Adebayo Lawrence Adedeji

Impaired lipid levels and inflammatory response in rats exposed to cadmium

To investigate the subchronic effect of cadmium intoxication on lipid metabolism and the inflammatory responses accompanying it, rats were administered 50 and 100 ppm cadmium through their drinking water for 7 weeks. At both concentrations, cadmium exposure resulted in significant elevation (p < 0.05) of total cholesterol and gave rise to hypertriglyceridemia in the plasma of the animals. The proinflammatory cytokines, IL-2, IL-6 and TNF-α, were highly expressed in the animals. At the 50 ppm dose level, plasma IL-2, IL-6 and TNF-α levels were increased by 20 %, 87 % and 336 % respectively, while the 100 ppm dose yielded 32 %, 57 % and 470 % increases, respectively. A drastic build-up of MDA in the liver elicited by the metal led to an 85 % increase in lipid peroxidation at high dose. A 3-fold increase of lipid hydroperoxidation (LOOH) products was obtained on exposure to cadmium at 100 ppm. Cadmium caused more than a 2-fold increase in oxLDL levels at both doses tested. Paraoxonase activity was also significantly repressed, culminating in a 43 % reduction in activity at 100 ppm dose. Disruption of lipid metabolism, increased lipid peroxidation as well as imbalance in proinflammatory cytokine levels may thus, be means by which cadmium induces its toxicity.

Oxidative indices correlate with dyslipidemia and pro-inflammatory cytokine levels in fluoride-exposed rats.

Abstract The aim of this study was to establish the effects of fluoride on lipid metabolism and attendant inflammatory response by exposing rats to 50 mg L-1 and 100 mg L-1 of fluoride through drinking water for seven weeks. Both concentrations led to hypercholesterolemia while the 100 mg L-1 concentration induced hypertriglyceridaemia. High density lipoprotein (HDL) cholesterol levels dropped in the exposed rats while interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05). Fluoride-exposed rats also had significantly higher levels of liver malondialdehyde (MDA) and plasma lipid hydroperoxide (LOOH) but lower plasma paraoxonase (PON1) activity. Oxidative stress indices correlated with pro-inflammatory cytokines and plasma cholesterol. In contrast, proinflammatory cytokines inversely correlated with plasma triglyceride, HDL cholesterol and PON1. Our results suggest that the association between fluoride exposure with cardiovascular diseases may be related to its ability to disturb lipid homeostasis, and trigger pro-inflammatory cytokines and oxidative stress. Sažetak Svrha je ovog istraživanja bila utvrditi djelovanje fluorida na metabolizam lipida i upalni odgovor tako što smo štakore izložili fluoridu u pitkoj vodi u koncentracijama od 50 mg L-1 i 100 mg L-1 sedam tjedana. Obje su koncentracije dovele do hiperkolesterolemije, a viša je koncentracija inducirala i hipertrigliceridemiju. U odnosu na kontrolnu skupinu, u izloženih su se štakora razine lipoproteina visoke gustoće (HDL-a) smanjile, a interleukin 2 (IL-2) se povećao više od 1,5 put (p<0,05), kao i IL-6 i čimbenik tumorske nekroze alfa (TNF-α) u plazmi, i to više od 2,5 puta (p<0,05). Usto su izloženi štakori iskazali značajno više razine malondialdehida (MDA) u jetrima te lipidnog hidroperoksida (LOOH) u plazmi, odnosno sniženu aktivnost paraoksonaze (PON1) u plazmi. Indikatori oksidacijskog stresa korelirali su s upalnim citokinima i kolesterolom u plazmi, a upalni citokini inverzno su korelirali s trigliceridima, HDL kolesterolom i PON1 u plazmi. Rezultati istraživanja upućuju na to da povezanost između izloženosti fluoridu i bolesti srca i krvožilja možda potječe od toga što fluorid remeti lipidnu homeostazu te pokreće upalne citokine i, posljedično, oksidacijski stres.

