Influence of selected Dietary Carotenoids on Retinol Deficiency Induced Biochemical Changes in Tissue Membranes of Rats

Vitamin A deficiency (VAD) is a major nutritional problem in India as well as almost 60
other countries (WHO, 2009). There are ~127 million and 4.4 million preschool children with
VAD (serum retinol < 0.70 mol/L) and xerophthalmia (dryness of the conjunctiva and cornea of
the eye), respectively. WHO (2005) has reported that >6 million women develop night blindness
during pregnancy annually. Approximately 45% of VAD and xerophthalmic children and
pregnant women with low-to-deficient vitamin A status live in South and South-East Asia.
Prevalence of VAD in India among preschool children is estimated to be 30.8%, while that of
xerophthalmia is 1.6%. Pregnant women (1.6%) in India are deficient in vitamin A while 12.1%
suffer from night blindness (West et al, 2002). VAD and its progress involve a variety of
physiological changes. Many functions of vitamin A such as vision, growth, reproduction, skin
health, immunity and erythropoiesis are affected in VAD. A general alteration in the physical
characteristics of cell membranes may be induced by VAD. Retinol deficiency has prooxidative
effect and increases the oxidative stress in cell membranes of rats (Kaul and Krishnakantha 1997).
The Governments of affected countries are trying to exterminate VAD by various means such as
administration of high but safe doses of synthetic vitamin A. Although VAD prophylaxis
programmes are in place in most of the affected countries, greater effort is needed to assess and
prevent VAD and its disorders (WHO, 2007). It is now widely accepted that alternate dietary
sources of nutrients are the sustainable answers to eradicate VAD and the associated disorders.
Vitamin A or retinol is available either in its preformed form (animal sources) or as
provitamin A carotenoids (plant sources) Provitamin A carotenoids include , - and -carotenes
and are cleaved to retinol by the carotenoid cleavage enzyme. Carotenoids with polar groups such
as hydroxyl, epoxide and keto groups are classified as xanthophylls and usually do not possess
provitamin A activity (except -cryptoxanthin) but are beneficial to health due to their
antioxidant properties (Krinsky, 1993). Even though plant foods containing carotenoids have
been used as dietary sources of vitamin A, its deficiency continues to be one of the major
nutritional problems in developing countries. This is mainly due to inadequate intake, improper
processing techniques, poor intestinal absorption and bioavailability. In addition, epidemiological
studies have established an inverse relationship between consumption of fruits and vegetables
rich in carotenoids and chronic degenerative diseases such as cancer, cardiovascular diseases,
neurodegenerative disorders, diabetes and age related macular degeneration (Williams et al.,
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2002; Bone et al., 2003). However, although the beneficial effects of the carotenoids are well
known, their absorption, metabolism and mechanism of action are poorly understood. To
understand the health benefit of carotenoids against VAD, it is important to have a better insight
into the bioavailability and metabolism of carotenoids under condition like VAD.
Carotenoid bioavailability is poor and only 10-20% of the carotenoids in a meal are
absorbed into circulation. Carotenoid bioavailability is affected by a variety of dietary and nondietary
factors, such as the matrix in which it is incorporated, the processing methods involved in
the preparation of the food, the nutrient status of the individual, amount and origin of dietary fat,
etc. (Erdman et al, 1993). In view of their multiple health benefits, research by many is focused
on determining factors that can improve carotenoid bioavailability (Deming et al., 2000; van het
Hoff et al., 2000). It is also important to determine the mechanism of action of different
carotenoids and to compare their effectiveness in modulating the changes caused by nutrient
deficiency.
-Carotene is cleaved by the intestinal -carotene monooxygenase either centrally or
excentrically to yield retinol. Besides retinol, apocarotenols are also reported to be formed from
-carotene (Barua and Olson, 2000). In lower vertebrates such as fish, xanthophylls such as lutein,
zeaxanthin, canthaxanthin, astaxanthin have exhibited provitamin A activity with the formation of
3’-dehydroretinol via reductive pathways (Moren et al., 2003; Matsuno, 1991; Goswami and
Barua, 1986). -Carotene is the most widely studied carotenoid by virtue of its provitamin A and
antioxidant properties. However, other carotenoids have also been of interest in recent times and
understanding their metabolism is of importance as well. Lutein for instance, plays an important
role in the prevention and management of age related macular degeneration (Krinsky and Johnson,
2005). However, the mechanism of antioxidant action of lutein and its metabolites is still largely
unknown. Since VAD results in increased oxidative stress (Anzulovich et al., 2000) in the cells,
and carotenoids are potent antioxidants, it would be of interest to study their effect on various
biochemical parameters at the cell membrane and tissue level. In view of this background, it was
proposed to investigate the possible provitamin A activity and antioxidant property of
xanthophyll carotenoids such as astaxanthin, lutein and fucoxanthin in comparison with -
carotene in retinol deficient (RD) rats in terms of formation of retinol and/or its related
compounds, and various biochemical parameters at the membrane and tissue level.