Protection of the Retina from Ischemia-Reperfusion Injury by L-Carnitine in Guinea Pigs

Abstract

Purpose

To investigate the efficacy of L-carnitine in preventing retinal injury followed by ischemia-reperfusion.

Methods

The eyes of 34 guinea pigs were used in this experiment. The guinea pigs were divided into two groups: the first group (n= 17) was given L-carnitine intraperitoneally (500mg/kg) and second group (n=17) received the same dose of saline solution. Under general anesthesia, peritomy was performed. Retro-orbital tissues were ligated for 90 minutes and ischemia was induced, followed by 4 hours of reperfusion. One of the enucleated eye was stained with hematoxylin and eosin (H&E) and retinal thicknesses were evaluated. Thiobarbituric acid reactive substances (TBARS) levels were determined in the retina of the other eye.

Results

Mean TBARS levels in retinal tissue were found lower in L-carnitine group (2.77 ± 0.55 μM) than in the control group (6.57 ± 1.19 μM), (p<0.01). On the other hand, mean retinal thickness was found to be increased in the control group (47.47 ± 5.62 μm) when compared to the L-carnitine group (26.52 ± 4.65 μm), (p<0.01). In correlation analysis, significantly positive relationships were found between retinal TBARS level and retinal thickness both in the control and L-carnitine groups (r=0.981, p<0.01 and r= 0.967, p<0.01 respectively).

Conclusions.

L-carnitine is effective in preventing retinal injury followed by ischemia-reperfusion.

Keywords

Ischemia-reperfusion L-carnitine TBARS Retinal edema

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References

Ducker

J.S.

. Vascular disorders, retinal arterial obstruction. In: Yanoff

Ducker

J.S.

, eds. Ophthalmology. London: Mosby 1999; 17: 1–8.

Ophir

Berenshtein

Kitrossky

Hydroxyl radical generation in the cat retina during reperfusion following ischemia.

Exp Eye Res 1993; 57: 351–7.

Kohner

E.M.

Chibber

. Retinal ischemia. In: Ryan

S.J.

Schachat

A.P.

, eds. Retina, vol 2. St. Louis: Mosby, 2001; 982–94.

Nayak

M.S.

Kita

Marmor

M.F.

. Protection of rabbit retina from ischemic injury by superoxide dismutase and catalase. Invest Ophthalmol Vis Sci 1993; 34: 2018–22.

Ophir

Berenshtein

Kitrossky

Averbukh

. Protection of the transiently ischemic cat retina by zinc-desferrioxamine. Invest Ophthalmol Vis Sci 1994; 35: 1212–6.

Agustin

A.J.

Spitnas

Koch

Grus

Lutz

. Effects of perfluorooctylbromide and vitamine E on ischemia induced retinal oxidative tissue damage. Exp Eye Res 1998; 66: 19–24.

Farber

J.L.

. Biology of the disease, membrane injury and calcium homeostasis in the pathogenesis of coagulative necrosis. Lab Invest 1982; 47: 114–23.

Anderson

R.E.

. Biochemistry and metabolism, free radicals and antioxidants. In: Hecht

K.A.

Straus

Denny

Taylor

Gamet

. eds. Fundamentals and Principles of Ophthalmology. San Francisco: Am Acad Ophthalmology 1999; 372–80.

Kim

S.Y.

Kwak

J.S.

Shin

J.P.

Lee

S.H.

. The protection of the retina from ischemic injury by the free radical scavenger Egb 761 and zinc in the cat retina. Ophthalmologica 1998; 212: 268–74.

10.

Halliwel

Gutteridge

J.M.C.

. Lipid peroxidation, oxygen radicals, cell damage and antioxidant therapy. Lancet 1984; 8391: 1396–2007.

11.

Siu

A.W.

Reiter

R.J.

C.H.

. Pineal indoleamines and vitamin E reduce nitric oxide-induced lipid peroxidation in rat retinal homogenates. J Pineal Res 1999; 27: 122–8.

12.

Uchiyama

Mihara

. Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Ann Biochem 1978; 86: 271–8.

13.

Swamy-Mruthinti

Lee Carter

. Acetyl-L-Carnitine decreases glycation of lens proteins: in vitro studies. Exp Eye Res 1999; 69: 109–15.

14.

Rosenthal

R.E.

Williams

Bogaert

Y.E.

Getson

P.R.

Fiskum

. Prevention of post ischemic canine neurologicai injury through potentiation of brain energy metabolism by acetyl-L-carnitine. Stroke 1992; 23: 1312–8.

15.

Szabo

E.M.

Droy-Lefaix

M.T.

Doly

Carre

Braquer

. Ischemia and reperfusion-induced histologic changes in the rat retina. Invest Ophthalmol Vis Sci 1991; 32: 1471–1478.

16.

Satoh

. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978; 90: 37–43.

17.

Slivka

Silbersweig

Pulsinelli

. Carnitine treatment for stroke in rats. Stroke 1990; 21: 808–11.

18.

Loster

Keller

Grommisch

Grunder

. Effects of L-carnitine and its acetyl and propionyl esters on ATP and PCr levels of isolated rat hearts perfused without fatty acids and investigated by means of 31P-NMR spectroscopy. Mol Cell Biochem 1999; 200: 93–102.

19.

Ferrari

Cucchini

Visioli

. The metabolic effects of L-camitine in angina pectoris. Int J Cardiol 1984; 5: 213–6.

20.

Stroh

Chrostoper

T.A.

Lopez

B.L.

Guo

Y.P.

Amico-Roxas

X.L.

. L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti-shock and endothelial protective effects in rat splanchnic ischemia-reperffision injury. Shock 1998; 9: 216–22.

21.

Cotter

M.A.

Cameron

N.E.

Keagan

Dines

K.C.

. Effects of acetyl- and proprionyl-L-Carnitine on peripheral nerve function and vascular supply in experimental diabetes. Metabolism 1995; 44: 1209–14.

22.

Bohan

T.P.

. Editorial comment. Stroke 1992; 23: 1317–8.

23.

Bellei

Battelli

Guarriero

D.M.

Changes in mitochondrial activity caused by ammonium salts and the protective effect of carnitine.

Biochem Biophys Res Commun 1989; 158: 181–8.

24.

Hansford

R.G.

. Control of mitochondrial substrate oxidation. Curr Topics Bioenerg 1980; 10: 217–78.

25.

Chida

Suziki

Nakanishi-Ueda

In vitro testing of antioxidants and biochemical end-points in bovine retinal tissue.

Ophthalmic Res 1999; 31: 407–15.

26.

Koudelova

Mourek

Drahota

Rauchova

. Protective effect of carnitine on lipoperoxide formation in rat brain. Physiol Res 1994; 43: 387–9.

27.

Palomba

Pes

G.M.

Demontis

M.P.

Varoni

M.V.

Deiana

Anania

. Metabolic and renal effects of Laevo-carnitine and propionyl-carnitine in rats with subtotal nephrecto-my. Pharmacol Res 1996; 34: 161–5.

28.

Kido

Tamai

Ohnari

Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier.

J Neurochem 2001; 79: 959–69.

29.

Nakanishi

Hatanaka

Huang

Na+- and C1 - coupled active transport of carnitine by the amino acid transporter ATB (0, ±) from mouse colon expressed in HRPE cells and Xenopus oocytes.

J Physiol 2001; 532: 297–304.

30.

Wawrzenczyk

Sacher

Mac

Nalecz

M.J.

Nalecz

K.A.

. Transport of L-carnitine in isolated cerebral cortex neurons. Eur J Biochem 2001; 268: 2091–8.