing MPO activity as well as nitrites, TNF-α, IL-1β, COX-2 and iNOS levels when compared with BaP alone group. In conclusion, 6-G protected against a decrease in colonic epoxide detoxifying enzymes and antioxidant defense mechanisms caused by BaP.
6-Gingerol delays tumorigenesis in benzo[a]pyrene and dextran sulphate sodium-induced colorectal cancer in mice
(Elsevier Ltd., 2020) Farombi, E. O. || ||; Ajayi, B. O.; Adedara, I. A.
Colorectal cancer (CRC) has been linked to dietary consumption of benzo[a]pyrene (B[a]P). 6-Gingerol (6-G), a component of ginger has been reported to possess anti-inflammatory and antioxidant activities, but little is known regarding the mechanism of 6-G in CRC chemoprevention. We therefore investigated the effect of 6-G on B[a]P. and dextran sulphate sodium (DSS) induced CRC in mice. Mice in Group I and Group II received corn oil and 6-G orally at 2 ml/kg and 100 mg/kg, respectively for 126 days. Group III were administered 125 mg/kg of B [a]P for 5 days followed by 3 cycles of 4% dextran sulphate sodium (DSS). Group IV received 6-G for 7 days followed by co-administration with 125 mg/kg of B[a]P. for 5 days and 3 cycles of 4% DSS. Tumor formation was reduced and expression of Ki-67, WNT3a, DVL-2 and p-catenin following 6-G exposure. Also, 6-G increases expression of APC, P53, TUNEL positive nuclei and subsequently decreased the expression of TNF-a, IL-1p, INOS, COX-2 and cyclin D1. 6-G inhibited angiogenesis by decreasing the concentration of VEGF, Angiopoietin- 1, FGF and GDF-15 in the colon of B[a]P. and DSS exposed mice. Overall, 6-G attenuated B[a]P and DSS-induced CRC in mice via anti-inflammatory, anti-proliferative and apoptotic mechanisms.
6-Gingerol improves testicular function in mice model of chronic ulcerative colitis
(Sage Publishers, 2018) Farombi, E. O.; Adedara, I. A.; Ajayi, B. O.; Idowu, T. E.; Eriomala, O. O.; Akinbote, F. O.
The persistent inflammation and oxidative stress at the local site in ulcerative colitis reportedly extend to the testes via systemic circulation resulting in testicular dysfunction. The influence of 6-gingerol (6G), a phenolic compound isolated from Zingiber officinale, on colitis-mediated testicular dysfunction in mice was investigated in this study. Chronic ulcerative colitis was induced in mice using 2.5% dextran sulfate sodium (DSS) in drinking water for three cycles. Each cycle consisted of 7 consecutive days of exposure to DSS-treated water followed by 14 consecutive days of normal drinking water. 6G (100 mg/kg) or sulfasalazine (SZ; 100 mg/kg) was orally administered alone or in combination with DSS-treated water during the three cycles. SZ served as standard reference drug for colitis in this study. 6G significantly prevented the incidence of rectal bleeding, decrease in the body weight gain and colon mass index in DSS-exposed mice. 6G significantly prevented colitis-mediated decreases in luteinizing hormone, follicle-stimulating hormone and testosterone and decreases oxidative stress indices, pro-inflammatory cytokines and caspase-3 activity with concomitant augmentation of antioxidant enzymes activities, sperm characteristics, marker enzymes of testicular function and histoarchitecture in DSS-exposed mice. 6G exerted protective influence against ulcerative colitis-induced testicular damage via mechanisms involving its antioxidant and anti-inflammatory properties.
6-Gingerol-Rich fraction from Zingiber officinale prevents hematotoxicity and oxidative damage in kidney and liver of rats exposed to Carbendazim
(Taylor & Francis Group, LLC, 2016) Salihu, M.; Ajayi, B. O.; Adedara, I. A.; Farombi, E. O.
