Heme Oxygenase-1 as a Potential Therapeutic Target for Hepatoprotection

Farombi, Ebenezer Olatunde,Surh, Young-Joon Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.5

Heme oxygenase (HO), the rate limiting enzyme in the breakdown of heme into carbon monoxide (CO), iron and bilirubin, has recently received overwhelming research attention. To date three mammalian HO isozymes have been identified, and the only inducible form is HO-1 while HO-2 and HO-3 are constitutively expressed. Advances in unveiling signal transduction network indicate that a battery of redox-sensitive transcription factors, such as activator protein-1 (AP-1), nuclear factor-kappa B (NF-${\kappa}B$) and nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases including mitogen-activated protein kinases play an important regulatory role in HO-1 gene induction. The products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin have been shown to exert protective effects in several organs against oxidative and other noxious stimuli. In this context, it is interesting to note that induction of HO-1 expression contributes to protection against liver damage induced by several chemical compounds such as acetaminophen, carbon tetrachloride and heavy metals, suggesting HO-1 induction as an important cellular endeavor for hepatoprotection. The focus of this review is on the significance of targeted induction of HO-1 as a potential therapeutic strategy to protect against chemically-induced liver injury as well as hepatocarcinogenesis.

Evaluation of Genotoxicity of Three Antimalarial Drugs Amodiaquine, Mefloquine and Halofantrine in Rat Liver Cells

Farombi E. Olatunde Korean Environmental Mutagen Society 2005 한국환경성돌연변이·발암원학회지 Vol.25 No.3

The genotoxic effect of antimalarial drugs amodiaquine (AQ), mefloquine (MQ) and halofantrine (HF) was investigated in.at liver cells using the alkaline comet assay. AQ, MQ and HF at concentrations between $0-1000{\mu}mol/L$ significantly increased DNA strand breaks of rat liver cells dose-dependently. The order of induction of strand breaks was AQ>MQ>HF. The rat liver cells exposed to AQ and HF (200 and 400 ${\mu}mol/L$) and treated with (Fpg) the bacterial DNA repair enzyme that recognizes oxidized purine showed greater DNA damage than those not treated with the enzyme, providing evidence that AQ and HF induced oxidation of purines. Such an effect was not observed when MQ was treated with the enzyme. Treatment of cells with catalase, an enzyme inactivating hydrogen peroxide, decreased significantly the extent of DNA damage induced by AQ, and HF but not the one induced by MQ. Similarly quercetin, an antioxidant flavonoid at $50{\mu}mol/L$ attenuated the extent of the formation of DNA strand breaks by both AQ and HE. Quercetin, however, did not modify the effects of MQ. These results indicate the genotoxicity of AQ, MQ and HF in rat liver cells. In addition, the results suggest that reactive oxygen species may be involved in the formation of DNA lesions induced by AQ and HF and that, free radical scavengers may elicit protective effects against genotoxicity of these antimalarial drugs.

Evaluation of Genotoxicity of Three Antimalarial Drugs Amodiaquine, Mefloquine and Halofantrine in Rat Liver Cells

E. Olatunde Farombi 한국환경성돌연변이발암원학회 2005 한국환경성돌연변이·발암원학회지 Vol.25 No.3

The genotoxic effect of antimalarial drugs amodiaquine (AQ), mefloquine (MQ) and<br/> halofantrine (HF) was investigated in rat liver cells using the alkaline comet assay. AQ, MQ and HF at concentrations between 0-1000 μmol/L significantly increased DNA strand breaks of rat liver cells dosedependently. The order of induction of strand breaks was AQ > MQ > HF. The rat liver cells exposed to AQ and HF (200 and 400 μmol/L) and treated with (Fpg) the bacterial DNA repair enzyme that recognizes oxidized purine showed greater DNA damage than those not treated with the enzyme, providing evidence that AQ and HF induced oxidation of purines. Such an effect was not observed when MQ was treated with the enzyme. Treatment of cells with catalase, an enzyme inactivating hydrogen peroxide, decreased significantly the extent of DNA damage induced by AQ, and HF but not the one induced by MQ. Similarly quercetin, an antioxidant flavonoid at 50 μmol/L attenuated the extent of the formation of DNA strand breaks by both AQ and HF. Quercetin, however, did not modify the effects of MQ. These results indicate the genotoxicity of AQ, MQ and HF in rat liver cells. In addition, the results suggest that reactive oxygen species may be involved in the formation of DNA lesions induced by AQ and HF and that, free radical scavengers may elicit protective effects against genotoxicity of these antimalarial drugs.

Falls and Their Associated Risks in Parkinson’s Disease Patients in Nigeria

Temitope Hannah Farombi,Mayowa O Owolabi,Adesola Ogunniyi 대한파킨슨병및이상운동질환학회 2016 Journal Of Movement Disorders Vol.9 No.3

Objective Falls are a devastating consequence of Parkinson’s disease (PD) and are due to motor imbalance. However, the frequency of falls and their risk factors among Nigerians with PD is not known despite the significant increase in PD cases in the country. To assess fall risk factors and frequency in Nigerian PD patients. Methods Using an analytical design to compare falling versus non-falling patients, 81 PD patients were assessed for clinical factors, frequency of falls, and candidate risk factors for falls according to the Tinetti Balance and Gait, Unified Parkinson’s Disease Rating Scale subsection 1, and Timed Up and Go Tests. Descriptive, bivariate, and multivariate analyses were performed at the 95% confidence level. Results The mean age of participants was 65.6 ± 9.7 years. Falls were about three times (p < 0.001) more common in PD patients. Of the falling patients, 67.7% sustained injuries, 67.7% had recurrent falls and 44.9% admitted to having a fear of falling. The independent statistical predictors of fall were fear of falling [odds ratio (OR): 3.86], disease severity (OR: 1.09) and disease duration (OR: 1.01). Conclusion The frequency of falls in PD patients was significantly higher when compared with the healthy adult population, and the modifiable predictor was fear of falling with a potential to significantly reduce falls when strategically addressed

