CYAN EXHIBIT 1018
`
`TITLE: The Action of Shrimp Oil (Penaeus foliaceus) on the Vitamin A Deficient
`White Rat
`
`Authors: GRANGAUD, Rene.; MASSONET, Renee.
`
`Journal: Comptes rendus de l'Academie des Sciences 1948 Vol. 227 pp. 568-570
`
`BIOLOGICAL CHEMISTRY. — The Action ofShrimp Oil (Penaeus foliaceus) on the Vitamin A
`
`Deficient White Rat. Note (*) by Mr. Rene Grangaud and Ms. Renee Massonet, presented by
`Mr. Maurice Javillier.
`
`Crustacean oil contains practically no vitamin A and is low in carotenes [(Lederer (1)], such that their
`effect on the growth of vitamin A deficient white rats is very minimal. Penaeus foliaceus oil, which
`
`we studied, is not an exception. On the other hand, its action on the development of xerophthalmia
`
`lesions was observed to be unexpected.
`
`Oil Preparation. —Cephalothoraxes from 1 kg of shrimp were emptied of their contents which were
`
`ground with anhydrous sodium sulfate then the mass was stripped using acetone (400 ml, then three
`
`times with 200 ml). The stripping liquids were collected in an ampule and diluted with water (250 ml)
`
`then petrol ether (300 mil). After agitation and rest, the etheropetrolic phase was separated and
`
`distilled under a nitrogen atmosphere with reduced pressure. The residue was an oil with a deep red
`
`color. The yield was on the order of 5 g of oil.
`
`The resulting product was administered to albino rats which, since they were weaned, had been fed
`
`with the regime deficient in vitamin A factors as specified by A. Chevallier (2). 16 rats from the same
`rearing, aged from 75 to 90 days and weighing from 60 to 70 grams with weight stabilisation of at
`
`least 10 days at the same time as an intense xerophthalmia, were divided into 3 lots (A, B and C).
`
`Each day, in addition to the base regime, each animal received the following: Lot A: (2 males, 3
`
`females): 90 mg of oil; Lot B (3 males, 2 females): 45 mg of oil; Lot C (3 males, 3 females): 22 mg of
`
`oil. In parallel, three control lots (D, E and F) with signs of deficiency, in all points comparable to
`
`those of the preceding lots, received the following on a daily basis:
`
`(*) Meeting of 30 August 1948.
`(1) Bull. Soc. Chim. biol., 20, 1938, p. 567.
`(2) G. H. ROGER and Leon BINET, Traite de Physiologie normale et pathologique, 22, (supp), p.
`237.
`
`568
`
`

`
`Lot D (2 males, 3 females): base regime + 15 IU of vitamin A; Lot E (2 males, 2 females): base
`
`regime + 4 IU of vitamin A; Lot F (3 males, 3 females): base regime without any addition of vitamin
`A.
`
`The five animals in Lot D quickly reached a normal growth rate, showing that the lesions had not
`
`reached an irreversible stage. Lot E also started to grow but much more slowly and one of the two
`died on the 99th day, 24 hours after having received the first dose of vitamin. Finally, the six Lot F
`animals died before the 100th day, i.e., 15 to 25 days after the appearance of the first signs of
`deficiency.
`
`Among the animals which received the shrimp oil, only those in Lot A quickly reached a normal
`
`growth rate. In Lot B, weight gain was much slower and three of them died, 22, 30 and 38 days after
`
`the first administration of oil. Two, more robust animals reached weights of 127 g and 138 g and
`survived beyond the 125th day but had signs of physiological distress including, in particular, paralysis
`of the hindquarters. Lot C, which gained practically no weight, all died in less than 35 days after the
`
`appearance of the first signs of deficiency.
`
`These results were not surprising: in all likelihood, the carotene traces present in the shrimp oil were
`
`responsible for the recorded growth action. After this action, there was an unappreciable or hardly
`
`detectable effect on the development of the xerophthahnia lesions in the animals of lots B and C. It is
`
`evident that the healing of these lesions was slower than the weight gain and a daily dose of 4
`
`micrograms of carotene, though clearly greater than the maintenance dose [Mr. Javillier and Ms.
`
`Emerique (3)] and sufficient to re-establish growth, only allowed healing ofthe xeroplztlzalmia [Ms L.
`
`Random and R. Netter (4)]. However, among the 16 rats which received the shrimp oil, only those in
`Lot A could find their daily ration of carotene in the order of 4 micrograms. However, the 16 animals,
`
`without exception, were healed from their xerophthalmia; 14 of them in less than 10 days, 2 which
`
`had more severe cases, in 15 days. Undeniable improvement was always seen in the four days
`
`following the first administration of oil (5).
`
`(3) Bull. Soc. Chim. biol., 13, 1931, p. 771.
`(4) Bull. Soc. Chim. biol., 15, 1933, p. 706.
`(5) Our results should be compared with those recently published by P. Dubouloz, R. Merville C.
`Chevalier (Bull. Soc. Chim Biol, 30, 1948, p. 112). These authors, administering to rats deficient in
`vitamin A a regime incapable of restoring growth, found that remaining characteristics of eye injuries
`were significantly decreased.
`
`569
`
`

`
`At the same time, in the control animals, only Lot D (15 IU pro die vitamin A) were healed of
`
`xerophthalmia; the healing was, however, overall, a little slower than in the rats which received
`
`shrimp oil. The lesions in the Lot E animals (4 IU “pro die” vitamin A) were still in full development
`
`and had not discemibly improved three weeks after the first administration of vitamin. Finally, all the
`
`Lot F rats died with signs of intense xerophthalmia.
`
`It is evident from these experiments that oil extracted from decapod crustaceans, Penaeus foliaceus,
`
`caught in the Mediterranean, exhibit a much more evident antixerophthalmic action which its action
`
`on the white rat’s growth could not be used to predict. The carotene traces could not alone be
`
`responsible for this action. It is, therefore, likely that, in this oil, there is a constituent, other than the
`
`carotenes and vitamin A, which play a role in the antixerophthalmic activity.
`
`570