Solomon E. Owumi

In vitro studies to assess the antioxidative, radical scavenging and arginase inhibitory potentials of extracts from Artocarpus altilis, Ficus exasperate and Kigelia africana

OBJECTIVE To justify the use of Artocarpus altilis (A. altilis), Ficus exasperata (F. exasperata) and Kigelia africana (K. africana) in ethnomedicine for the treatment of several ailments and to evaluate the in vitro antioxidant, radical scavenging and arginase inhibitory potentials of these herbs and compared with catechin (Standard). METHODS Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide, hydrogen peroxide (H2O2) and hydroxyl (OH) radicals scavenging methods. The flavonoids and phenolics content, inhibition of arginase activity, Fe(2+)/ascorbate-induced lipid peroxidation (LPO) and reducing power were also determined. RESULTS The A. altilis, F. exasperata and K. africana showed dose-dependent and significant scavenging of DPPH, H2O2 and OH radicals in vitro relative to catechin. The A. altilis and F. exasperata effectively scavenged DPPH radical with IC50 of 593 and 635 µg/mL and, OH radical with IC50 of 487 and 514 µg/mL, respectively. The DPPH and OH radicals scavenging activities followed the order A. altilis>F. exasperata>K. africana. In addition, A. altilis and F. exasperata significantly (P<0.05) inhibited LPO in a dose-dependent manner. The A. altilis extract had the most potent inhibitory activity against LPO with 79% relative to catechin (28%) at 750 µg/mL. The reducing power followed the order: A. altilis>Catechin>F. exasperata>K. africana at 1 000 µg/mL. The A. altilis at 500 and 750 µg/mL significantly (P<0.05) inhibited arginase activity by 63% and 67%, respectively. The flavonoids contents were found to be highest in A. altilis. CONCLUSIONS Extracts of A. altilis and F. exasperata are potent antioxidative agents with strong radical scavenging activity and inhibition of lipid peroxidation.

Co-administration of sodium arsenite and ethanol: Protection by aqueous extract of Aframomum longiscapum seeds.

Background: Human exposure to arsenicals, its toxicity, subsequent adverse effects on health has been widely reported and implicated in the etiology of several cancers. Objectives: We investigated the effect of Aframomum longiscapum (AL) extracts on sodium arsenite (SA) and ethanol (EtOH)-induced toxicities in rats. Materials and Methods: Male rats were fed SA, EtOH, and SA + EtOH, with or without AL for 5 weeks. Hepatic transaminases were assessed in serum, micronucleated polychromatic erythrocytes (mPCEs) from bone marrow, liver histopathology, and semen quality from caudal epididymis were assessed, respectively, and data were represented as mean ± SD, analyzed by ANOVA. Results: SA, SA + EtOH, and AL alone induced mPCEs formation in rat bone marrow (P < 0.05). A decrease (P < 0.05) in mPCEs in AL + SA + EtOH-treated rats compared with SA, and SA + EtOH was observed. SA and EtOH treatment increased serum hepatic transaminases (P < 0.05) relative to control, while AL treatment resulted in a decrease (P < 0.05). AL, SA, and SA + EtOH treatment decreased sperm count and motility (P < 0.05) with no effect on viability compared with control. Semen morphological abnormalities showed no difference (P > 0.05) across the treated groups. Hepatic histopathology indicated mild mononuclear cellular infiltration in the control group. Necrotic hepatocyte were observed in SA, SA + EtOH treated groups, with no visible lesions seen in the AL treated group. Mild hepatocyte congestion of the portal vessels was observed in AL + SA + EtOH-treated groups. Conclusion: The AL extract exhibited anticlastogenic and hepatoprotective potentials, reduced sperm count, motility, with no effect on viability and morphology. Our findings suggest that AL may mitigate the effect of arsenicals-induced clastogenicity implicated in chemical carcinogenesis.

Evaluation of hepatotoxicity and clastogenicity of carbofuran in male Wistar rats

Carbofuran based pesticides have gained wide usage in Nigeria recently. Consequently, animals and human populations are exposed to them in the environment. Information on in vivo toxicity of carbofuran in experimental models is scanty. The present study therefore examined the hepatotoxicity and clastogenic effects of carbofuran in rats. Male Wistar rats were exposed to carbofuran (p.o) at 0-5mg/kg bw for 5weeks. Carbofuran induced significant (p<0.05) increase in the serum activity of gamma-glutamyltransferase when compared with the negative control, but not activity of serum alanine and aspartate aminotransferases. It also significantly (p<0.05) induced micronucleated polychromatic erythrocytes formation in the bone marrow as compared with the control. The level of induction is dose dependent in both cases. In addition, there was significant (p<0.05) higher number of hepatic cells in the cell/mm(2) assay for the group treated with carbofuran. Histopathological analysis of liver samples from the treated groups revealed lesions ranging from general congestion (portal, central venous and sinusoidal), mild periportal cellular infiltration, diffused sinusoidal congestion and hepatic necrosis to severe congestion. Findings from this study suggest that carbofuran has clastogenic and hepatotoxic effects in rats. It therefore may constitute an environmental health risks in individuals so exposed.