Heme Oxygenase-1 as a Potential Therapeutic Target for Hepatoprotection Ebenezer Olatunde Farombi(Review)

Surh, Young-Joon,Farombi, Ebenezer Olatunde 한국생화학분자생물학회 (구 한국생화학회) 2006 BMB Reports Vol.39 No.5

Hepatoprotective Activity of Purified Fractions from Garcinia kola Seeds in Mice Intoxicated with Carbon Tetrachloride

O.A. Adaramoye,E.O. Farombi,M. Nssien,S.O. Idowu,O.G. Ademowo,E.O. Adeyemi 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.3

The hepatoprotective activity of kolaviron (KV), a biflavonoid complex from Garcinia kola seeds, and its purified fractions was investigated in mice intoxicated with carbon tetrachloride (CCl4). The ability of vitamin E to attenuate the toxicity was also examined. KV was extracted from powdered seeds of G. kola and then separated by thin-layer chromatography into three fractions—Fraction I (FI), Fraction II (FII), and Fraction III (FIII), with ratio of fronts values of 0.48, 0.71, and 0.76, respectively. Pretreatment with KV, FI, and FII at a dose of 100 mg/kg of body weight for 2 weeks and then challenge with CCl4 at a dose of 1.2 g/kg of body weight, three times a week for 2 consecutive weeks, decreased the CCl4-induced increase in activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by 31%, 30%, and 31% and 41%, 55%, and 42%, respectively. CCl4 intoxication also caused a significant (P < .05) accumulation of lipid peroxidation (LPO) products as revealed by the formation of the thiobarbituric acid-reactive substances: CCl4 induced LPO levels in serum and microsomes by 112% and 89%, respectively. However, pretreatment with KV, FI, and FII decreased LPO levels in serum by 31%, 41%, and 40% and in microsomes by 48%, 39%, and 35%, respectively. Vitamin E was protective in reducing the CCl4-induced increase in levels of AST, ALT, and γ-glutamyl transferase as well as LPO. Furthermore, CCl4 intoxication significantly (P < .05) decreased the activities of microsomal glucose-6-phosphatase, aniline hydroxylase, and cytosolic glutathione-S-transferase (GST). While pretreatments with KV, FI, and FII were able to ameliorate the levels of glucose-6-phosphatase and GST, there were no significant (P > .05) effects on the levels of aniline hydroxylase and DT-diaphorase. This study confirms that FI and FII from KV enhanced recovery from CCl4-induced hepatotoxicity by decreasing the extent of LPO and also inducing the levels of phase II enzyme (GST). These fractions are responsible for the observed antihepatotoxic effect of KV.

Evaluation of Antioxidant and Free Radical Scavenging Capacities of Some Nigerian Indigenous Medicinal Plants

Afolabi C. Akinmoladun,Efere M. Obuotor,Ebenezer O. Farombi 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.2

Methanolic extracts of 10 selected Nigerian medicinal plants—Psidium guajava, Alstonia boonei, Cassia alata, Newbouldia laevis, Spondias mombin, Globimetula cupulatum, Chromolaena odorata, Securidaca longepedunculata, Ocimum gratissimum, and Morinda lucida—widely used in ethnomedicine, were assessed for phytochemical constituents and antioxidant and free radical scavenging activities using seven different antioxidant assay methods. Phytochemical screening gave positive tests for steroids, terpenoids, and cardiac glycosides, alkaloids, saponins, tannins, and flavonoids contained in the extracts. P. guajava contained the highest amount of total phenolics (380.08±4.40mg/L gallic acid equivalents), and the highest amounts of total flavonoids were found in the leaf extracts of C. alata (275.16±1.62μg/mL quercetin equivalents [QE]), C. odorata (272.12±2.32μg/mL QE), and P. guajava (269.72±2.78μg/mL QE). Percentage 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was highest in S. mombin (88.58±3.04%) and P. guajava (82.79±2.84%) and compared with values obtained for ascorbic acid and gallic acid. All the extracts, generally, had low nitric oxide radical scavenging activities, and G. cupulatum had the highest hydroxyl radical scavenging activity (63.84±0.97%). The extracts in general demonstrated high lipid peroxidation inhibitory activity, with only M. lucida (38.74±1.99%) and A. boonei (47.16±0.59%) being exceptions. The reductive potential was highest in P. guajava (0.79±0.04) and least in S. longepedunculata (0.26±0.00). DPPH assay correlated well with total phenolic contents (r2=0.76) and reductive potential (r2=0.81) and fairly with lipid peroxidation inhibitory activity (r2=0.51). There was a good correlation between total phenolic contents and reductive potential (r2=0.79) and a fair correlation between total phenolic contents and lipid peroxidation inhibitory activity (r2=0.55). These results suggest that the methanolic extracts of the studied plant parts possess significant antioxidant and radical scavenging activities that may be due to the phytochemical content of the plants and as such make them potential candidates as natural chemoprophylactic agents. In addition, multiple assay methods should be used in comparing antioxidant capacities of samples to have a reliable result.