Anthony O. Uwaifo

The presence of aflatoxin and some polycyclic aromatic hydrocarbons in human foods

An analysis of several common food items (fish, meat, crops and spices) as sold in the Nigerian markets has shown the presence of (a) benzo[a]-pyrene and benz[a]anthracene in fish and meat samples, and (b) aflatoxin in crops and spices. These results are discussed in relation to the relatively high incidence of cancer in tropical Africa.

Mutagenicity of chamuvaritin: A benzyldihydrochalcone isolated from a medicinal plant

The mutagenic effects of chamuvaritin, dihydrobenzylchalcone isolated from Uvaria chamae, were investigated using Salmonella typhimurium tester strains TA92, TA94--98, TA100--1535, TA1537 and TA1538. The phytochemical was mutagenic in tester strains TA98 and TA100 and required activation by the hepatic S-9 microsomal enzyme preparation.

Toxicity associated with repeated administration of artemether-lumefantrine in rats.

Chemotherapy remains an important approach in the fight against malaria. Artemether–lumefantrine combination is widely in use due to its effectiveness against Plasmodium falciparum. Misuse in the form of multiple repeated doses of this anti‐malaria drug is rampant in Nigeria. This study was designed to assess the hepatotoxic and clastogenic potential of extreme misuse of artemether–lumefantrine in rats. Graded doses of artemether–lumefantrine (1–5 mg/kg body weight) were administered by oral gavage for 6 weeks, twice daily, for 3 consecutive days per week. Artemether–lumefantrine, at all doses, did not have significant effects on the body and relative liver weight of treated group compared to the negative control group. The mean γ‐glutamyltransferase, alanine, and aspartate aminotransaminase activity in groups of artemether–lumefantrine treated rats were significantly higher (p < 0.05) than that of the negative control group indicating that repeated administration of artemether–lumefantrine may be hepatotoxic. Findings from histological analyses of liver cross‐section support the enzyme pattern of hepatoxicity. In addition, the drug, at all experimental doses, significantly induced (p < 0.05) formation of micronucleated polychromatic erythrocytes in the bone marrow cells of the treated rats compared with the negative control indicating clastogenic potential of the drug when misused.

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.

Comparative effects of three naturally occurring furanocoumarins on mitochondrial bioenergetics

Oxygraphic measurements of the rates of mitochondrial respiration in the presence of varying amounts of chalepin, imperatorin and marmesin, three naturally occurring furanocoumarins, revealed that the oxidation of NAD(+)-linked substrates was inhibited by chalepin and imperatorin and less significantly by marmesin. The order of potency being rotenone much greater than chalepin imperatorin greater than marmesin. There was no effect whatsoever on succinate oxidation by the furanocoumarins tested (up to 60 microM). State 3 respiration was also inhibited by these furanocoumarins; by at least 80% by 10 microM chalepin and by 48 and 29% with 60 microM imperatorin and 60 microM marmesin, respectively. Consequently, ADP control of respiration was diminished by those concentrations of furanocoumarins that inhibited respiration. At 60 microM, respiratory control ratio was reduced by about 88, 49 and 28% with chalepin, imperatorin and marmesin, respectively. A measurement of the rate of proton and Ca2(+)-movements across the mitochondrial coupling membrane demonstrated that succinate-supported transport was not affected by these furanocoumarins. On the other hand, pyruvate/malate-supported proton ejection was significantly inhibited by chalepin, imperatorin and marmesin. The order of the degree of inhibition of proton flux is rotenone much greater than chalepin greater than imperatorin greater than marmesin. The pattern of the inhibition of pyruvate/malate-supported Ca2(+)-transport was identical to that seen during proton transport. A comparison of the effects of chalepin to that of rotenone suggests that chalepin might be about 10 times less potent than rotenone.

In vitro effects of aflatoxin B1 on the activities of three hydrolases.

The in vitro effects of aflatoxin B1 on the activities of trypsin, amylase and lipase in the pancreatic extract of male albino Wistar rats have been studied. Activities of the 3 hydrolases were inhibited at 1 microgram/ml, 200 microgram/ml and 400 microgram/ml concentrations of aflatoxin B1, with the exception that at the 1 microgram/ml concentration the activity of lipase was stimulated. Lineweaver-Burk reciprocal plots indicate non-competitive inhibition of the 3 hydrolases.

The effect of functional groups on the interaction of aflatoxins B1 and G1 with starch, cellulose and seven cellulose derivatives.

Abstract The interactions of starch, cellulose, phosphocellulose, diethyl amino cellulose (DEAE-C), trimethylamino ethyl cellulose (TEAE-C), cellulose-acetate, carboxymethyl cellulose (cm-c), cellulose Ecteola (Ecteola-c) with aflatoxins B1 and G1 were studied by equilibrium dialysis. The ligands bind with starch at two sites but with ECTEOLA-C, DEAE-C and TEAE-C at one site. No significant binding to other derivatives of cellulose was observed. The chemical groups: -CH2-CH2-N(CH2-CH3)2 (DEAE), -(CH2,-CH2-N+(CH2-CH3)3 (TEAE), and -CH2-CH2-CH2-N+CH2-CH2-OH)3 (ECTEOLA), seem to aid binding. They are, however, not critical prerequisites for binding to occur since there was binding to starch in which these chemical groups are absent.

Abstract A06: Electronic waste in Nigeria: potential for genotoxicity and metalloid induced carcinogenesis

Background: Used and discarded electronic items from developed countries often end up in developing countries. If still functional, they are traded as second-hand goods. But, with a diminished lifespan, they rapidly transit into unusable electronic waste (e-waste). The majority of these countries have no regulations for the disposal or recycling of e-waste. Consequently, the environmental hazard of e-waste is exacerbated by crude recycling methods: primarily as a source of livelihood, poor city dwellers scavenge and trade plastic and metal components from e-waste dump. The remainders are burnt in the open spewing toxic fumes into the atmosphere. Leachates from e-waste dumps percolate into the groundwater, may bio-accumulate on entering the food chain with potentials for toxic exposure. Globally, e-wastes pose a major public health-threat primarily to the populations of developing countries, their genomic integrity, and long-term health. Methods: Using Atomic Absorption Spectrometry (AAS) we determined the presence of Cadmium (Cd), Nickel (Ni), Chromium (Cr), Lead (Pb), Iron (Fe), Zinc (Zn) and Copper (Cu) in e-waste contaminated soil, e-waste ashes and water leachate from a dumpsite in Lagos, Nigeria, compared to soil sample 1000 meter away. We also assessed the effect of e-waste leachates on E. coli PQ-37 genomic integrity by the SOS inducing potency (SOSIP). E. coli PQ-37 was exposed to the samples and 4-Nitro-quinoline-oxide (4NQO) (positive control). Colorimetric changes were measured by spectrophotometry at 630nm (genotoxicity) and 450nm (viability). Results and Discussion: The detected heavy metals (ranges; Cd: 4 -18; Ni:12-26; Cr:4- 26; Pb:3-46; Fe:3489 – 8080; Zn:8-280; and Cu:1250–6700 μg/L) in test samples evaluated (p Citation Format: Solomon E. Owumi, Michael A. Gbadegesin, Ferdnand C. Osuagwu, Eberechukwu Onuchukwu, Bolaji Ayoola, Oyeronke A. Odunola, Anthony O. Uwaifo. Electronic waste in Nigeria: potential for genotoxicity and metalloid induced carcinogenesis. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A06.