Ginger (Zingiber officinale) is a globally marketed flavoring agent and cooking spice with a long history of human health benefits. The fungicide carbendazim (CBZ) is often detected in fruits and vegetables for human nutrition and has been reported to elicit toxic effects in different experimental animal models. The present study investigated the protective effects of 6-Gingerol-rich fraction (6-GRF) from ginger on hematotoxicity and hepatorenal damage in rats exposed to CBZ. CBZ was administered at a dose of 50 mg/kg alone or simultaneously administered with 6-GRF at 50, 100, and 200 mg/kg, whereas control rats received corn oil alone at 2 mL/kg for 14 days. Hematological examination showed that CBZ-mediated toxicity to the total white blood cell (WBC), neutrophils, lymphocytes, and platelets counts were normalized to the control values in rats co-treated with 6-GRF. Moreover, administration of CBZ significantly decreased the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase as well as glutathione level in the livers and kidneys of rats compared with control. However, the levels of hydrogen peroxide (H2O2) and malondialdehyde were markedly elevated in kidneys and livers of CBZ-treated rats compared with control. The significant elevation in the plasma indices of renal and hepatic dysfunction in CBZ-treated rats was confirmed by light microscopy. Coadministration of 6-GRF exhibited chemoprotection against CBZ-mediated hematotoxicity, augmented antioxidant status, and prevented oxidative damage in the kidney and liver of rats.
6-Gingerol-rich fraction prevents disruption of histomorphometry and marker enzymes of testicular function in carbendazim-treated rats
(Blackwell Verlag GmbH, 2017) Salihu, M.; Ajayi, B. O.; Adedara, I. A.; Farombi, E. O.
Previous investigations demonstrated that 6-gingerol-rich fraction (6-GRF) prevented testicular toxicity via inhibition of oxidative stress and endocrine disruption in CBZ-treated rats. The influence of 6-GRF on alterations in histomorphometry and marker enzymes of testicular function in CBZ-treated rats which hitherto has not been reported was investigated in this study. The animals were orally administered either CBZ (50 mg/kg) alone or in combination with 6-GRF (50, 100 and 200 mg/kg) for 14 consecutive days. Histomorphormetric analysis demonstrated that 6-GRF significantly prevented CBZ-mediated increase in the organo-somatic index of the testes and seminiferous tubular diameter as well as the reduction in epithelium height and tubular length of testes in the rats. Similarly, 6-GRF ameliorated CBZ-induced disruption in the epithelium height as well as in the proportion of tubule and interstitium of the epididymis the treated rats. Furthermore, 6-GRF prevented CBZ-mediated increase in testicular acid phosphatase activity and the decrease in testicular alkaline phosphatase, aminotransferases, glucose-6- phosphate dehydrogenase and lactate dehydrogenase activities. Moreover, 6-GRF ameliorated CBZ-induced reduction in the testicular and epididymal sperm count and sperm motility in the treated rats. Conclusively, 6-GRF enhances key functional enzymes involve in spermatogenesis and maintains histo-architecture of testes and epididymis in CBZ-treated rats.
Abatement of the dysfunctional hypothalamic–pituitary–gonadal axis due to ciprofloxacin administration by selenium in male rats
(Wiley Periodicals LLC, 2021) Adedara, I. A.; Awogbindin, I. O.; Mohammed, K. A.; Da-Silva, O. F.; Farombi, E. O.
The present study examined the influence of selenium on ciprofloxacin‐mediated reproductive dysfunction in rats. The research design consisted of five groups of eight animals each. The rats were administered 135 mg/kg body weight of ciprofloxacin per se or simultaneously with selenium at 0.25 and 0.5 mg/kg for 15 uninterrupted days. Antioxidant and inflammatory indices were assayed using the testes, epididymis, and hypothalamus of the animals after sacrifice. Results revealed that ciprofloxacin treatment per se interfered with the reproductive axis as demonstrated by diminished serum hormonal levels, sperm quality, and enzymatic indices of testicular function, which were, however, abrogated following selenium co‐treatment. Besides this, administration of selenium attenuated the depletion of glutathione level, inhibition of catalase, superoxide dismutase, glutathione‐Stransferase and glutathione peroxidase activities with a concomitant reduction in reactive oxygen and nitrogen species, and lipid peroxidation in ciprofloxacintreated in rats. Selenium treatment also mitigated ciprofloxacin‐mediated elevation in nitric oxide level and of myeloperoxidase activity as well as histological lesions in the animals. Overall, selenium attenuated impairment in the male reproductive axis due to ciprofloxacin treatment through abatement of inflammation and oxidative stress in rats.
Acute diethyl nitrosamine and cadmium co‐exposure exacerbates deficits in endocrine balance, sperm characteristics and antioxidant defence mechanisms in testes of pubertal rats
(Blackwell Verlag GmbH, 2019) Owumi, S. E.; Adedara, I. A.; Duro-Ladipo, A.; Farombi, E. O.
