Ameliorative effect of curcumin and vitamin B6 against lithocholic acid-induced cholestasis and liver injury in mice

To examine the therapeutic effect of curcumin and/or vitamin B6 in treatment of cholestasis, a model of cholestasis was induced in mice using lithocholic acid (LCA). Alterations in biochemical parameters and liver histopathological and histochemical changes were examined in cholestatic mice and after treatments with curcumin, vitamin B6 and combination of both. Moreover, hepatic expressions of bilirubin-metabolizing enzymes, their regulatory nuclear receptors, and bile acid lipid transporters were examined using RT-PCR. Cholestatic mice showed an increase in the blood levels of AST, ALT, ALP, direct and total bilirubin and a decrease in cholesterol levels that were ameliorated by treatments. Liver histopathology showed multiple necrotic foci of different sizes spread all over the liver with congestion of hepatic blood vessels in LCA group. These foci were regenerated in hepatic tissues after administration of curcumin and vitamin B6. Immunohistochemical examination of liver showed an increase in glutathione and NF-kB expressions in treated mice. Cholestatic mice showed down-regulation of mRNA expression of hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Oatp2, Bsep, Mrp2, Abcg8, Asbt). These changes were ameliorated and restored by treatment with curcumin, vitamin B6 and both. Only of examined genes, NTCP was up-regulated in cholestatic mice. In conclusion, treatment with curcumin mainly, vitamin B6 or the combination of them has the potential to ameliorate changes observed in induced cholestasis.

Ameliorative effect of curcumin and vitamin B6 against lithocholic acid-induced cholestasis and liver injury in mice

To examine the therapeutic effect of curcumin and/or vitamin B6 in treatment of cholestasis, a model of cholestasis was induced in mice using lithocholic acid (LCA). Alterations in biochemical parameters and liver histopathological and histochemical changes were examined in cholestatic mice and after treatments with curcumin, vitamin B6 and combination of both. Moreover, hepatic expressions of bilirubin-metabolizing enzymes, their regulatory nuclear receptors, and bile acid lipid transporters were examined using RT-PCR. Cholestatic mice showed an increase in the blood levels of AST, ALT, ALP, direct and total bilirubin and a decrease in cholesterol levels that were ameliorated by treatments. Liver histopathology showed multiple necrotic foci of different sizes spread all over the liver with congestion of hepatic blood vessels in LCA group. These foci were regenerated in hepatic tissues after administration of curcumin and vitamin B6. Immunohistochemical examination of liver showed an increase in glutathione and NF-kB expressions in treated mice. Cholestatic mice showed down-regulation of mRNA expression of hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Oatp2, Bsep, Mrp2, Abcg8, Asbt). These changes were ameliorated and restored by treatment with curcumin, vitamin B6 and both. Only of examined genes, NTCP was up-regulated in cholestatic mice. In conclusion, treatment with curcumin mainly, vitamin B6 or the combination of them has the potential to ameliorate changes observed in induced cholestasis.(AU)

Secondary bile acids effects in colon pathology. Experimental mice study

To assess whether deoxycholic acid (DOC) and lithocholic acid (LCA) administered in a period of six months in a concentration of 0.25% may have a carcinogenic role in mice colon. The study used C57BL6 female mice divided into four groups. The control group received a balanced diet and the others received diets supplemented with 0.25% DOC, 0.25% LCA and 0.125% DOC+0.125% LCA, respectively. After euthanasia, the lesions found in the resected gastrointestinal tracts were stained with hematoxylin-eosin and examined microscopically. No gastrointestinal tract changes were observed in the control group, while hyperplastic Peyer's patches in the small intestine, flat adenomas with mild dysplasia and chronic colitis at the level of the colon were found in all three test groups. The colonic lesions prevailed in the proximal colon. The highest number of flat adenoma lesions (8), hyperplasia of Peyer's patches (25) and chronic colitis (2) were found in mice fed with diet and LCA. Precancerous or cancerous pathological lesions could not be identified. Instead, adenomatous colonic injuries occurred in a shorter period of time (six months), compared to the reported data.(AU)