Olusegun Kayode Afolabi

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.