Diethylnitrosamine (DEN) and cadmium are environmental contaminants of known poisonous consequences in animals and humans. We examined the influence of acute oral co‐exposure to DEN (10 mg/kg) and cadmium (5 mg/kg) on endocrine balance, semen and antioxidant status in rat testes. The results indicated decreases (p < 0.05) in the weight of the testis and organo‐somatic index of the testes in rats administered with either DEN or cadmium were aggravated in the co‐exposed rats. Serum concentrations of follicle‐stimulating hormone (FSH), luteinising hormone (LH) and testosterone decreased, and were more pronounced in rats co‐treated with DEN and cadmium. Enzymatic and non-enzymatic antioxidant activities decreased following separate exposure to DEN and cadmium, and were increased in rats co‐treated with DEN and cadmium. The significant (p < 0.05) increases in malondialdehyde (MDA) was complemented by marked increase in sperm abnormalities, reduction in the sperm count, motility and viability compared with control. Histologically, co‐exposure to DEN and cadmium aggravates their discrete effects on the testes. Co‐exposure to DEN and cadmium elicited more severe endocrine disruption and testicular oxidative damage in rats, revealing additive adverse effects on testicular functions in rats and as such, may put exposed individual at greater risk.
Aflatoxin B1 disrupts the androgen biosynthetic pathway in rat Leydig cells
(Elsevier Ltd., 2014) Adedara, I. A.; Nanjappa, M. K.; Farombi, E. O.; Akingbemi, B. T.
The present study investigated if Aflatoxin B1 (AFB1), a potent and naturally occurring mycotoxin, interferes with the steroidogenic pathway in rat Leydig cells. Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone (T) that maintains the male phenotype and support fertility. Leydig cells, isolated from 35-day-old male Long-Evans rats (Rattus norvegicus), were incubated with AFB1 at 0, 0.01, 0.1, 1, 10 lM followed by measurement of T secretion by radioimmunoassay and analysis of protein expression in western blots. Results demonstrated that AFB1 suppressed testosterone secretion in a dose-dependent manner and inhibited expression of cholesterol transporter steroidogenic acute regulatory protein (StAR) and steroidogenic enzymes [(3b-hydroxysteroid dehydrogenase (3b-HSD) and 17b-hydroxysteroid dehydrogenase enzyme (HSD17B3)]. Protein expression analysis showed that AFB1 treatment increased ERK phosphorylation but suppressed p38 MAPK and JNK activation in Leydig cells. AFB1-induced inhibition of Leydig cells was alleviated by co-treatment with the ERK inhibitor UO 126, implying that ERK mediates, at least in part, the inhibitory effects of AFB1 in Leydig cells. The findings highlight potential extra-hepatic effects of aflatoxin exposure and indicate that exposure to AFB1 has significant reproductive health implications for consumers of contaminated products even under conditions of low dietary toxin levels.
ANTIMALARIAL AND ANTITUBERCULAR ACTIVITIES OF CRUDE METHANOL EXTRACT AND FRACTIONS OF THE BULB OF CRINUM JAGUS ( Linn.)
(2015-02) KOLAWOLE, ADEBOLA OLAYEMI
Crinum jagus is a medicinal plant used traditionally to treat tuberculosis, malaria and other bacterial infections. However, there are limited documented scientific studies to substantiate the use of this plant. Due to increase in resistance to malaria and tuberculosis drugs, the need for the development of other drugs is pertinent. This study was designed to determine the pharmacological activities of extract and fractions of Crinum jagus. Methanol extract of C. jagus obtained by soxhlet extraction was subjected to phytochemical analysis and fractionated using column chromatography. Antitubercular and antimicrobial activities of the extract and its fractions were evaluated against isolates of Mycobacterium tuberculosis and selected microorganisms using the disc and agar diffusion methods. Antimalarial activity was assessed in vivo using Rane’s test in Plasmodium berghei infected mice (n = 80 in 10 groups) treated orally with tween 80 (control), 10, 25, 50 and 75 mg/kg of extract and its fractions at 10 mg/kg respectively, while chloroquine (10 mg/kg) and arteether (3 mg/kg) groups served as positive controls. Anti-inflammatory