Acute renal failure and hepatitis following ingestion of carp gallbladder.

INTRODUCTION: Fish gallbladder has long been used as folk remedy in China. Poisoning due to carp gallbladder ingestion has been reported in many countries but the majority of cases are in Chinese journals. We report a case of grass carp gallbladder poisoning and review the literature, including the Chinese reports. CASE REPORT: A 67 year old woman ingested a grass carp gallbladder and complained of nausea and epigastric pain in two hours, and had elevated alanine aminotransferase by 8 hours. She developed oliguria on day three and hemodialysis was performed on day five, following which she gradually recovered and was discharged on day 26. DISCUSSION: Carp gallbladder contains 5 alpha-cyprinol sulphate, which is hepatotoxic and nephrotoxic. The exact mechanism of toxicity is unknown. Mild poisoning causes only gastroenteritis, liver and kidneys are affected in moderate poisoning, and multi-organ failure occurs in severe poisoning. The initial symptoms are nausea, vomiting, diarrhea and abdominal pain, which usually occur 5 to 12 hours after ingestion. Raised liver enzymes or jaundice occurs in 75% to 87% of patients. Acute renal impairment occurs in 72% to 87% of patients, usually on day 3 to 6. Treatment is supportive and often included hemodialysis. CONCLUSION: The ingestion of grass carp gallbladder may result in transient hepatitis with subsequent acute renal failure. This case also illustrated the importance of understanding the use and potential serious complications of alternative medicines. Fish gallbladder poisoning should be considered in unexplained acute renal failure in Chinese and Asian patients.

Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the absence of functional Mdr2, Abcg5, and Abcg8 transporters.

The ABC transporters bile salt export pump (BSEP; encoded by the ABCB11 gene), MDR3 P-glycoprotein (ABCB4), and sterolin 1 and 2 (ABCG5 and ABCG8) are crucial for the excretion of bile salt, phospholipid, and cholesterol, respectively, into the bile of mammals. The current paradigm is that phospholipid excretion mainly serves to protect membranes of the biliary tree against bile salt micelles. Bile salt composition and cytotoxicity, however, differ greatly between species. We investigated whether biliary phospholipid and cholesterol excretion occurs in a primitive species, the little skate, which almost exclusively excretes the sulphated bile alcohol scymnolsulphate. We observed no phospholipid and very little cholesterol excretion into bile of these animals. Conversely, when scymnolsulphate was added to the perfusate of isolated mouse liver perfusions, it was very well capable of driving biliary phospholipid and cholesterol excretion. Furthermore, in an erythrocyte cytolysis assay, scymnolsulphate was found to be at least as cytotoxic as taurocholate. These results demonstrate that the little skate does not have a system for the excretion of phospholipid and cholesterol and that both the MDR3 and the two half-transporter genes, ABCG5 and ABCG8, have evolved relatively late in evolution to mediate biliary lipid excretion. Little skate plasma membranes may be protected against bile salt micelles mainly by their high sphingomyelin content.

Squalamine, a novel cationic steroid, specifically inhibits the brush-border Na+/H+ exchanger isoform NHE3.

Squalamine, an endogenous molecule found in the liver and other tissues of Squalus acanthias, has antibiotic properties and causes changes in endothelial cell shape. The latter suggested that its potential targets might include transport proteins that control cell volume or cell shape. The effect of purified squalamine was examined on cloned Na+/H+ exchanger isoforms NHE1, NHE2, and NHE3 stably transfected in PS120 fibroblasts. Squalamine (1-h pretreatment) decreased the maximal velocity of rabbit NHE3 in a concentration-dependent manner (13, 47, and 57% inhibition with 3, 5, and 7 micrograms/ml, respectively) and also increased K'[H+]i. Squalamine did not affect rabbit NHE1 or NHE2 function. The inhibitory effect of squalamine was 1) time dependent, with no effect of immediate addition and maximum effect with 1 h of exposure, and 2) fully reversible. Squalamine pretreatment of the ileum for 60 min inhibited brush-border membrane vesicle Na+/H+ activity by 51%. Further investigation into the mechanism of squalamine's effects showed that squalamine required the COOH-terminal 76 amino acids of NHE3. Squalamine had no cytotoxic effect at the concentrations studied, as indicated by monitoring lactate dehydrogenase release. These results indicate that squalamine 1) is a specific inhibitor of the brush-border NHE isoform NHE3 and not NHE1 or NHE2, 2) acts in a nontoxic and fully reversible manner, and 3) has a delayed effect, indicating that it may influence brush-border Na+/H+ exchanger function indirectly, through an intracellular signaling pathway or by acting as an intracellular modulator.