Browsing by Author "Farombi, E. O."

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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 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.
Adverse effects of In-Vitro cadmium exposure on quality and antioxidant enzyme status of Boar Spermatozoa
(University of Ibadan, 2014) Akinrinde, A. S.; Ojo, O. O.; Eboh, A. S.; Adedara, I. A.; Farombi, E. O.
This study was aimed to evaluate the reproductive toxicity of cadmium chloride (CdCl2. 2.5H2O) in Boar spermatozoa in vitro. Boar spermatozoa obtained from the caudal epididymis of freshly slaughtered boars and dispersed in semen incubation medium (containing tris-hydroxymethyl-aminomethane, citric acid and fructose) were incubated at four different concentrations (0, 0.5, 1.0 and 2.0mM) for 3 hours at 37OC. Sperm viability, motility and percentage of abnormal spermatozoa were assessed by microscopy every one hour during the 3–hour incubation period, using aliquots from the incubated samples. Samples thus treated with cadmium chloride were centrifuged and the supernatant was used in the assessment of biochemical parameters of oxidative stress including hydrogen peroxide (H2O2), reduced glutathione (GSH) and Lipid peroxidation. The activities of antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), Glutathione peroxidase (GPX) as well as transaminases (ALT and AST) and alkaline phosphatase (ALP) were also assessed. The percentage of motile and viable spermatozoa decreased significantly (p<0.05) after exposure of spermatozoa to CdCl2 in a concentration- and time-dependent manner. Cadmium significantly increased (p<0.05) the levels of H2O2 and malondialdehyde (MDA) in the spermatozoa with significant reductions (p<0.05) in the activities of SOD, GPX, and CAT. Slight but insignificant increase in GSH concentration was accompanied with a slight increase in GST activity. ALT, AST and ALP activities were differentially modified. The results of this study revealed that cadmium chloride caused reductions in sperm motility and viability, induction of oxidative stress and impairment of antioxidant enzyme activities.
Adverse effects of In-Vitro cadmium exposure on quality and antioxidant enzyme status of Boar Spermatozoa
(College of Medicine, University of Ibadan, 2014) Akinrinde, A. S.; Ojo, O. O.; Eboh, A. S.; Adedara, I. A.; Farombi, E. O.
This study was aimed to evaluate the reproductive toxicity of cadmium chloride (CdCl2. 2.5H2O) in Boar spermatozoa in vitro. Boar spermatozoa obtained from the caudal epididymis of freshly slaughtered boars and dispersed in semen incubation medium (containing tris-hydroxymethyl-aminomethane, citric acid and fructose) were incubated at four different concentrations (0, 0.5, 1.0 and 2.0mM) for 3 hours at 370C. Sperm viability, motility and percentage of abnormal spermatozoa were assessed by microscopy every one hour during the 3–hour incubation period, using aliquots from the incubated samples. Samples thus treated with cadmium chloride were centrifuged and the supernatant was used in the assessment of biochemical parameters of oxidative stress including hydrogen peroxide (H2O2), reduced glutathione (GSH) and Lipid peroxidation. The activities of antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), Glutathione peroxidase (GPX) as well as transaminases (ALT and AST) and alkaline phosphatase (ALP) were also assessed. The percentage of motile and viable spermatozoa decreased significantly (p<0.05) after exposure of spermatozoa to CdCl2 in a concentration- and time-dependent manner. Cadmium significantly increased (p<0.05) the levels of H2O2 and malondialdehyde (MDA) in the spermatozoa with significant reductions (p<0.05) in the activities of SOD, GPX, and CAT. Slight but insignificant increase in GSH concentration was accompanied with a slight increase in GST activity. ALT, AST and ALP activities were differentially modified. The results of this study revealed that cadmium chloride caused reductions in sperm motility and viability, induction of oxidative stress and impairment of antioxidant enzyme activities.
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.
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.
Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural biflavonoid of garcinia kola seeds
(Lippincott Williams & Wilkins, 2005) Farombi, E. O.; Adepoju, B. F.; Ola-Davies, O. E.; Emerole, G. O.