potential was assessed in rats using carrageenan-induced paw inflammatory model. In vitro antioxidant potentials were determined spectrophotometrically using 1,1-diphenyl-2-picryl hydrazyl (DPPH), hydroxyl radical scavenging activities, Total Flavonoids Contents (TFC) and Phenolic Contents (TPC) Antioxidant indices- Superoxide dismutase (SOD) and Catalase (CAT) activities and levels of Malondialdehyde (MDA) and reduced Glutathione (GSH) were determined by spectrophotometry. Aspartate (AST) and Alanine (ALT) amino transferases and Alkaline Phosphatase (ALP) were estimated spectrophotometrically. Data were analysed by Student’s t test at p = 0.05. Phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols and steroids in the crude extract. The extract and its fractions (F1, F2 and F3) showed a concentration- dependent inhibition of Mycobacterium tuberculosis, with F1 having the lowest IC50of : 0.22mg/mL relative to rifampicin (IC50 : 0.19mg/mL) and isoniazid (0.23mg/mL). The extract at 10, 25, 50, 75 mg/kg and F1, F2 and F3 at 10 mg/kg suppressed parasitaemia in Plasmodium berghei infected mice by 70.0, 76.0, 79.0, 87.0% and 89.0, 76.0, 78.0% respectively relative to chloroquine (100%) and arteether (89.0%). The extract at 10, 25, 50, 75 mg/kg and F1, F2 and F3 at 10 mg/kg inhibited oedema in rat paws by 26.0, 30.0, 32.0, 66.0% and 80.0, 25.0, 52.0% UNIVERSITY OF IBADAN LIBRARY iii respectively when compared with indomethacin (95.0%). The extract and its fractions significantly scavenged DPPH and hydroxyl radical in vitro. The TPC and TFC of extract, F1, F2 and F3 at 500 μg/ml were 0.310, 0.460, 0.240, 0.380 μg/mg and 0.523, 0.864, 0.396, 0.643 μg/g respectively. The extract and its fractions significantly reduced MDA level while GSH, SOD and CAT levels were increased. Activities of AST, ALT and ALP were significantly increased at 50 and 75 mg/kg body weight of extract . Crinum jagus exhibited antitubercular, antimalarial and anti-inflammatory activities via scavenging of radicals and antioxidative mechanism. This indicates a promising potential of the plant for drug development. Keywords: Crinum jagus, antituberculosis, antimalarial, antioxidant. Word Count: 471 .
Benzo(a)pyrene induces oxidative stress, pro-inflammatory cytokines, expression of nuclear factor-kappa B and deregulation of wnt/beta- catenin signaling in colons of BALB/c mice201
(Elsevier Ltd., 2016) Ajayi, B. O.; Adedara, I. A.; Farombi, E. O.
The incidence of colonic toxicity has been epidemiologically linked to the consumption of foods contaminated with benzo[a]pyrene (B[a]P). The present study investigated the effects of B[a]P on biomarkers of colonic stress, inflammation and Wnt/β-catenin signaling in colon of BALB/c mice. B[a]P was administered orally at 62.5, 125 and 250 mg/kg of B[a]P for 7 days by oral gavage. Exposure to B[a]P significantly decreased the colonic antioxidant enzyme activities and glutathione levels with concomitant significant increase in myeloperoxidase activity, nitric oxide and lipid peroxidation levels. Colon histopathology results showed treatment-related lesions characterized by atrophy, mucosal ulceration and gland erosion in the B[a]P-treated mice. Immunohistochemistry analysis showed that B[a]P treatment increased the protein expression of nuclear factor kappa B, pro-inflammatory cytokines namely tumor necrosis factor alpha and interleukin-1β, as well as cyclooxygenase-2 and inducible nitric oxide synthase in the mice colon. Altered canonical Wnt signaling was confirmed using diaminobenzidine staining for p38 mitogen activated protein kinase, β-catenin expression and absence of adenomatous polyposis coli following B[a]P administration. The present data highlight that exposure to B[a]P induces colonic injury via induction of oxidative and nitrosative stress, inflammatory biomarkers and dysregulation of Wnt/β-catenin signaling, thus confirming the role of B[a]P in the pathogenesis of colonic toxicity.
Biochemical and behavioral deficits in the lobster cockroach Nauphoeta cinerea model of methylmercury exposure
(The Royal Society of Chemistry, 2015) Adedara, I. A.; Rosemberg, D. B..; Souza, D. O.; Kamdem, J. P.; Farombi, E. O.; Aschnerd, M.; Rocha, J. B. T.
