Pineal indoleamines and vitamin E reduce nitric oxide‐induced lipid peroxidation in rat retinal homogenates

Abstract

Oxidative damage to retinal cell membranes can lead to sight-threatening ocular diseases. Pineal indoleamines are naturally located and synthesized in the retina, and they possibly protect the retina from oxidative cell damage. In this study, we compared the efficacy of three different pineal indoleamines (melatonin, N-acetylserotonin, and pinoline) with vitamin E, a well-known antioxidant, against nitric oxide (NO)-induced lipid peroxidation (LPO) in rat retinal homogenates. The possible synergistic effect of these agents was also studied. Retinal homogenates were incubated with sodium nitroprusside, which releases NO*. The LPO product, malondialdehyde (MDA), provided an index of cell damage. The results show that vitamin E and indoleamines significantly reduced MDA levels in a dose-dependent manner. When vitamin E was combined with the indoleamines, the protection was synergistically enhanced. In summary, under conditions where cellular homogenates are used (a) vitamin E and the three pineal indoleamines protected the retinal cells from NO-induced LPO damage; (b) the efficacies of each of these compounds had the following relationships: vitamin E > N-acetylserotonin > pinoline > melatonin; (c) vitamin E acted synergistically with indoleamines in combating oxidative retinal damage. Whether these same associations would exist in vivo after treatment with these compounds is unknown. The pharmacological potential of indoleamines, possibly in combination with vitamin E, in preventing retinal pathogenesis deserves further investigation.

Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor

“…Indeed, previous studies have shown a possible role for retinal melatonin as a free radical scavenger within photoreceptors. In isolated photoreceptors from frog retina, melatonin was approximately100 times more potent than vitamin E in inhibiting light-induced oxidative processes (32) and melatonin can reduce the lipid peroxidation induced by nitric oxide in rat retinal homogenates (33). However, supraphysiological concentrations of melatonin may be needed for the antioxidant actions, and MT1 receptor activation appears to play a dominant role in maintaining cell viability.…”

Actions of Melatonin in the Reduction of Oxidative Stress

“…The efficiency of any agent that destroys macromolecules by processes involving free radicals should be decreased if antioxidants, including melatonin, are also present. This has been shown to be the case with melatonin; it has been effectively utilized in vitro and in vivo to combat an incredibly wide number of toxicants including peroxynitrite [22][23][24]65], indomethacin [3], alloxan [26], cisplatin [51], glutamate [29], carbon tetrachloride [62], adriamycin [60], hydrogen peroxide [96], amyloid ß protein [72,73], carrageenan [22][23][24], cerulein [83], nitrilotriacetate [82] and many others [35,87,93,99]. Melatonin has proven equally effective in reducing oxidative damage in conditions where free radical involvement has been established; such situations include ischemia/reperfusion injury [22,111], biliary obstruction [59], ionizing radiation [110], etc.…”

Melatonin and Its Analog 5-Methoxycarbonylamino-N-Acetyltryptamine Potentiate Adrenergic Receptor-Mediated Ocular Hypotensive Effects in Rabbits: Significance for Combination Therapy in Glaucoma

“…One molecule with interesting neuroprotective actions and ocular hypotensive effects is melatonin (N-acetyl-5-methoxytryptamine) (Rowland et al, 1981;Siu et al, 1999;Siu et al, 2006;Alarma-Estrany et al, 2007). This molecule and some of its derivatives produce a marked reduction in IOP when topically applied (Pintor et al, 2001(Pintor et al, , 2003Serle et al, 2004;Ismail and Mowafi, 2009;Alarma-Estrany et al, 2008, 2011.…”