Biochemistry

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POST-JUNCTIONAL ALPHA ADRENOCEPTORS IN THE ANOCOCCYGEUS MUSCLE AND VAS DEFERENS: A COMPARATIVE STUDY IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
(1984-06) ADENEKAN, O. O.
The characteristics of the post-junctional α-adrenoceptors in the isolated anococcygeus muscle and vas deferens were compared in spontaneously hypertensive rats (SHR) and normotensive rats (NCR). Responses to α —adrenoceptor agonists were obtained in the absence and presence of cocaine and of antagonists. Noradrenaline (NA) and phenylephrine (PE) produced concentration related contrations of the preparations which were antagonised by phentolamine, prazosin and yohimbine in both rat strains, indicating α -adrenoceptor mediation. The effects of cocaine revealed the relative efficiency of the uptake mechanism in each preparation. In the anococcygeus NA was equipotent in the NCR and SHR in the absence of cocaine whereas it was less potent in the SHR in the presence of cocaine, PE was less potent in the SHR in the absence and presence of cocaine. Antagonism was assessed by pA2 and K(diss) determinations. Potencies were compared only when antagonism was competitive in both strains. In the anococcygeus low concentrations of prazosin (L-Praz) non—competitively antagonised NA but antagonised PE equally and competitively in both strains. Higher concentrations (H-Praz) competitively antagonised NA in both strains. Phentolamine was competitive against NA in NCR and against PE in both strains. However, it was non-competitive against NA in SHR, Low concentrations of yohimbine (L—YOH) competitively antagonised NA and PE in both the NCR and SHR but the K(diss) values were significantly different. Higher concentrations (H—YOH) was competitive against NA in the NCR and PE in both strains. In the vas L-Praz competitively antagonised both NA and PE in the NCR but gave non—competitive antagonism of both strains in the SHR, Phentolamine antagonised NA competitively in the NCR but non-competitively in the SHR. It was equipotent and competitive against PE in both strains. L—YOH non-competitively antagonised NA and PE in the NCR but in the SHR it was competitive. H-YOH antagonism was non—competitive against both NA and PE in both strains. It is suggested that there might be both the α1— and α2 post—junctional adrenoceptor in the NCR anococcygeus muscle, Prazosin and yohimbine seem to be able to differentiate between the two receptor subtypes at low concentrations, It is suggested further that the α2- subpopulation might not possess identical characteristics in the NCR and SHR anococcygeus. Also, there might be an alteration in NA uptake properties in the SHR, In the NCR vas deferens there seems to be a predominance of post-junctional α1-adrenoceptors. In the SHR vas, there might be an increase in the post-junctional α-adrenoceptor population and/or sensitivity. Furthermore, it seems that the post—junctional α2-adrenoceptor characteristics are somewhat different in the SHR, Uptake1 is suggested to be less efficient in the SHR vas.
SOME CONSEQUENCES OF THE BINDING OF AFLATOXIN B1 WITH PLASMA MEMBRANE ON THE REGULATION OF INTRACELLULAR Ca2+ HOMEOSTASIS
(1992-03) ADEBAYO, A. O.
The possible influence of aflatoxin B1 a potent hepatocellular carcinogen on the regulation of intracellular Ca2+ homeostasis has been studied using the red cell as a model. Preliminary work on the interaction of the toxin with the red cell membrane using spectrofluometric analysis indicated that the toxin binds spontaneously and irreversibly to the red cell membrane. The binding is highest at pH 4 and least at pH 10. Results obtained from studies using equilibrum dialysis technique show that about 4 nmoles of the toxin bind to one microgram membrane protein. Although the exact membrane component to which aflatoxin B1 binds is not known, experiments carried out to determine the influence of aflatoxin B1 on the activity of the calcium pumping protein revealed that the toxin inhibited the calmodulin-stimulated erythrocyte membrane Ca2+ -ATPase activity by about 50 percent, while it has little or no effect on its basal activity. Kinetic analysis of the inhibition shows that, the toxin reduces the Vmax and Km of the calmodulin-stimulated enzyme by 50 percent in a non-competitive manner, On the other hand, the carcinogen had no significant influence on the kinetic parameters of the enzyme in the non-activated state. Similar results were obtained for the triton X-100 solubilized and calmodulin affinity chromatographed enzyme. In this instance aflatoxin B1 inhibited the calmodulin-stimulated purified enzyme by 50 percent with or without preincubation on ice for half