Methylmercury (MeHg) is well-known for its neurodevelopmental effects both in animals and in humans. As an alternative to utilizing conventional animal models, this study evaluated behavioral and biochemical parameters using the nymphs of the lobster cockroach Nauphoeta cinerea. Animals were exposed to MeHg at 0, 0.03125, 0.0625, 0.125, 0.25 and 0.5 mg per g feed for 35 consecutive days. Locomotor activity and exploratory profiles were analyzed using video-tracking software during a 10 minute trial. Subsequently, biochemical estimations were carried out using cockroach heads. MeHg exposure caused behavioral impairment as evidenced by a significant decrease in distance travelled, time spent walking, turn angle and body rotation. The marked decrease in the exploratory profiles of MeHg-exposed cockroaches was confirmed by track plots, whereas occupancy plot analyses revealed a gradual dispersal in homebase formation, starting from 0.0625 mg per g feed. Biochemically, MeHg exposure significantly decreased acetylcholinesterase activity (AChE), an enzyme which plays a pivotal role in neurotransmission. Moreover, MeHg caused increased oxidative stress as evidenced by decreased total thiol levels and glutathione S-transferase (GST) activity, along with increased 2’,7’-dichlorofluorescein (DFCH) oxidation and thiobarbituric acid reactive substance (TBARS) production. In conclusion, these data demonstrated that Nauphoeta cinerea mimics the behavioral and biochemical deficits observed in rodents exposed to MeHg, thus highlighting its validity as an alternative model for basic toxicological studies.
Chemoprotection of ethylene glycol monoethyl ether-induced reproductive toxicity in male rats by kolaviron, isolated biflavonoid from Garcinia kola seed
(Sage Publishers, 2012) Adedara, I. A.; Farombi, E. O.
"The present study investigated the protective effect of kolaviron, a biflavonoid from the seed of Garcinia kola, on ethylene glycol monoethyl ether (EGEE)–induced reproductive toxicity in male rats. The protective effect of kolaviron was validated using vitamin E, a standard antioxidant. EGEE was administered at a dose of 200 mg/kg. Other groups of rats were simultaneously treated with kolaviron (100 and 200 mg/kg) and vitamin E (50 mg/kg) for 14 days. EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities but markedly increased the glutathione-Stransferase (GST) and lactate dehydrogenase (LDH) activities in the testes. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GPx, GST and LDH as well as in the level of GSH but significantly increased SOD activity with concomitant increase in hydrogen peroxide and malondialdehyde levels in both testes and spermatozoa. EGEE-exposed rats showed marked testicular degeneration with concomitant decrease in spermatozoa quantity and quality. Overall, EGEE causes reproductive dysfunction in rats by altering antioxidant systems in the testes and spermatozoa. Kolaviron or vitamin E exhibited protective effects against EGEE-induced male reproductive toxicity by enhancement of antioxidant status and improvement in spermatozoa quantity and quality.
Chemoprotective effects of kolaviron on ethylene glycol monoethyl ether-induced pituitary-thyroid axis toxicity in male rats
(Blackwell Verlag GmbH, 2012) Adedara, I. A.; Farombi, E. O.
Endocrine disrupting chemicals cause reproductive dysfunction by interacting with intricate regulation and cellular processes involve in spermatogenesis. This study investigated the probable mechanism of action of ethylene glycol monoethyl ether (EGEE) as an antiandrogenic compound as well as the effects of kolaviron upon co-administration with EGEE in rats. Adult male rats were exposed to EGEE (200 mg kg_1 bw) separately or in combination with either kolaviron [100 (KV1) and 200 (KV2) mg kg_1 bw] or vitamin E (50 mg kg_1bw) for 14 days. Western blot analysis revealed that the administration of EGEE adversely affected steroidogenesis in experimental rats by decreasing the expression of steroid acute regulatory (StAR) protein and androgen-binding protein (ABP). EGEE significantly decreased the activities of 3b-hydroxysteroid dehydrogenase (3b-HSD) and 17b-hydroxysteroid dehydrogenase (17b-HSD) but markedly increased sialic acid concentration in rat testes. EGEE-treated rats showed significant decreases in plasma levels of luteinising hormone (31%), testosterone (57.1%), prolactin (80.9%), triiodothyronine (65.3%) and thyroxine (41.4%), whereas follicle-stimulating hormone was significantly elevated by 76.9% compared to the control. However, co-administration of kolaviron or vitamin E significantly reversed the EGEE-induced steroidogenic dysfunction in rats. This study suggests that kolaviron may prove promising as a chemoprotective agent against endocrine pathology resulting from EGEE exposure.
Chemoprotective role of quercetin in manganese-induced toxicity along the brain-pituitary-testicular axis in rats
(Elsevier Ireland Ltd., 2017) Adedara, I. A.; Subair, T. I.; Ego, V. C.; Oyediran, O.; Farombi, E. O.
