4-Hydroxynonenal-induced cataract

Role of lipid aldehydes in cataractogenesis

Naseem Ansari, Satish Srivastava

Research output: Contribution to journalArticle

Abstract

Purpose: To investigate the detoxification mechanisms of the most toxic lipid aldehyde, 4-hydroxynonenal (HNE) and its role in hyperglycemic cataract. Methods: HNE conjugates with GSH spontaneously or catalysed by glutathione S-transferases. Reduction of HNE and HNE-GS conjugate by homogenous preparation of bovine lens aldose reductase (AR) was studied. In-vitro cataracts were developed by culturing rat lenses in 50 mM glucose or 50 μM HNE. Antioxidant, trolox (100 μM) and AR inhibitor, sorbinil (50 μM) were also included in some cultures. Lenticular opacification was assessed by digital image analysis. Results: Lens AR efficiently reduced HNE and HNE-GS in the presence of NADPH (Km HNE ≃ 9 μM; Km HNE-GS ≃ 30 μM). In lenses cultured under hyperglycemic conditions, both trolox and sorbinil had protective effect as reported. In lenses cultured with HNE, the decrease in transmitted light was 43, 65, and 87% on days 3, 5, and 8, respectively. Trolox ameliorated whereas sorbinil accelerated the progression of HNE catarat. Conclusions: (1) HNE and HNE-GS are excellent substrates for AR, (2) HNE is cataractogeneic; antioxidant ameliorates the cataractogenic effect of glucose and HNE, possibly by stabilizing the membrane and increasing the antioxidation capacity of the lens (3) Sorbinil ameliorates the cataractogenic effect of glucose by inhibiting AR and sparing NADPH which would increase the antioxidant capacity and (4) HNE-cataract is accelerated by sorbinil because it inhibits AR-mediated HNE detoxification.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996
Externally publishedYes

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Aldehyde Reductase
Aldehydes
Cataract
Lenses
Lipids
Antioxidants
NADP
Glucose
Poisons
Glutathione Transferase
4-hydroxy-2-nonenal
sorbinil
Light
Membranes
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid

ASJC Scopus subject areas

  • Ophthalmology

Cite this

4-Hydroxynonenal-induced cataract : Role of lipid aldehydes in cataractogenesis. / Ansari, Naseem; Srivastava, Satish.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

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