an hour. Again, the toxin had little or no effect on the basal activity of the enzyme in the absence of calmodulin. Analysis of the results obtained using varying concentrations of ATP shows that the Km and Vmax of the non-activated enzyme were not altered by the toxin while both the Vmax and Km values were reduced by about 50 percent in the presence of calmodulin. In addition aflatoxin B1 inhibited Diphosphotidyl glycerol (cardiolipin) by about 28% while it has no effect on the basal activity of the enzyme. Although, the inhibition of the membrane bound or purified Ca2+ ATPase by the toxin is concentration dependent, varying concentrations of phosphatidyl serine and phosphatidyl choline do not affect the inhibition of the purified enzyme by afla toxin B1. Results obtained with triton X-100 solubilized enzyme shows that triton X-100 alone could not activate the enzyme. Thus at triton X-100: protein ratio of 2, the enzyme was stimulated by calmodulin. This activity was sensitive to inhibition by the toxin. In this instance, the calmodulin-stimulated activity was inhibited by about 50%, while at lower ratios of the triton X-100 to protein there was no significant inhibition of enzyme. Results of experiments carried out on the 124KDa fragment, which was produced as a result of exposure to calpain a Ca2+ - dependent cysteine protease, indicated that the toxin has no effect whatsoever on the activity of the fragmented enzyme, Similarly experiments on limited proteolysis of the Ca2+ ATPase by trypsin to give the 90KDa fragment which still retains its calmodulin binding domain and the 76KDa fragment which has lost its calmodulin binding domain revealed that the aflatoxin inhibited the 90KDa fragment by about 50% while the 76KDa fragment is not affected at all. Altogether, -these findings show that aflatoxin B1 inhibits the plasma membrane Ca2+ - pumping ATPase by interacting with the enzyme at the calmodulin binding domain. The nature of the exact amino acid residue to which the toxin binds is however not known. The implication of these observations is that Ca2+ extrusion may be hampered in situations where the cell is poisoned by the aflatoxin
THE MODULATION OF RAT LIVER MICROSOMAL CALCIUM ION-PUMPING ATPase BY DICOPHANE AND LOW PROTEIN INTAKE
(1992-05) ADENUGA, G. A.
The effects of the liver tumour promoter, dicophane, with those of low protein intake (LPI) on the functional expression of rat liver microsomal Ca(2+) -ATPase were compared. The effects of dicophane and LPI on the activity of the microsomal enzyme after carcinogenic initiation by pretreatment with aflatoxin B (AFB), a genotoxic liver carcinogen, were also compared. The Status of membrane - bound Ca(2+) -ATPase of erythrocytes of humans having primary liver cancer (PLC) and kwashiorkor was assessed. The specific activity of membrane - bound microsomal Ca(2+) -AT Pase of the livers of untreated rats was 4.543 ± 0.857 µmole P/mg protein/hr. at pH 8.0 and was insensitive to calmodulin. The specific activity of the enzyme was significantly decreased (P < 0.01) following subcutaneous administration of a single dose of 75mg dicophane/kg body wt.; the affinity of the enzyme for Ca(2+) was however unaffected. Similarly, liver microsomal Ca (2+)-ATPase activity was significantly diminished following the ingestion of low protein diet by rats for 12 weeks. The mean Ca(2+) -ATPase activity of AFB -treated animals (in the absence of dicophane) was not significantly different (P > 0.05) from that of AFB-treated rats which subsequently received dicophane. In contrast, liver microsomal Ca(2+)-ATPase activity of animals fed low protein diet prior to and after AFB ingestion was higher (P < 0.05) than that of animals which were on low protein diet only. Basal activity of erythrocyte Ca(2+) -ATPase in paediatric controls and those having kwashiorkor (protein-energy-malnutrition) were similar (P > 0.05); similar observations were made between normal adults and those suffering from PLC. Erythrocyte Ca(2+) -ATPase of either PLC or kwashiorkor patients was however, some- what, less sensitive (15-40 %) to the stimulatory effect of calmodulin, an endogenous activator of the Ca(2+) -pump. These results suggest that liver microsomal Ca(2+) -ATPase could be a useful biochemical marker to determine the onset or occurrence of tumour promotion in liver cells. Finally, chronic dietary protein malnutrition mimics the effect of chemical liver tumour promoters and could possibly enhance the development of human PLC particularly n those areas of the tropics where malnutrition is prevalent. Future confirmatory experiments are however re-quired to fully justify this postulate.
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.
