Indian Journal of Pharmacology Medknow Publications on behalf of Indian Pharmacological Society ISSN: 0253-7613 EISSN: 1998-3751 Vol. 41, Num. 5, 2009, pp. 243-243

Indian Journal of Pharmacology, Vol. 41, No. 5, September-October, 2009, pp. 243

Letter to the Editor

Authors' reply

Kavitha S Nair, Kirti V Patel, Tejal R Gandhi

Department of Pharmacology, Anand Pharmacy College, Opp Town Hall, Anand - 388 001, Gujarat, India

Correspondence Address:Kavitha S Nair, Department of Pharmacology, Anand Pharmacy College, Opp Town Hall, Anand - 388 001, Gujarat, India, kavitha21_82@yahoo.co.in

Code Number: ph09068

PMID: 20177499

Sir,

This is with reference to the comments on our paper as described above. ^[1] Few questions have been posed and the answers to the same are as follows:

1. It is true that NADPH is a cofactor for aldose reductase. The electrons are, however, supplied from NADPH via cytochrome P450 reductase, which is closely associated with cytochrome P450 in the lipid membrane of the smooth endoplasmic reticulum. ^[2] Thus, any reaction that will alter the synthesis of NADPH will be able to affect the aldose reductase pathway. However, in the current context, the synthesis of NADPH is not targeted as hypothesis, whereas the electron transfer from NADPH has to be targeted through cytochrome P450 modulation (i.e. either inhibition or induction).
2. It should be noticed that cytochrome P450 is present at various sites in the body, one of which is lens where the presence of the aldose reductase pathway is not debatable. Using phenobarbital, the occurrence of cataract through cytochrome P450 modulation has been amply demonstrated.
3. The cytochrome P450 induction will in no way affect the concentrations of NADPH but will increase the rate of reaction catalyzed by aldose reductase through supporting the electron transfer from NADPH. This forms the basis of hypothesis, whereby induction of cytochrome P450 is proposed to increase the occurrence of cataract and vice versa.
4. Even a minor amount of unbound drug could have a significant role to play. Moreover, the scope of an activity cannot be limited to just one factor alone.
5. It appears that the cytochrome modulatory role of pioglitazone is doubtful. However, an ample evidence has accumulated to support its role as a cytochrome P450 enzyme inducer (although weak).^[3],[4]
6. Galactose has not been used for induction of diabetes but for the induction of cataract. This is attributed to accumulation of galactitol in the lens. Rats fed with excess galactose accumulate galactitol within the lens. This results in an osmotic effect bringing in water and causing swelling and opacification. The key enzyme for this chain of action in lens is aldose reductase (AR).

References

1.	Mahajan R, Gupta K. Cytochrome modulation decreases the risk of cataract: Is thebasic hypothesis flawless? Indian J Pharmacol 2009;41:242.  Back to cited text no. 1  [PUBMED]
2.	Goodman's and Gillman's. The Pharmacological Basis of Therapeutics 10 th ed: Medical Publishing Division, 2001. p.13.  Back to cited text no. 2
3.	Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, et al. Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos 2003;31:439-46.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.	Ripp SL, Mills JB, Fahmi OA, Trevena KA, Liras JL, Maurer TS, et al. Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos 2006;34:1742-8.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]

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