Biliary lipid peroxidation products in gallbladder cancer: increased peroxidation or biliary stasis?

Abstract

Gallbladder cancer is a common malignancy among women in India. The aetiology of gallbladder carcinoma is still obscure and although numerous factors have been implicated, none has stood the test of time. This study was carried out to evaluate the role of lipid peroxidation product 4-hydroxynonenal (HNE) in gallbladder carcinogenesis. High-performance liquid chromatography (HPLC) analysis was carried out in 30 bile samples obtained during laparotomy from patients with gallbladder cancer (n = 10), cholelithiasis (n = 10) and age- and sex-matched controls (n = 10). A significantly high concentration of HNE and lower concentration of biliary pH and electrolyte was observed in patients with carcinoma of the gallbladder compared with controls and patients with cholelithiasis. A significant correlation was also observed between biliary Na+ and K+ (r = 0.72), biliary Ca2+ and Na+ (r = 0.69) among controls. However, there was no correlation between HNE, electrolytes and pH among cancer patients. An increased concentration of biliary HNE and decreased concentration of electrolytes suggest biliary stasis rather then increased peroxidation in cancer patients.

Cytochrome P‐450 expression and lipid peroxidation in gallbladder cancer

“…Earlier studies have proposed a probable role for cytochrome and free radical-mediated lipid peroxidation in gallbladder carcinogenesis [12][13][14]. The results of the present study show a significant increase in the concentration of both cytochrome P-450 and MDA in carcinoma of the gallbladder; however, the correlation studies failed to show any significant correlation between the two.…”

“…Cholelithiasis is considered, however, as the first and foremost risk factor [7,8], followed by chronic cholecystitis [8], chemical carcinogens [9,10], bile acids [4,11], lipid peroxidation products [12][13][14], biliary tract infection [11], typhoid carrier state [15,16], heavy metals [17], and blood groups [18].…”

“…Earlier we had proposed that increased lipid peroxidation in hepatocytes of patients with gallbladder cancer can lead to increased excretion of carcinogenic aldehydes into the gallbladder; if they remain in contact with the gallbladder mucosa for a longer time, these lipid peroxidation products may give rise to gallbladder carcinogenesis [12]. However, additional studies suggested that it is probably due to concentrating properties of gallbladder, rather than to overproduction [14]; it is also hypothesized that the lipid peroxidation within the gallbladder itself may contribute to increased concentration of lipid peroxidation products in gallbladder bile, coupled with stasis, this can give rise to gallbladder cancer. In the present study, our aim was to look at the presence of cytochrome P-450 in gallbladder mucosa and to correlate its expression with concentration of lipid peroxidation products.…”

Erythrocyte membrane fatty acid profile and saturation index in gallbladder carcinogenesis: a case-control study

“…Although not much delta 9 desaturation was seen in the present study when compared to the results of our earlier study [11], however this may be due to less number of patients in our earlier study and high variance thus observed. We had earlier proposed a role of free radical mediated lipid peroxidation in gallbladder carcinogenesis, however, our attention was subsequently drawn to the relationship of lipid peroxidation product 4-hydroxynonenal (HNE) and electrolytes suggesting that increase in lipid peroxidation products was probably due to increased stasis rather than increased peroxidation [12]. Even though the concentration of biliary lipid peroxides were not measured in the present study the fatty acid profile changes observed here probably indicate mechanism other than lipid peroxidation in gallbladder carcinogenesis.…”

Advanced gallbladder cancer: Indian “middle path”

“…Indian groups have also been studying alterations in bile composition in patients with GBC. [81][82][83][84][85][86][87] The AIIMS group has also investigated the role of the typhoid-carrier state in the causation of GBC. 88 The King George's Medical University, Lucknow group has evaluated the expression of p53 in GBC 89 and the GB Pant Hospital group has looked into the association between anomalous pancreatico-biliary ductal union and GBC.…”