Evaluation of antioxidant properties of Mallotus oppositifolium in in-vitro, in-vivo and ex-vivo model systems
(College of Medicine, University of Ibadan, 2010) Adedara, I. A.; Adesanoye, O. A.; Farombi, E. O.
The protective effect of antioxidants and naturai !y occurring substances against oxidative stress damage has recently attracted much attention. The ieaves of Mallotus oppositifolium, a shrub of thè famìly Euphorbiacea that grows in many parts of Africa, are used in folk medicine and herbal preparations for die treatment of dysentery, worms and malaria. The study in vestigated thè antioxidant properties of thè methanolic extract of thè Ieaves of Mallotus oppositifolium (MEMO) in comparison with butylated hydroxyl anisole (BHA) as a standard antioxidant using three free radicai generators viz hydrophilic radicai generator 2,2-azobis(2- amidino propane) dihydrochloride (AAPH), hydrophobic radicai generator 2,2-azobis(2,4-dimethylvaleronitrile) (AMVN) and hydroxyl radicai and non-specific radicai generator Fe2+/ascorbate System in an in vitro, in vivo and ex-vivo model systems. Phytochemical analysis of thè Ieaves extract was al so assessed. Phytochemical analysis of thè powdered Ieaves revealed thè presence of alkaloids, tannins, cardenolides and saponins. In vitro study indicated that while MEMO failed to inhibit lipid peroxidation (LPO) induced by AAPH, while BHA offered 55.5% inhibition. In addition, while AMVN- induced LPO was inhibited by 17.7% and 29.4% by MEMO and BHArespectively, Fe2+/ascorbate system- induced LPO was inhibited by 57.9% and 78.9% by MEMO and BHArespectively. Ex-vivo studies showed that MEMO at lOOmg/kg bw reduced malondialdehyde and protein carbonyl levels by 34.5% and 12.0% respectively compared with thè control. In vivo, MEMO increased (P<0.05) superoxide dismutase and calai ase activities by 408.0% and 295.0% respectively. Taken together, this study demonstrates that MEMO exhibits antioxidant, radicai scavenging and enhancement of enzymatic antioxidant capacity and as such could intervene in toxicological processes mediated by free radicai mechanisms.
Role of oxidative stress in reproductive toxicity induced by co-administration of chloramphenicol and multivitamin–haematinics complex in rats
(Nordic societies for Pharmacology and Toxicology, 2010) Oyagbemi, A. A.; Adedara, I. A.; Saba, A. B.; Farombi, E. O.
Concurrent administration of chloramphenicol (CAP) with multivitamin–haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administration with MHC in male rats. CAP and MHC were administered orally at therapeutic doses of 28 mg ⁄ kg body-weight and 0.08 ml ⁄ kg body-weight, respectively, every 6 hr for 10 days. After exposure, while there was body-weight loss in CAP, MHC and CAP plus MHC-treated animals, there were no treatment-related changes in the absolute and relative weights of the testes in all treated groups. Alone, MHC treatment markedly decreased catalase (CAT), glutathione S-transferase (GST), and 5¢ nucleotidase (5¢ NTD) activities whereas it resulted in significant increase in superoxide dismutase (SOD) activity. Activities of SOD, CAT and GST as well as H2O2 levels were not significantly affected in CAP and CAP plus MHC-treated rats whereas GSH level and 5¢ NTD activity were markedly decreased in CAP plus MHC-treated rats. Significant increase in testicular alkaline phosphatase activity, lipid peroxidation and sperm abnormalities were accompanied by reduction in epididymal sperm number, sperm motility and live–dead ratio in all treatment groups whereas aminotransferase activities were unaffected. Treatment-related degeneration of the testes was evident in all treated animals. In summary, while MHC-induced testicular toxicity via oxidative stress, CAP did not and their combination is implicated in reproductive dysfunction within the time course of our investigation.
Induction of oxidative stress in liver and kidney of rats exposed to Nigerian bonny light crude oil
(Wiley Periodicals, Inc., 2010) Adedara, I. A.; Teberen, R.; Ebokaiwe, A. P; Ehwerhemuepha, T.; Farombi, E. O.