Reproductive dysfunction in response to manganese exposure has been reported in humans and animals. Quercetin, a bioflavonoid widely distributed in fruits, vegetables and beverages has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic activities in different experimental model systems. However, there is dearth of scientific information on the influence of quercetin on manganese-induced reproductive toxicity. This study was designed to evaluate the influence of quercetin on manganese-induced functional alterations along the brain–pituitary–testicular axis in rats. Manganese was administered alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Results indicated that quercetin significantly (p < 0.05) inhibited manganese-induced elevation in biomarkers of oxidative stress whereas it increased antioxidant enzymes activities and glutathione level in the brain, testes and epididymis of the treated rats. Furthermore, quercetin mediated suppression of inflammatory indices and caspase-3 activity was accompanied by preservation of histo-architectures of the brain, testes and epididymis in manganese-treated rats. The significant reversal of manganese-induced decreases in reproductive hormones (i.e. luteinizing hormone, follicle-stimulating hormone and testosterone) and testicular activities of acid phosphatase, alkaline phosphatase and lactate dehydrogenase by quercetin was complemented by an increase in sperm quality and quantity in the treated rats. Collectively, quercetin modulated manganese-induced toxicity along the brain–pituitary–testicular axis in rats via its intrinsic antioxidant, anti-inflammatory and anti-apoptotic activities, and may thus represent a potential pharmacological agent against manganese-induced male reproductive deficits in humans.
Chronic ciprofloxacin and atrazine co-exposure aggravates locomotor and exploratory deficits in non-target detritivore speckled cockroach (Nauphoeta cinerea)
(Springer-Verlag GmbH, 2021) Adedara, I. A. || || || || || || ||; Godswill, U. S.; Mike. M. A.; Afolabi, B. A.; Amorha, C. C.; Sule, J.; Rocha, J. B. T.; Farombi, E. O.
The global detection of ciprofloxacin and atrazine in soil is linked to intensive anthropogenic activities in agriculture and inadvertent discharge of industrial wastes to the environment. Nauphoeta cinerea is a terrestrial insect with cosmopolitan distribution and great environmental function. The current study probed the neurobehavioral and cellular responses of N. cinerea singly and jointly exposed to atrazine (1.0 and 0.5 μg g−1 feed) and ciprofloxacin (0.5 and 0.25 μg g−1 feed) for 63 days. Results demonstrated that the reductions in the body rotation, maximum speed, turn angle, path efficiency, distance traveled, episodes, and time of mobility induced by atrazine or ciprofloxacin per se was exacerbated in the co-exposure group. The altered exploratory and locomotor in insects singly and jointly exposed to ciprofloxacin and atrazine were verified by track plots and heat maps. Furthermore, we observed a decrease in acetylcholinesterase and anti-oxidative enzyme activities with concomitant elevation in the levels of lipid peroxidation, nitric oxide, and reactive oxygen and nitrogen species were significantly intensified in the midgut, hemolymph, and head of insects co-exposed to ciprofloxacin and atrazine. In conclusion, exposure to binary mixtures of ciprofloxacin and atrazine elicited greater locomotor and exploratory deficits than upon exposure to the individual compound by inhibiting acetylcholinesterase activity and induction of oxido-inflammatory stress responses in the insects. N. cinerea may be a usable model insect for checking contaminants of ecological risks.
Curcumin and Kolaviron Ameliorate Di-n-Butylphthalate-Induced Testicular Damage in Rats
(Nordic Pharmacological Society, 2007) Farombi, E. O.; Abarikwu, S. O.; Adedara, I. A.; Oyeyemi, M. O.
The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days significantly decreased the relative testicular weights compared to the controls, while the weights of other organs remained unaffected. Curcumin or kolaviron did not affect all the organ weights of the animals. While only DBP treatment significantly increased the testicular malondialdehyde level and gamma-glutamyl transferase activity (γ-GT), it markedly decreased glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, sperm γ -GT activities and serum testosterone level compared to the control group. Data on cauda epididymal sperm count and live/dead ratio were not significantly affected in the DBPtreated rats. Alone, DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa in comparison to control. DBP-treated rats showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP-induced injuries in biochemical, spermatological parameters and histological structure of testis were recovered by treatment with kolaviron or curcumin. The pattern in the behaviour of these compounds might be correlated with their structural variations. Our results indicate that kolaviron and curcumin protect against testicular oxidative damage induced by DBP. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.
