Study on the role of Acetyl L Carnitine in mitigating the toxicity induced by 2 3 7 8 Tetrachlorodibenzo p dioxin in mice

Abstract

Therapeutic effect of ALC was first determined using HepG2 newlinecells by exposing to TCDD for 24h followed by treatment with ALC for an additional newline24h period. However, in preventive strategy, first the HepG2 cells were incubated newlinewith ALC for 24h and exposed to TCDD for additional 24h. In both conditions, the newlinelevels of NFkB, COX-2 and iNOS were measured using flow cytometry and newlinecompared with untreated control cells and the cells exposed to TCDD. In animal newlinestudies, mice (n=5) were administered with 100ng/kg body weight TCDD for 30 days, newlineand treated with ALC (Oral, 50mg and 100mg/kg body weight) for additional 30 days. newlineThe collected livers from control and experimental animals were fixed in formalin, newlineembedded in paraffin to prepare FFPE blocks. Sections of 4and#956;M thickness were cut newlineand used to (a) stain with H and E for morphological examination; or (b) processed newlinefor IHC to measure the levels of NFkB, COX-2 and iNOS. newlineRESULTS: ALC protected the HepG2 cells from undergoing apoptotic death due to newlineTCDD exposure by inhibiting inflammatory markers NFkB, COX-2 and iNOS as well newlineas by down regulating the expression of caspase-3. In animals, TCDD treated mice newlineshowed high hepatotoxicity as evidenced by increased lipid peroxidation, decreased newlineglutathione and superoxide dismutase, catalase and glutathione peroxidase levels. newlineOral administration of ALC protected against TCDD-induced hepatotoxicity by newlinesuppressing the expressions of TCDD induced inflammatory markers NFkB, iNOS, newlineand COX-2 as well as by promoting the levels of antioxidants. newlineSUMMARY: In conclusion, results of our study demonstrated the ability of ALC to newlineprotect against TCDD induced hepatotoxicity through the inhibition of inflammatory newlineproteins as well as by upregulating antioxidants in preclinical animal models newline newline