The local population of Niger-Delta in the Southern part of Nigeria have used bonny light crude oil (BLCO) as a remedy for various ailments and are exposed to some extent to this widespread environmental contaminant or its metabolites through the food chain. BLCO’s hepatorenal toxicity was studied using oxidative stress indices to elucidate the precise nature and mechanism of action. BLCO was orally administered at concentrations of 0, 200, 400, and 800 mg kg21 to adult male rats for 7 days. After exposure, kidney weight was unaffected, but liver weight decreased significantly at 800 mg kg21 only compared with control. BLCO exposure resulted in dose-dependent elevation of serum aminotransferases, total bilirubin, urea, and creatinine. Activities of superoxide dismutase and catalase decreased significantly, whereas c-glutamyltransferase activity and the level of glutathione increased significantly in BLCO-treated animals compared with control in both liver and kidney of rat. Renal activities of glucose-6- phosphatase and 50-nucleotidase markedly decreased in a dose-dependent manner in BLCO-exposed rats. In addition, the levels of hydrogen peroxide and lipid peroxidation significantly increased, dose dependently, in liver and kidney of BLCO-treated rats compared with control. BLCO-treated rats showed marked degeneration of kidney evident in cortical hemorrhages, tubular necrosis, protein casts, and cellular infiltration. However, no treatment-related liver histopathology was observed. The results suggested that BLCO elicits disruption of antioxidant status and concomitant elevation of hydrogen peroxide and lipid peroxidation differentially in liver and kidney of rats. The hepatorenal toxicity of BLCO could be due to induction of oxidative stress in liver and kidney.
Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats
(Elsevier GmbH., 2010) Adaramoye, O. A.; Adedara, I. A.; Farombi, E. O.
Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body _-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of _-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to _-radiation. Gamma-irradiation resulted in a significant (p < 0.05) decrease in body weight and relative testes weight. Also, _-irradiation significantly (p < 0.05) decreased the activities of superoxide dismutase, catalase and glutathione S-transferase as well as glutathione level, but markedly elevated malondialdehyde levels in the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (p < 0.05) decreased the body weight loss and increased relative testes weights of the rats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together,_-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity.
Influence of quercetin on haematological indices and biomarkers of oxidative stress in the serum of rats exposed to atrazine
(College of Medicine, University of Ibadan, 2010) Abarikwu, S. O.; Adedara, I. A.; Farombi, E. O.
The study was carried out to compare thè effects of quercetin (QT) at doses of 5mg/kg (QQ and lOmg/kg (Q|0) against thè hematological toxicity and oxidative stress caused by atrazine (ATR). Male rats were oraily gavaged with ATR at a dose of 120mg/kg for 16 days. Erythropenia, leucopenia was observed in ATR treated rats. Other hematological variables such as packed celi volume (PCV), hemoglobin concentration (HGB), mean celi hemoglobin concentration (MCHC), mean corpuscular volume (MCV), neulrophils (NEU), lymphocytes (LYM) and blood platelet (PLT) showed no significant change with respect to thè control values. The activities of thè antioxidant defense molecules including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) and glutathione (GSH) were decreased; malondialdehyde (MDA) level increased but catalase (CAT) activity showed no change.Co-administration of Q5 did not prevent thè oxidative stress and thè fiematological alterations caused by ATR. In these groups of animals, thè values of PLT and NEUT were increased while LYM decreased indicating more pronounce hematological changes. The changes in both thè biochemical and hematological variables were noi malized to thè control values on co-administration of Ql0. We suggest that thè antioxidant activities of QT al a doses of lOmg/kg could be responsible for its protecti ve effects against ATR-induced oxidative stress and hematological toxicity.
Induction of oxidative damage in the testes and spermatozoa and hematotoxicity in rats exposed to multiple doses of ethylene glycol monoethyl ether
(2010) Adedara, I. A.; Farombi, E. O.
The effects of ethylene glycol monoethyl ether (EGEE) on the antioxidant systems of the testes and epididymal spermatozoa were investigated in rats at dose levels of 0, 100, 200 and 400 mg kg–1 body weight (bw) administered orally by gavage for 14 consecutive days. The bw gain of the EGEE-treated rats decreased significantly at 200 and 400 mg kg–1 bw compared with the control group. There were no significant changes in the weights of the testes, epididymis, seminal vesicles and prostate glands of the EGEE-treated rats. In the testes, while EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities, it markedly increased the malondialdehyde (MDA) level, glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities at 200 and 400 mg kg–1 dose levels but vitamin C content remained unaffected in all the groups. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GST and LDH as well as in the levels of vitamin C and GSH but significantly increased the MDA level and SOD activity compared with the control rats. Histopathological examination showed severe degeneration of the testes, such as generalized erosion and necrosis of the germinal epithelium of the
Nigerian Bonny Light crude oil disrupts antioxidant systems in testes and sperm of Rats
(Springer Science, 2010) Farombi, E. O. || || || ||; Adedara, I. A.; Ebokaiwe, A. P.; Teberen, R.; Ehwerhemuepha, T.