CYTOTOXICITY OF HEXAVALENT CHROMATE COMPOUNDS IN CH310T1/2 CELLS AND CYTOMODULATION BY SODIUM ARSENITE AND METHANOL EXTRACT OF Rauvolfia vomitora (Afzel) IN MICE.
(2015-02) AKINWUMI, K. A.
Exposure to certain hexavalent chromate compounds (HCC) causes lung and colon cancers. Their mechanisms of cytotoxicity are unclear, but believed to be affected by ascorbate and particle size. However, their role is not clearly defined. Co-exposure with sodium arsenite (SA) is common, but its effect on HCC toxicity is unknown. Current therapy has side effects, necessitating the search for antidote from unexplored natural products such as Rauvolfia vomitora (RV). This study therefore investigates the effect of particle size and ascorbate on cytotoxity of selected HCC [lead chromate (PbCrO4), barium chromate (BaCrO4), strontium chromate (SrCrO4) and potassium dichromate (K2Cr2O7)] in C3H10T1/2 cells and cytomodulatory effects of SA and RV in mice. The effect of ascorbate, dehydroascorbate and particle size on HCC cytotoxicity in C3H10T1/2 cells was determined by measuring survival fraction and yield of foci by microscopy. Actin and cellular ultrastructure disruption and induction of cell death were assessed by electron and fluorescent microscopy. The molecular mechanisms of cytotoxicity and transformation were evaluated in eighty-four cell death genes using real time (RT2) gene array, while cell cycle analysis was done by flow cytometry. Leaves of RV were air dried, powdered and extracted with methanol. Forty male mice (20-25g) were divided into 8 groups of 5 Swiss albino mice each and treated with water (control), RV (275 mg/Kg), SA (2.5 mg/kg), K2Cr2O7 (12 mg/Kg), SA + K2Cr2O7, RV + SA, RV + K2Cr2O7, RV + SA + K2Cr2O7. Rauvolfia vomitora was given orally for seven days, while K2Cr2O7 and SA were administered on day seven. Serum aspartate and alanine aminotransferases (AST and ALT), catalase, glutathione-S-transferase (GST), glutathione and malondialdehyde (MDA) levels were determined by spectrophotometry. Micronucleated polychromatic erythrocytes (mPCEs) were evaluated by microscopy. Data were analysed using ANOVA and Student’s t- test at p= 0.05. Survival fraction of control cells was 1.0, treatment with PbCrO4 and ≤ 12.5 µM ascorbate or ≤ 2 µM dehydroascorbate decreased it to 0.4. The 15-20 µM ascorbate and 3-4 µM dehydroascorbate reversed it to 0.7. Exposure of cells to small (≤ 3 µm) and large particles (≤ 8 µm) of PbCrO4, BaCrO4 and SrCrO4 resulted in a dose-dependent decrease in survival. The total foci were higher for PbCrO4 (3.8) with large particles and BaCrO4 (6.6) with small particles. Phagocytosis of particles was time-dependent. The HCC treatment led to G2/M and S phase arrest, anucleation, actin disruption and mixed cell death. Thirty-four cell death genes including Bax and Casp3 were up-regulated by 4 folds and six including Bcl-2 and Traf2 were down- regulated in treated cells. Twenty-one anti-apoptotic and autophagy genes including Atg5 and Bcl-2 were up-regulated in PbCrO4 transformed cells. The K2Cr2O7 and/ or SA significantly increased mPCEs, AST, ALT, catalase and MDA levels while glutathione and GST were reduced. The RV restored the markers towards normal values. Cytotoxicty of chromate compounds is particle size and ascorbate dependent. The cytotoxicity might be due to actin disruption, micronuclei induction and cell cycle arrest. Methanol extract of Rauvolfia vomitora modulated the toxicity in mice.
CYTOTOXICITY OF HEXAVALENT CHROMATE COMPOUNDS IN CH310T1/2 CELLS AND CYTOMODULATION BY SODIUM ARSENITE AND METHANOL EXTRACT OF Rauvolfia vomitora (Afzel) IN MICE.
