Overexpression of cerebral cytochrome P450s in prenatally exposed offspring modify the toxicity of lindane in rechallenged offspring
Authors: Ankita Srivastava
Anshuman Singh
Devendra Parmar
Rakesh R Jha
Devendra K Patel
Sanjay Yadav
Anita Agrahari
Vikas Srivastava
Journal: Toxicology and Applied Pharmacology (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Brain; CYPs; Epigenetic; Lindane; Metabolism
Affiliations: Developmental Toxicology Laboratory, System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (IITR), Vishvigyan Bhavan, 31, M.G. Marg, Lucknow 226 001, UP, India; Department of Biochemistry, College of Dental Sciences, Babu Banarasi Das University, Lucknow 226028, UP, India., Developmental Toxicology Laboratory, System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (IITR), Vishvigyan Bhavan, 31, M.G. Marg, Lucknow 226 001, UP, India., Developmental Toxicology Laboratory, System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (IITR), Vishvigyan Bhavan, 31, M.G. Marg, Lucknow 226 001, UP, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, UP, India., Regulatory Toxicology Group, CSIR-IITR, Lucknow 226 001, UP, India., Developmental Toxicology Laboratory, System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (IITR), Vishvigyan Bhavan, 31, M.G. Marg, Lucknow 226 001, UP, India. Electronic address: .

Abstract:  Prenatal exposure to low doses of lindane, an organochlorine insecticide used in public health and agriculture, induced a persistent increase in the expression of cerebral cytochrome P450s (CYPs) in rat offspring and modify the adult response to a later exposure of xenobiotics. To understand the mechanism involved in the modification of adult response, rat offspring exposed prenatally to lindane (p.o.; 0.25 mg/kg b.wt. from gestation day 5-21) were rechallenged with lindane (p.o.; 5 mg/kg X 5 days) postnatally at 9- or 18- or 27 weeks. The greater magnitude of increase in the expression of cerebral CYPs in rechallenged offspring and decline in the magnitude of increase in CYPs with increasing age correlated with the amount of lindane accumulating in the brain. Significant alterations in the circulatory levels of hormones in the rechallenged offspring suggest that these alterations may partly account for the persistence in the increase in the cerebral CYPs during development. Epigenetic data further revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of cerebral CYPs isolated from rechallenged offspring at 9- or 18- or 27 weeks. Bisulphite sequencing revealing critical CpG methylation changes in the promoter regions in rechallenged offspring at 9 weeks demonstrated imprinting of the cerebral CYPs. Further, a greater magnitude of increase in apoptosis in the brain of rechallenged offspring has suggested that enhanced responsiveness of cerebral CYPs, which may result due to alterations in circulatory hormones, increased accumulation of lindane in the brain and epigenetic regulation of CYPs, is of toxicological relevance. 

Retracted: No

PubPeer comments:
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 I agree these are very similar, although maybe not the *same.* Perhaps the authors can provide additional images to clarify. Below Iu2019ve layered the images to illustrate similarity. *** ![file] , 
 #3 Perhaps I was not clear in my reply. I agree with you that they show unexpected similarity and the authors should address that. My eyes do see very slight differences that, even if accurate, do not diminish the seriousness of your concern. , 
 Taking the negative of one version, and superimposing it on the other so that identical pixels cancel out, certainly fosters the impression that there are few differences between the two Actin blots. ![file] , 
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 #1 Figure 8. Bands lanes 1 and 2 of 18 week caspase 3 panel appear to be very similar. Band lane 2 of 27 week bax panel appears to more similar mirror image of band lane 1 of 27 week Bax panel than you woud expect. , 
 #2 Dear Actinopolyspora Biskrensis, could you show any difference between both blots. Why you used the word  perhaps . Both blots are copy and paste images of each other without any doubt. , 
 Beta actin blots from same tissue samples could appear remarkably similar when processed, run and probed at the same time. The first hand experimenter could vouch for it. , 
 #Biomphalaria Cousini Only first hand experimenter could give this type of statement. Everybody know that b actin from samples of different age groups never be exactly similar even all the experimental conditions were same. Because there is always a significant difference that can be easily differentiated by naked eyes due to variation of amount of protein transfer from gel to membrane and the arrangement of blot in developer machine during exposure. ,