Nigerian Bonny light crude oil (BLCO) is commonly used by the local population in folklore medicine
Tissues distribution of heavy metals and erythrocytes antioxidant status in rats exposed to Nigerian bonny light crude oil
(Sage Publishers, 2011) Adedara, I. A.; Ebokaiwe, A. P.; Farombi, E. O.
The harmful effects of folkloric uses of Nigerian bonny light crude oil (BLCO) in ailments management may outweigh the expected beneficial effects. We investigated the levels of heavy metal concentrations in the tissues as well as the effect of BLCO on the antioxidant status of erythrocytes of rats after oral exposure to 0, 200 and 800 mg/kg BLCO for 7 days. Analysis of heavy metal concentrations in BLCO showed that Zn > Fe > Pb > Cu > Ni. The trend of accumulation of the metals in the tissues is blood—Fe > Pb >Zn whereas Cu and Ni levels were not affected; Liver—Ni > Zn > Fe > Cu > Pb and Testes—Ni > Cu > Pb > Zn > Fe. The order of concentration of the metals in the tissues is as follows: iron—blood > liver > testes; zinc—liver > blood > testes; lead—blood > liver > testes; copper—testes > liver > blood; nickel—liver > testes > blood. Activities of the antioxidant enzymes of erythrocytes such as superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase increased significantly in a dose-dependent manner with significant elevation in hydrogen peroxide and malondialdehyde levels, whereas glutathione level was not significantly decreased in BLCO-treated animals. Collectively, the results showed that BLCO induces oxidative damage to erythrocytes of rats.
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.
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.
Lack of recovery from hepatic oxidative damage in rats treated with Nigerian bonny light crude oil
(John Wiley & Sons, Ltd., 2012) Adedara, I. A.; Farombi, E. O.
The use of Nigerian bonny light crude oil (BLCO) in the treatment of gastrointestinal disorders, burns, foot ulcers and reproductive capacity is a common practice in the southern part of Nigeria. Towards understanding the mechanism and the reversibility of hepatotoxicity induced by BLCO, adult male Wistar rats were orally administered with BLCO at 0, 50, 100 and 200 mg kg 1 for 21 days. One-half of the rats were sacrificed on day 22, whereas the remaining half stayed for an additional 21 days without treatment. Whereas the activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione S-transferase were significantly (p<0.05) increased, gamma glutamyl transferase activity was significantly decreased in a dose-dependent manner. The levels of glutathione, hydrogen peroxide and malondialdehyde were significantly elevated in BLCO-treated animals. In addition, hepatic degeneration was accompanied with elevation in serum aminotransferases activities without affecting bilirubin levels. Whereas most of the above-mentioned parameters were consistent in animals from withdrawal experiment, both total and conjugated bilirubin levels were significantly increased after 21 days of BLCO-treatment withdrawal. Taken together, BLCO-induced hepatotoxicity could be due to increased oxidative stress which was not reversible upon withdrawal of treatment within the time course of investigation in male rats.
Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats
(Elsevier B.V., 2013) Adedara, I. A.; Vaithinathan, S.; Jubendradass, R.; Mathura, P.P.; Farombi, E.O.
The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200 mg/kg) singly or in combi-nation with kolaviron (100 and 200 mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid con-centration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroido- genic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antiox- idant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.
Hepatic, testicular and spermatozoa antioxidant status in rats chronically treated with Garcinia kola seed
(Elsevier Ireland Ltd., 2013) Farombi, E. O.; Adedara, I. A.; Oyenihi, A. B.; Ekakitie, E.; Kehinde, S.
Ethnopharmacological relevance: Garciniakola seed is commonly used in African Traditional Medicineas a remedy for liver disorders, hepatitis, bronchitis, throat infections as well as an aphrodisiac and fertility enhancing substance. Owing to the abundance of complex mixture of phenolic compounds in Garciniakola seed, there is a growing safety concern on its long-term use in folklore medicine.The present study evaluated the hepatic, testicular and spermatozoa antioxidant status in rats chronically treated with Garciniakola seed. Materials and methods: Adult male Wistar rats were randomly assigned to four groups of 10rats each and were orally administered with Garciniakola at 0, 250, 500 and 1000mg/kg for 6 consecutive weeks. Clinical observations, serum biochemistry, oxidative stress biomarkers, spermatozoa parameters and histopathological examination of the organs were assessed to monitor treatment-related adverse effects in rats. Results: Long-term treatment of Garcinia kola had no adverse effect on the spermatozoa characteristics but significantly elevated testosterone concentration when compared to the control group. Improvement of antioxidant systems was accompanied by a significant decrease in malondialdehyde level in the liver, testes and spermatozoa of Garciniakola treated rats. Histological observation revealed that chronic administration of Garciniakola had no effect on the liver and testes at all doses when compared with control. Conclusion: Garciniakola seed boosts the antioxidant status and exhibits no adverse effect on the liver, testes and spermatozoa after a long-term oral exposure in rats.