(2015-02) AKINWUMI, KAZEEM AKINYINKA
Exposure to certain hexavalent chromate compounds (HCC) causes lung and colon cancers. Their mechanisms of cytotoxicity are unclear, but believed to be affected by ascorbate and particle size. However, their role is not clearly defined. Co-exposure with sodium arsenite (SA) is common, but its effect on HCC toxicity is unknown. Current therapy has side effects, necessitating the search for antidote from unexplored natural products such as Rauvolfia vomitora (RV). This study therefore investigates the effect of particle size and ascorbate on cytotoxity of selected HCC [lead chromate (PbCrO4), barium chromate (BaCrO4), strontium chromate (SrCrO4) and potassium dichromate (K2Cr2O7)] in C3H10T1/2 cells and cytomodulatory effects of SA and RV in mice. The effect of ascorbate, dehydroascorbate and particle size on HCC cytotoxicity in C3H10T1/2 cells was determined by measuring survival fraction and yield of foci by microscopy. Actin and cellular ultrastructure disruption and induction of cell death were assessed by electron and fluorescent microscopy. The molecular mechanisms of cytotoxicity and transformation were evaluated in eighty-four cell death genes using real time (RT2) gene array, while cell cycle analysis was done by flow cytometry. Leaves of RV were air dried, powdered and extracted with methanol. Forty male mice (20-25g) were divided into 8 groups of 5 Swiss albino mice each and treated with water (control), RV (275 mg/Kg), SA (2.5 mg/kg), K2Cr2O7 (12 mg/Kg), SA + K2Cr2O7, RV + SA, RV + K2Cr2O7, RV + SA + K2Cr2O7. Rauvolfia vomitora was given orally for seven days, while K2Cr2O7 and SA were administered on day seven. Serum aspartate and alanine aminotransferases (AST and ALT), catalase, glutathione-S-transferase (GST), glutathione and malondialdehyde (MDA) levels were determined by spectrophotometry. Micronucleated polychromatic erythrocytes (mPCEs) were evaluated by microscopy. Data were analysed using ANOVA and Student‟s t- test at p= 0.05. Survival fraction of control cells was 1.0, treatment with PbCrO4 and ≤ 12.5 μM ascorbate or ≤ 2 μM dehydroascorbate decreased it to 0.4. The 15-20 μM ascorbate and 3-4 μM dehydroascorbate reversed it to 0.7. Exposure of cells to small (≤ 3 μm) and large particles (≤ 8 μm) of PbCrO4, BaCrO4 and SrCrO4 resulted in a dose-dependent decrease in survival. The total foci were higher for PbCrO4 (3.8) with large particles and BaCrO4 (6.6) with small particles. Phagocytosis of particles was time-dependent. The HCC treatment led to G2/M and S phase arrest, anucleation, actin disruption and mixed cell death. Thirty-four cell death genes including Bax and Casp3 were up-regulated by 4 folds and six including Bcl-2 and Traf2 were down- regulated in treated cells. Twenty-one anti-apoptotic and autophagy genes including Atg5 and Bcl-2 were up-regulated in PbCrO4 transformed cells. The K2Cr2O7 and/ or SA significantly increased mPCEs, AST, ALT, catalase and MDA levels while glutathione and GST were reduced. The RV restored the markers towards normal values. Cytotoxicty of chromate compounds is particle size and ascorbate dependent. The cytotoxicity might be due to actin disruption, micronuclei induction and cell cycle arrest. Methanol extract of Rauvolfia vomitora modulated the toxicity in mice. Keywords: Hexavalent chromate compounds, Sodium arsenite, Rauvolfia vomitora, Cytotoxicity Word counts: 494
Dietary co-exposure to methylmercury and monosodium glutamate disrupts cellular and behavioral responses in the lobster cockroach, Nauphoeta cinerea model
(Elsevier B.V., 2018) Afolabi, B. A. || || ||; Adedara, I. A.; Souza, D. O.; Rocha, J. B. T.
The present study aims to investigate the effect of monosodium glutamate (MSG) both separately and combined with a low dose of methylmercury (MeHg) on behavioral and biochemical parameters in Nauphoeta cinerea (lobster cockroach). Cockroaches were fed with the basal diet alone, basal diet + 2% NaCl, basal diet + 2% MSG; basal diet+0.125 mg/g MeHg, basal diet+0.125 mg/g MeHg + 2% NaCl; and basal diet+0.125 mg/g MeHg + 2% MSG for 21 days. Behavioral parameters such as distance traveled, immobility and turn angle were automatically measured using ANY-maze video tracking software (Stoelting, CO, USA). Biochemical end-points such as acetylcholinesterase (AChE), glutathione-S-transferase (GST), total thiol and TBARS were also evaluated. Results show that MeHg+NaCl, increased distance traveled while MeHg+MSG increased time immobile. AChE activity was significantly reduced in cockroaches across all the groups when compared to the control. There was no significant alteration in GST activity and total thiol levels. It could be that both NaCl and MSG potentiates the neurotoxic effect of MeHg in cockroaches.