Written by Chrystal Moulton, Staff Writer. Riboflavin was found to be associated with a higher survival rate in zebrafish exposed to lethal doses of cyanide.
In this particular study, researchers wanted to confirm that zebrafish could be used as a model for understanding how cyanide affects glucose metabolism, mitochondrion function, system failures and as well discover biological markers that could serve as signals for cyanide poisoning. They also wanted to determine through this model possible treatments for cyanide poisoning.
Zebrafish larvae were cultivated and tests were conducted to determine the effect of sub lethal levels of cyanide on heart rate, glucose levels, startle and light response. Researchers also performed chemical and metabolite screening to determine a reliable biological signal of cyanide poisoning.
Heart rate was measured after 2 hours of cyanide exposure. Researchers observed a gradual and significant decrease in heart rate in doses for 25 -400 micromoles of cyanide. They also observed a 50% reduction in heart rate at 100 micromoles of cyanide.
In order to evaluate the effect on glucose metabolism, larvae were exposed to 1 micromole cyanide for 8 hours. Researchers observed a decrease in glucose concentration, which indicates a switch from aerobic respiration to anaerobic respiration.
To measure neurological effects of cyanide, larvae exposed to cyanide were tested for their response to light. They found that larvae exposed to 30 mins of cyanide reacted slower to light stimulus. They also found that doses greater than or equal to 100micromoles of cyanide significantly caused basal activity to decrease, reaction time before motion to increase, and response to light stimulus to be suppressed.
All of these observations show zebrafish display very similar clinical effects to cyanide poisoning as humans and would likely serve as a good model for understanding and creating an antidote for cyanide poisoning.
In order to test for this possible antidote, zebrafish larvae were individually exposed to a lethal dose of cyanide (50 micromoles) along with 1 of 3,120 other molecules to see which could reverse or slow the progression of cyanide poisoning. Researchers found 4 possible treatments for cyanide poisoning: cisplatin, carboplatin, methotrexate, and riboflavin. Among them, riboflavin, when compared to current treatments for cyanide poisoning, was slightly more effective and demonstrated a 90% survival rate for zebrafish larvae when used with known cyanide scavengers.
Researchers also wanted to see whether riboflavin would be effective in reversing the neurological and metabolic effects of cyanide poisoning. In order to do this, they tested for biological markers of cyanide poisoning. Their tests revealed that sub lethal doses of cyanide caused significant increases in the concentration of bile acids and inosine. They then supplied riboflavin to larvae affected by the sub lethal dose of cyanide and found that riboflavin normalized bile acid and inosine concentrations and reversed deadly anaerobic cellular respiration back to aerobic respiration. This last test accomplished two things. It demonstrated the effectiveness and potential use of riboflavin in the treatment of cyanide poisoning. Furthermore, It also revealed a new indicator of cyanide poisoning: bile acids and inosine concentration.
So, in order to further verify these new indicators of cyanide poisoning, researchers tested the metabolic effects of sublethal doses of cyanide in rabbits and compared these results with humans exposed to cyanide through nitroprusside, a drug normally given to individuals with advanced heart failure. They found that in both humans and rabbits exposed to cyanide bile acid and inosine concentrations increased significantly. According to this study, riboflavin could be used as a possible treatment of cyanide poisoning and both bile acids and inosine may serve as useful markers for cyanide toxicity.
Source: Nath, Anjali K., et al. “Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure.” The FASEB Journal 27.5 (2013): 1928-1938.
© 2017 by the Federation of American Societies for Experimental Biology
Posted May 14, 2013.
Reference:
- Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. NathAK, Roberts LD, Liu Y, et al. FASEB J. 2013 May;27(5):1928-38. doi: 10.1096/fj.12-225037. Epub 2013 Jan 23.