Depletion of Kupffer cells modulates ethanol‐induced hepatocyte DNA synthesis in C57Bl/6 mice

Kupffer cells (KCs) are important in hepatic homeostasis and responses to xenobiotics. KCs are activated on interaction with endotoxin, releasing cytokines, and reactive oxygen species normally associated with increased gene expression, cellular growth, or hepatic injury. Ethanol‐induced endotoxemia is one means of KC activation. We propose that KC depletion attenuates the effect of EtOH‐induced endotoxemia to impact the hepatic growth response. Hepatic DNA synthesis was examined in KC competent (KC+) or KC‐depleted (KC−) C57BL/6 mice fed EtOH‐containing diet in the presence or absence of polyphenol‐60 antioxidant. KC depletion was assessed by F4/80 antigen, and DNA synthesis was assessed by 5‐bromo‐2′‐deoxyuridine incorporation. Tumor necrosis factor alpha (TNF‐α) messenger RNA released was quantified by RT‐PCR/electrophoresis. ERK1/2 phosphorylation was evaluated by Western blotting, and Nrf2 and CYP2E1protein were also assayed. Apoptosis and hepatic injury were examined by the Tunnel assay and hepatic transaminases in serum, respectively. Hepatic transaminases in serum (AST and ALT) were within normal range. Over 90% of KC was depleted by clodronate treatment. KC depletion decreased TNF‐α mRNA release, ERK1/2 phosphorylation, and hepatocyte DNA synthesis. KC depletion is associated with increased numbers of apoptotic cells bodies in KC− mice. Antioxidant treatment decreased DNA synthesis, Nrf2, and CYP2E1 protein expression in EtOH‐consuming mice. Our data indicate that upon ethanol exposure, KC participates in hepatic DNA synthesis and growth responses. Collectively, these observations suggest that KC depletion attenuates the downstream effect of ethanol‐induced endotoxemia by reduced cytokine and reactive oxygen species production with its concomitant effect on MAPK‐signaling pathway on hepatocyte DNA synthesis.

Protective effect of Juglans nigra on sodium arsenite-induced toxicity in rats

Background: Consumption of arsenic contaminated water has been implicated in metalloid-induced carcinogenesis. Dietary intake of certain plant products with chemoprotective properties may protect against the onset of diseases and promote maintenance of health. Objectives: We investigated the outcome of black walnut Juglans nigra (JN) consumption on sodium arsenite (SA)-induced toxicity in rats. Materials and Methods: Wister albino rats were treated as follows: Control, SA only (positive control) (2.5 mg/kg body weight), JN only (100 mg/kg weight), and JN+SA coadministered. After 5 weeks animals were sacrificed whole blood, femur, liver and testis harvested were assessed for hepatic transaminases and clastogenicity. Histology of the liver, sperm morphology and quality were also assessed. Data were analyzed (ANOVA) and expressed as means ±SD. Results: SA treatment elevated hepatic transaminases level in serum (P < 0.05), induced histological changes in liver: fibroplasia and periportal hepatocytes infiltration by mononuclear cells. These changes were ameliorated by JN (P < 0.05) coadministration. SA induced micronuclei formation (P < 0.05). Again JN decreased (P < 0.05) micronuclei formation by 50%. Sperm count and motility decreased (P < 0.05) in all groups compared to control. Conclusion: JN showed no protection against arsenite effect on sperm quality. Hepatoprotective and anticlastogenic effects were apparent suggesting a chemopreventive potential active against arsenite genotoxicity and chromosomal instability which have implication for metalloid-induced carcinogenesis.

Determination of metal ion contents of two antiemetic clays use in Geophagy

Nausea is usually associated with early to late stages of pregnancy. Geophagy-deliberate consumption of soil is a common method of managing gravidae-induced discomfort. To control nausea, pregnant women in Nigeria commonly eat baked clay called “Eko” and another type of clay that induces buccal constriction called “Omumu”. The metal contents in Eko and Omumu, digested under different pH conditions (acidic, alkaline and neutral), were investigated using Inductively Coupled Plasma Optical Emission Spectroscopy (ICPS-OES). We identified and quantitate the elements present and speculate on their potential impact on maternal and fetal health upon gestational exposure beyond the acceptable exposure levels and the Millennium Contaminant Level Goals (MCLG) set by the United States Environmental Protection Agency (USEPA). Specifically, our result indicates unacceptably high levels of aluminum in Eko and Omumu (>10-fold greater than the highest desirable levels set by the USEPA). The aluminum concentrations were influenced by the pH condition in which the samples were digested. Dietary exposure to aluminum at such high levels may be deleterious to maternal health and fetal development. Therefore consumption of Eko and Omumu as an antidote to reduce nausea during pregnancy should be discouraged. Future studies are planned to investigate specific impacts on fetal and maternal health and likely teratogenicity in rodent models.

Toxicological and phytoprotective effect of Keayodendron bridelioides and Monodora myristica extracts in Wister rats.