The chemopreventive effects of kolaviron, a natural antioxidant biflavonoid from the seeds of Garcinia kola, on aflatoxin B1 (AFB1)-induced genotoxicity and hepatic oxidative damage was investigated in rats. Kolavironmadministered orally at a dose of 200 mg/kg once a day for the first 2 weeks and then 100 mg/kg twice a day for the last 4 weeks of AFB1 (2 mg/kg, single dose, intraperitoneal) treatment reduced the AFB1-increased activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and gamma glutamyltransferase (c-GT) by 62%, 56% and 72% respectively. Malondialdehyde (MDA) formation and lipid hydroperoxide (LHP) accumulation were observed in the livers of AFB1-treated rats. Kolaviron significantly reduced the AFB1-induced MDA and LHP formation. Vitamins C and E were protective in reducing the increase in the activities of AST, ALT and c-GT as well as lipid peroxidation caused by AFB1 (P < 0.01). Administration of rats with kolaviron alone resulted in significant elevation in the activities of glutathione S-transferase, uridyl glucuronosyl transferase and NADH:quinone oxidoreductase by 2.45-, 1.62- and 1.38-folds respectively. In addition, kolaviron attenuated the AFB1-mediated decrease in the activities of these enzymes (P < 0.01). Pretreatment of rats with kolaviron, vitamins C and E alone did not exert genotoxicity assessed by the formation of micronucleated polychromatic erythrocytes (MNPCEs) (P> 0.05). Co-treatment of rats intraperitoneally with kolaviron (500 mg/kg) 30 min before and 30 min after AFB1 (1 mg/kg) administration inhibited the induction of MNPCEs by AFB1 (P < 0.001) after 72 h. While vitamin C was effective in reducing AFB1- induced MNPCEs formation, vitamin E did not elicit any antigenotoxic response. These results indicate kolaviron as effective chemopreventive agent against AFB1-induced genotoxicity and hepatic oxidative stress. Thus kolaviron may qualify for clinical trial in combating the menace of aflatoxicosis in endemic areas of aflatoxin contamination of foods.
Chemopreventives: untapped genii that compromise the science of the killer
(Ibadan University Press, 2016) Farombi, E. O.
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.
Dietary protocatechuic acid abrogates male reproductive dysfunction in streptozotocin-induced diabetic rats via suppression of oxidative damage, inflammation and caspase-3 activity
(Elsevier B.V., 2019) Adedara, I. A. || || || || ||; Okpara, E. S.; Busari, E. O.; Omole, O.; Owumi, S. E.; Farombi, E. O.
Clinical and experimental studies demonstrated that reproductive dysfunction is a non-lethal complication of diabetes. Protocatechuic acid (PCA) reportedly elicited several pharmacological effects in diabetic animals. However, there is paucity of information on the role of PCA in reproductive dysfunction associated with diabetes. The present study investigated the influence of PCA on the functional changes along the hypothalamicpituitary-testicular axis in male diabetic rats. Streptozotocin (STZ)-induced diabetic rats were orally treated with PCA at 25 and 50 mg/kg body weight for 45 consecutive days. Results showed that PCA treatment significantly dwindled blood glucose level as well as prevented diabetes mediated decrease in body weight gain and organosomatic indices of the testes and epididymis in the treated rats. Moreover, PCA increased the reproductive hormone levels, marker enzymes of testicular function and sperm functional characteristics in the treated rats. Further, PCA augmented the antioxidant status, inhibited lipid peroxidation and suppressed pro-inflammatory biomarkers including myeloperoxidase (MPO) activity, nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels as well as caspase-3 activity inhypothalamus, testes and epididymis of diabetic rats. Collectively, PCA effectively abrogated reproductive deficits in diabetic rats via mechanisms involving suppression of oxidative stress, inflammation and caspase-3 activity along with enhancement of sperm functional parameters. Thus, PCA may preserve reproductive health in humans suffering from diabetes.