Involvement of oxidative stress in municipal landfill leachate-induced toxicity in boar sperm
(Elsevier B.V., 2013) Adedara, I. A. || || || ||; Oyebiyi, O. O.; Lawal, T. A.; Adesina, A. A.; Farombi, E. O.
Exposure to leachates generated from an improperly managed hazardous waste dump sites is detrimental to human health and the ecosystem. The present study investigated the effect of Olushosun municipal landfill leachate (OMLL) on sperm characteristics and antioxidant systems in boar sperm cells. The sperm cells were incubated with the leachate at final concentrations of 0, 1, 2, 4 and 8% for 3 h at 37◦C. Sperm characteristics were monitored hourly during the incubation period whereas amino transferases activities and oxidative stress indices were determined after the incubation period. Results revealed a time- and dose-dependent decline in sperm progressive motility from 1 h post-treatment with 2, 4 and 8% OMLL whereas decreased sperm viability with elevated abnormalities were observed from2 h post-treatment with 4 and 8% OMLL when compared with control. Exposure to OMLL caused a significant increase in aminotransferases, catalase and glutathione-S-transferase activities whereas it markedly decreased superoxide dismutase and glutathione peroxidase activities without affecting glutathione level in the treated sperm cells. Co-incubation of sperm with OMLL increased the levels of hydrogen peroxide and malondialdehyde levels. In conclusion, OMLL elicited spermatotoxicity via induction of oxidative stress possibly generated through an enhanced intracellular reactive oxygen species.
Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis via down-regulation of stress proteins, Fas/Fas-L and caspases expressions in rats
(Informa Healthcare USA, Inc., 2013) Adedara, I. A.; Mathur, P. P.; Farombi, E. O.
This study investigated the protective role of kolaviron, a natural antioxidant biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats were exposed to EGEE (200 mg/kg) separately or in combination with either kolaviron (100 or 200 mg/kg) or vitamin E (50 mg/kg) for 14 days. Immunoblot analysis revealed that EGEE exposure alone significantly increased stress-inducible proteins levels. The increased protein expression of active caspases, Fas and Fas-L, was accompanied by nuclear factor kappa B downregulation and elevation of cytosolic cytochrome c level in EGEE-treated rats. In addition, the observation from immunofluorescence staining was consistent with the increased TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E significantly inhibited induction of stress proteins and germ cell apoptosis in EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti-apoptotic properties prevented EGEE-induced reproductive toxicity in rats.
Sperm characteristics, antioxidant status and hormonal profile in rats treated with artemisinin
(Blackwell Verlag GmbH, 2013) Farombi, E. O.; Adedara, I. A.; Abolaji, A. O.; Anamelechi, J. P.; Sangodele, J. O.
The indiscriminate use, abuse and patients’ noncompliance to normal prescription of artemisinin and its derivatives are a common practice during the treatment for drug-resistant malaria parasites in most developing countries. This study investigated the influence of artemisinin on the testicular and epididymal sperm antioxidant systems as well as on the plasma levels of hormones from the pituitary and thyroid components of the brain–pituitary–testicular axis. Oral exposure of rats to 0, 7 and 35 mg kg_1 artemisinin for 7 days showed that the testicular antioxidant status at both therapeutic dose (7 mg kg_1) and overdose (35 mg kg_1), and the sperm antioxidant status at therapeutic dose of artemisinin remained unaffected compared with control. However, increased hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant decrease in glutathione peroxidase and glutathione-S-transferase activities as well as glutathione level in spermatozoon of rats administered with overdose of artemisinin. While plasma levels of all the hormones investigated remained unaffected, severe epididymal degeneration with concomitant decrease in sperm quantity and quality was observed in rats treated with overdose of artemisinin compared with control. Overall, induction of oxidative stress in the epididymis, but not in the testes, could cause reproductive deficits in individuals unduly undergoing artemisinin therapy.