Mislabeled chemical bottle leads to retraction of liver protection paper

A labeled chemical bottle may contain a genie and not the expected reagent, according to a cautionary retraction that could be a warning for all bench researchers.

Sreenivasan Sasidharan, a researcher at the Institute for Research in Molecular Medicine (INFORMM), part of the Universiti Sains Malaysia, used a bottle labeled lantadene A, a liver-destroying chemical from the leaves of the Lantana camara plant that some livestock eat.

Sasidharan found that contrary to expectations, “lantadene A” protected livers against damage from acetaminophen — aka Tylenol.

But Manu Sharma, assistant pharmacy professor at Jaypee University of Information Technology in India, suspected something was technically amiss:

This claim that the authors were able to dissolve the non-polar pentacyclic triterpenoid lantadene A in water was quite surprising to me, as the Toxnet database reports the calculated solubility of lantadene A in water at 25 °C as just 7.68 × 10−5 mg/L [2], suggesting that lantadene A is essentially insoluble in water. The facile solubilization of lantadene A in water mentioned in this paper thus raises questions about the identity of the compound actually tested and therefore the whole study and its conclusions.

An anonymous reader shared Sharma’s concerns. Turns out that the “lantadene A” in the bottle, ordered from Chemtron in Malaysia, wasn’t the expected chemical and remains a mystery — in an echo of a retraction we covered two years ago in which a bottle labeled rhodium was actually full of palladium.

The retraction reads in full:

A recent Comment by M. Sharma published in the journal Molecules [1] raises issues with our previously published paper [2]. After reviewing its content, and although we respectfully stand by our experimental description whereby we were able to prepare stock and working solutions of the substance being tested, the arguments presented do raise concerns about the true identity of the compound actually used and hence the results and conclusions of our paper.

Unfortunately, since becoming aware of this, we have been unable to characterize the original sample, now used up, and we have been unable to obtain a verified equivalent one from the local commercial supplier we used. In light of these facts, since we can no longer associate with any confidence our experimental results with the compound lantadene A, we would like to withdraw our paper until such a time that we can obtain a new sample, check its identity and redo the work. As to the comments regarding erroneous citation of references, we feel that since the paper is to be removed from the scientific record, any additional corrections are unnecessary at this time. As corresponding author I take full responsibility for the omission of not checking the compound used in our experiments and any errors in its contents, and would like to offer my apologies on behalf of my co-authors to the readership of Molecules for any inconveniences caused by this omission

References

1. Sharma, M. Remarks on Sasidharan et al. “Evaluation of the Hepatoprotective Effects of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants Against Acetaminophen-induced Liver Damage”. Molecules 2012, 17, 13937–13947. Molecules 2013, 18, 3442–3444.

2. Grace-Lynn, C.; Chen, Y.; Latha, L.Y.; Kanwar, J.R.; Jothy, S.L.; Vijayarathna, S.; Sasidharan, S. Evaluation of the Hepatoprotective Effects of Lantadene A, a Pentacyclic Triterpenoid of Lantana Plants against Acetaminophen-induced Liver Damage. Molecules 2012, 17, 13937–13947.

Here are those “comments regarding erroneous citation of references” from Sharma that the authors didn’t feel the need to address:

Finally, there are a number of other statements made in the paper that cite references in error. For example, the authors wrote in last line of the Introduction: “Thus the current study was conducted to investigate how lantadene A is associated with hepatoprotection or hepatotoxicity as this compound is used in the development of drugs”, yet the reference cited to support this statement (reference number [1] in the paper) contains no such information supportive of this fact. Moreover, reference [23] in the paper, cited by the authors to explain the protocol for induction of hepatotoxicity by acetaminophen does not contain anything related to hepatotoxicity, as the topic of said reference is the characterization of the SOS regulon of Caulobacter crescentus, so it’s surprising to this author that Sasidharan et al. would have used this reference in relation to the hepatotoxicity induction protocol. Such carelessness in any research paper published in a peer reviewed journal is not acceptable.

We contacted the editor-in-chief of Molecules, Derek J. McPhee, and he illuminated the already thorough retraction:

Prof. Sasidharan was given time (several months in fact) to check the identity of the compound they had tested. But as stated in the retraction, they had used up all the original sample and were unable to procure a verifiable replacement sample from the small local chemicals supplier they had used. We do not publish “amendments”…but in this case without the identity of the compound tested, the biological data is essentially useless, hence the decision to retract the paper.

The “standing behind the data” statement in no way implies the compound is correct – what it means that the authors were able to prepare aqueous solutions of some compound they had purchased from a commercial supplier under the assumption it was lantadene A (but which almost certainly was not lantadene A) and they are confident that the biological activity measured for those solutions is correct, even though without the true identity of the compound this data it is of little use to the scientific community, hence the retraction.

The moral of the story is to not blindly trust labels on commercial chemical bottles or even better, to always apply the (former U.S. president Ronald) Reagan approach: ‘trust, but verify’.

We reached out to Sasidharan, and will let you know if he gets back to us.