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Background and Aims: Increased susceptibility to gastric mucosal injury is observed in portal hypertensive gastropathy (PHG). In this study, the effects of zinc L-carnosine, an anti-ulcer drug, were evaluated on expression of heat shock protein (hsp) 72 and cytoprotection in gastric mucosa in a rat model of PHG. Methods: Portal hypertensive gastropathy with liver cirrhosis was induced by bile duct ligation for 4 weeks in male Sprague–Dawley rats. Expression of gastric mucosal hsp72 was evaluated by Western blotting at 6 h after intragastric administration of L-carnosine, zinc sulfate, or zinc L-carnosine. Blood was also collected for determination of serum zinc level. Mucosal protective abilities against hydrochloric acid (HCl) (0.6N) followed by pretreatment with L-carnosine, zinc sulfate or zinc L-carnosine were also studied. Results: L-carnosine, zinc sulfate, and zinc L-carnosine induced hsp72 in gastric mucosa of rats with bile duct ligation. Zinc sulfate and zinc L-carnosine suppressed HCl-induced mucosal injury. However, L-carnosine could not suppress HCl-induced mucosal injury. Serum zinc levels were significantly elevated after zinc L-carnosine administration. Furthermore, pretreatment with zinc L-carnosine (30–300 mg/kg) increased the expression of hsp72 in gastric mucosa and prevented HCl-induced mucosal injury in rats with bile duct ligation in a dose-dependent manner. Conclusions: Zinc derivatives, especially zinc L-carnosine, protected portal hypertensive gastric mucosa with increased hsp72 expression in cirrhotic rats. It is postulated that zinc L-carnosine may be beneficial to the mucosal protection in PHG as a ‘chaperon inducer’. [ABSTRACT FROM AUTHOR]

Abstract: During the course of liver cirrhosis, severe renal complications frequently occur. However, the pathogenesis of renal dysfunction in liver cirrhosis has not been completely understood. In this study, we investigated the association between renal function and expressions of renal heat shock proteins (HSPs) in biliary cirrhotic rats. Following bile duct ligation (BDL), renal function and expressions of HSPs were compared in control and BDL cirrhotic rats. Serum BUN and creatinine levels were significantly higher in cirrhotic rats compared with control rats at 4 weeks post-BDL operation. Renal expressions of HSP72 and HSP25 were decreased with progression of liver cirrhosis in BDL rats by Western blotting. Immunohistochemistry revealed that expression of renal HSP72 was suppressed in tubular epithelial cells, and expression of renal HSP25 was suppressed not only in tubular epithelial cells but also in blood vessels in rats with liver cirrhosis. Renal expressions of HSP90 and HSP60 did not differ between control and BDL rats. Renal function was impaired in biliary cirrhotic rats with decreased expressions of renal HSP72 and HSP25. These findings suggest that decreased expressions of renal HSP72 and HSP25 may be a part of the pathogenesis of renal dysfunction in liver cirrhosis. [Copyright &y& Elsevier]