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Updated: Jun 8, 2026
Characterization of Molecular Mechanisms of In vivo UVR Induced Cataract
Published on: November 28, 2012
Targeting CYP450 modulation to decrease the risk of induced cataract in the experimental model
D V Patel1, T R Gandhi, K V Patel
1Department of Pharmacology, Anand Pharmacy College, SPU, Anand, India. dip_apc@yahoo.co.in
Background:
Diabetes is one of the major causes of cataract. Some drugs prescribed for the treatment of diabetes are the modulators of CYP450, which may alter the risk of cataract.
Objective:
To study the effect of CYP450 modulation in galactosemic cataract.
Materials And Methods:
Male Sprague-Dawley suckling rats were allotted to four groups (n = 6), as follows: Group 1: Normal control, Group 2: Galactose control, Group 3: CYP450 inhibitor pretreated and Group 4: CYP450 inducer pretreated. Cataract was induced in animals of all groups except group 1 by feeding them galactose (50%), 21 days after parturition. From the eighteenth day of life, CYP450 inhibitor (nifedipine; 8.1 mg/kg) and CYP450 inducer (pioglitazone; 3.8 mg/kg) were given orally to groups 3 and 4, respectively. The maturation pattern of the cataract was observed by an operating microscope, every third day. Biochemical changes in the lenses of all groups, for example, CYP450 activity expressed as ΅M NADPH oxidized / unit time, alterations in the levels of total proteins, soluble proteins, and reduced glutathione (GSH) following the induction of cataract, were estimated.
Results:
The microscopic examination of the lenses indicated that CYP450 inhibitor pre-treatment delayed (fourteenth day) the occurrence of cataract, while CYP450 inducer pretreatment demonstrated an early (ninth day) cataract as compared to galactose control rats (twelfth day). A significant decrease and increase in CYP450 activity was observed with the CYP450 inhibitor and inducer pre-treatment, respectively. There was no alteration in the GSH level, but a significant increase in total and soluble protein was found in groups 3 and 4 as compared to group 2.
Conclusion:
CYP450 may have a role in the initiation of cataract without any effect on the maturation pattern, as revealed by the delayed occurrence of cataract with the CYP450 inhibitor and an early onset of cataract with the CYP450 inducer.
Insights
CYP450 enzyme modulation influences cataract development. Inhibitors delayed cataract onset, while inducers accelerated it, suggesting a role in cataract initiation.
Area of Science:
- Biochemistry
- Ophthalmology
- Pharmacology
Background:
- Diabetes mellitus is a primary risk factor for cataract formation.
- Certain diabetes medications modulate Cytochrome P450 (CYP450) enzymes, potentially impacting cataract risk.
Purpose of the Study:
- To investigate the influence of CYP450 modulation on galactose-induced cataract development.
- To assess the impact of CYP450 inhibitors and inducers on cataract initiation and progression.
Main Methods:
- Galactosemic cataract was induced in Sprague-Dawley rats.
- Rats were pretreated with a CYP450 inhibitor (nifedipine) or inducer (pioglitazone).
- Cataract progression and biochemical lens changes (CYP450 activity, proteins, glutathione) were analyzed.
Main Results:
- CYP450 inhibitor pretreatment delayed cataract occurrence; inducer pretreatment accelerated it compared to controls.
- CYP450 activity was significantly decreased by the inhibitor and increased by the inducer.
- Reduced glutathione levels remained unchanged, but total and soluble proteins increased.
Conclusions:
- CYP450 enzymes appear to play a role in the initiation of cataract.
- Modulation of CYP450 activity affects the onset of cataract but not its maturation pattern.
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