| Abstract: | I.Potential effect of sodium nitrite on the expression of nuclear proto-oncogenes during 2-acetylaminofluorene-induced
hepatocarcinogenesis in rats 2-acetylaminofluorene(AAF) reacts in acidic conditions with nitrous fume yiel-ding N-nitrso-AAF (N-NO-AAF),as previously described,that exerts more toxic and mutagenic effects than its parental compound. In this study, the effect of sodiumnitrite (NaNO2) on the tumorgenicity of AAF in rats fed with AAF and NaNO2 was observed. Wistar rats were divided into five groups: group I served as control;group II treated with NaNO2(0.3%); group III was given 0.02% AAF alone; group IVand group V received both AAF and NaNO2 (0.2% and 0.3%
respectively) in diet for12 weeks. At the end of experimental, all rats in group III,IV and V developed early stage phenomena of hepatocellular carcinoma.including hepatomegaly with variable-size foci and neoplastic nodules. Severe damages were observed in the rats treated with AAF and NaNO2. Feeding with AAF(0.02%) for 3 months elevated the le-vels of c-Jun,c-Fos and c-Myc proteins in the rats livers. The AAF-induced c-Jun,c-Fos and c-Myc expressions were significantly magnified (p<0.001) by NaNO2. These data confirmed that the strengthening of AAF- induced hepatocarcinogenesis by NaNO2 should be associated with its enhancing effect on the AAF-induced incre-ases in the
expressions of c-Jun,c-Fos and c-Myc. II.Inhibition by Hibiscus protocatechuic acid of Lipopolysaccharide-induced endo-genous Nitric oxide production and NO-AAF formation in rats Nitrosocompound ,which can cause cancer by directly attacking DNA to form DNAadducts,can be produced in vivo,indicating that endogenous nitric oxide (NO) plays an important role. NO,either exogenous or endogenous,can nitrosate secondary amines,thus causing cancer. Endogenous NO would response to infection via inducible NOsynthase which could be activated by various microorganisms. Inducible NO synthasealso exists in hepatocyte and is activated by cytokines from Kupffer cells in infe-ction.
Therefore,it was hypothesized that reduced endogenous NO in infection may contribute to prevention in chemical
carcinogenesis caused by nitroso compounds.Hibiscus protocatechuic acid (PCA),an antioxidant,can scavenge oxygen
free radicals with the catechol structure. It was hypothesized if PCA could inhibit the elevationof endogenous NO induced by Lipopolysaccharide (LPS),via scavenging free radicals,it would prevent nitrosation reaction progression. Significantly
reduced endogenous NO production was demonstrated in rats treated with PCA. In addition,rats pretreated with PCA inhibited slightly hepatitis caused by AAF, Thus,PCA can be used as an efficient chemopreventor in carcinogenesis caus-ed by nitrosation of endogenous NO via free radical scavenging action. Endogenous NO production,induced by Lipopolysaccharide,in physiological condi-tions,reacts with target molecules (Heme proteins,Fe-S proteins,SH groups,Other non-heme Fe and metalloproteins,Amines,DNA,Oxygen,Superoxide anion, Hydrogen peroxide),so that NO reacted with AAF may be difficult to detect. Detect N-NO-AAF by Spectrophotometer method and by
HPLC method showed not detect-able. Rats treated with LPS and AAF showed variable necrosis: in group III(LPS only) showed focal necrosis;in group V (LPS and AAF) showed severe liquefactive necrosis;in group VII (PCA 50mg/Kg.andLPS and AAF), in group VIII (PCA 100mg/Kg.and LPS andAAF), in group IX (PCA 250mg/Kg. and LPS and AAF) showed liquefactive necrosis in these groups. |