Objectives: The potential toxicity of Keayodendron bridelioides (KB), Monodora myristica (MM) were examined, and phytoprotection of MM and KB stemming from their phytochemical contents against sodium arsenite (SA) induced clastogenicity in Wister′s rat. Materials and Methods: Dose range studies of KB in rats, genotoxicity of MM and KB by SOS-inductive respomse were investigated using E. coli PQ37. Male rats were exposed to varying concentrations of MM, KB over a five week period to evaluate MM and KB phytoprotectives properties were also evaluated against sodium arsenite induced micronucleated erythrocytes, hepatotoxicity and sperm quality and morphology. Results: In contrast to KB, MM induced micronuclei formation in rat erythrocytes, MM and KB were however not genotoxic. MM, SA alone and in combination were hepatotoxic, characterized by elevated hepatic transaminases. Hepatoxicity were ameliorated by co-administration of KB (P < 0.05). MM and KB did not induce changes in semen morphology (P > 0.05); but decreased sperm count and motility (P < 0.05). Extracts exhibited anti-clastogenic (KB > MM), hepatoprotective (KB > MM) activities and maintained semen viability against SA treatment. Conclusion: Finding applications as herbal medicinal and food components KB and MM may be useful in mitigating the effect of toxicants in biological systems susceptible to oxidative damage.

Methyl jasmonate reduces testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats

BACKGROUND Phytotherapy is becoming a treatment option in management of diseases including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH, however the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. METHODS BPH was induced by daily injections of testosterone propionate (TP) (3mg/kg) for 28 days. RESULTS The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers; prostatic myeloperoxidase and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immuno-histochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax were seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory indices and induced apoptotic parameters in BPH rats. CONCLUSION MeJA protects against TP-induced BPH via mechanisms that involve anti-inflammation, induction of apoptosis and inhibition of phase I drug metabolizing enzyme.

Abstract A007: Methyl jasmonate and finasteride synergistically reduce testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats

Background: Phytotherapy is becoming a treatment option in management of diseases, including benign prostatic hyperplasia (BPH). We have shown previously that methyl jasmonate (MeJA) ameliorated BPH; however, the underlying mechanism of action remains unknown. This study was designed to investigate in mechanistic terms the protective role of MeJA in BPH. Methods: BPH was induced by daily injections of testosterone propionate (TP) (3 mg/kg) for 28 days. Results: The weight and organo-somatic weight of prostate in BPH rats were 6.8 and 5.1 times higher than castrated-control group, respectively. Inflammatory markers, prostatic myeloperoxidase,and total nitric oxide were significantly increased in BPH group. The activity of aniline hydroxylase (Phase I drug metabolizing enzyme) was significantly increased in BPH rats by 22%. In BPH group, immunohistochemistry revealed strong expression of prostatic inducible nitric oxide synthase, cyclooxygenase-2 and Bcl2, while mild expression of p53 and Bax WAS seen. Serum triglyceride and total cholesterol were significantly increased, while HDL-c was decreased in BPH. Interestingly, MeJA and finasteride (singly or combination) attenuated inflammatory and apoptotic indices in BPH rats. Conclusion: MeJA and finasteride synergistically protect against TP-induced BPH via mechanisms that involve antiinflammation, induction of apoptosis, and inhibition of phase I drug metabolizing enzyme. Citation Format: Oluwatosin A. Adaramoye, Solomon E. Owumi, Olubukola Akanni, Oluwabunmi E. Olapade-Olaopa, Olusoji J. Abiola, Oluyemi Akinloye. Methyl jasmonate and finasteride synergistically reduce testosterone-induced benign prostatic hyperplasia through regulation of inflammatory and apoptotic processes in rats [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A007.

Isoniazid Induced Toxicities and Idiosyncratic Responses in Male Albino Wistar Rats

Isoniazid (INH) is an anti-tuberculosis drug administered over a long period. Upon metabolism in the liver, INH generates nitrogen-centered radicals, reacting with cellular macromolecules, and induces toxic and transformational changes in cells and tissues. Here we examined the side effects of long-term (chronic) administration of isoniazid (2.5 and 5mg/kg) once daily for 30, 60 and 90 days consecutively: on hepatic transaminases, histological changes in hepatocytes and induction of micronuclei in the bone marrow and possible genotoxicity in E. coli PQ37. In addition, blood glucose was monitored during the various treatment period. Biochemical analysis of hepatic transaminases (I³ -glutamyl-, alanine amino-, aspartate aminotransferases and alkaline phosphatase) in INH treated group was significantly (p 0.05) in GST in both treatment groups at day 60. There was also a significant increase ( p <0.05) in the activity of superoxide dismutase activity. Micronucleus analysis further revealed an induction of micronucleated polychromatic erythrocytes (mPCEs), which was significant ( p <0.05) for both treatment doses at days 30, 60 and 90 respectively. In addition, INH genotoxicity assessed by UMU chromotest indicated that the 5mg/kg dosage has an induction ratio above the genotoxicity threshold of 1.5 suggesting genotoxicity in E.coli PQ37. Taken together, INH treatment at both doses (2.5 and 5mg/kg body weight) was hepatotoxic and induced nephrotoxic damages, in addition to mutagenic effect which is more pronounced at 2.5mg/kg dose, thereby suggesting dose-dependent cellular and genetic toxicity.