Abstract 3792: Upregulation of TNF-α by ethanol extract of Moringa oleifera leaves in benzene-induced leukemic Wister rat: a possible mechanism of anticancer property

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Ethanol extract of Monringa oleifera leaves has been shown to possess anticancer properties in animal models. The mechanisms of action of its anticancer properties have not been fully demonstrated. In this study, we induced leukemia in two groups of 7 rats each by intravenous injection of benzene chromasolv solution (0.2 mL) 48 hourly for 4 weeks. The extract (0.2 ml of 100 mg/mL) was administered orally by gavage, after leukemia induction, daily for 4 weeks to one of the groups while the other group was not treated. The third group served as the normal control. At the end of the treatment, the rats were immobilized by cervical dislocation and blood samples were collected by cardiac puncture. Plasma concentrations of Beta-2 Microglobulins (β2M), Perforins (PF), Interleukin-2(IL2), Interferon-gamma (IFN-γ) and Tumour Necrosis Factor-alpha (TNF-α) were determined by standard commercial ELISA Results showed that leukemia was induced within 4 weeks as a significantly elevated leukocyte count and plasma β2M concentration over the baseline were noted (p< 0.05). Plasma IL2 and TNF-α were also significantly elevated while PF and IFN-γ decreased significantly in Moringa oleifera leaves extract treated rats compared with untreated groups. Since IL2 and PF are associated with cytotoxicity of CD8 T lymphocytes, reduced expression of PF in the face of increasing plasma concentration of IL-2 suggests that Moringa oleifera extract may not exert its anticancer properties via direct cytotoxicity. We thus concluded that increased expression TNF-α may translate to enhanced apoptosis and may be a possible mechanism of action. Citation Format: Olufemi E. Akanni, Adebayo L. Adedeji, Kola J. Oloke. Upregulation of TNF-α by ethanol extract of Moringa oleifera leaves in benzene-induced leukemic Wister rat: a possible mechanism of anticancer property. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3792. doi:10.1158/1538-7445.AM2014-3792

CD57 expression by T cells in the female genital tract of HIV-zx1 infected women

Despite an influx of T cells to the cervix during HIV infection, genital T cells are not associated with control of HIV shedding. CD57 expression by T cells has been associated with enhanced migratory potential and CD57+ T cells have been shown to accumulate in tissues during the late stages of HIV disease. We investigated the impact of HIV-infection and clinical status on the expression of CD57 by T cells from the female genital tract in 13 HIV-infected and 5 uninfected women. We found that cervical and blood-derived T cells expressed similar frequencies of CD57. The frequency of CD57 expression by cervical or blood T cells was not associated with clinical status (CD4 counts). No impairment in IFN-γ production by CD57+ T cells from the genital tract was observed. We conclude that increased T cell senescence does not appear to be a hallmark of genital mucosal HIV-1 infection.

Serum protein electrophoresis under effective control of HIV-1 disease progression

In this report, we compared the serum protein electrophoresis (SPE) patterns in a subset of HIV-1-infected subjects who did not progress to AIDS without antiretroviral treatment with those in whose control of disease progression was achieved by highly active antiretroviral therapy (HAART). SPE and immunofixation electrophoresis were performed on Helena Electrophoresis System according to manufacturer’s instructions. The percentage of SPE abnormalities, resembling chronic inflammation, was significantly higher in HIV-1-infected subject without HAART compared with those under HAART (p = 0.001). The majority of individuals under HAART showed evidence of oligoclonal bands on the γ-band against a polyclonal background compared with those without HAART but ß-γ-band bridging was more evident. Immunofixation pattern was consistent with oligoclonal hypergammaglobulinaemia of IgG kappa type, which was found to be more intense in group without HAART. HIV clinical status did not show appreciable effect on the SPE pattern in subjects without HAART. However, under effective HAART, subjects with better CD4 T-cell count were associated with higher γ-globulin band. In group without HAART, acute infection was found to be associated the higher γ-globulin fraction compared with chronic infection. The opposite was the case under effective HAART. HIV infected subjects that did not progress to AIDS were associated with markedly abnormal SPE pattern. Overall results reflect the host ability compensate defective cellular immunity in HIV-1 infection with humoral immune responses. These findings underscore the usefulness of SPE monitoring HIV disease management and identifying individuals that may not progress to full-blown AIDS in the absence of treatment.