23 replies to this topic

[tunt01]

http://www.scienceda...90622064807.htm

Melatonin: The Fountain Of Youth?

ScienceDaily (June 22, 2009) — Melatonin can slow down the effects of aging. A team at laboratoire Arago in Banyuls sur Mer (CNRS / Université Pierre et Marie Curie) has found that a treatment based on melatonin can delay the first signs of aging in a small mammal.

Better known as the ‘time-keeping' hormone, melatonin is naturally secreted by the body during the night. It is therefore a kind of biological signal for nightfall, allowing an organism to synchronize itself with the day/night rhythm. At Laboratoire Arago, Elodie Magnanou and her co-workers studied the long-term effects of melatonin on the Greater White-toothed shrew, a small nocturnal insectivorous mammal. Under normal conditions, this animal shows the first signs of aging after reaching 12 months, mainly through the loss of circadian rhythm in its activities. By continuously administering melatonin, starting a little before 12 months, the appearance of these first signs was delayed by at least 3 months, which is a considerable period in relation to the lifespan of this shrew*.

Melatonin is now known to play several beneficial roles. These include being an antioxidant, an anti-depressant, and helping to remediate sleep problems. The next step will be to understand the mode of action of the hormone on aging, so we can perhaps envisage its use on humans.

These results appeared in the journal PLoS One on 15 June 2009.

*The Greater White-toothed shrew has a lifespan of 12 to 18 months in the wild and up to 30 months in captivity. Captivity does not change the time at which signs of aging appear, it simply lengthens life.

Edited by Mind, 28 June 2009 - 01:41 AM.
changed title

[Athanasios]

From the research that I am aware of, melatonin does not extend maximum lifespan but extends average lifespan by 'squaring the mortality curve'. This research here shows what you would expect, an average delay in age-related disability.

Thanks for the article!

[tunt01]

you know... as soon as i cut/paste this thing in, i realized i mis-typed the thread title.

you are right. it should say "delays signs of aging" not "extends lifespan".

[Athanasios]

you know... as soon as i cut/paste this thing in, i realized i mis-typed the thread title.

you are right. it should say "delays signs of aging" not "extends lifespan".

Ha, no worries. I usually have to edit my posts to correct or clarify. No matter how many times I proof read them, it seems I always find a reason to edit.

One thing interesting about the article is how it seemed to square the curve even though melatonin was administered only right before age-related disabilities usually occur.

It is these type of examples that make me think that the best time to start CR is when you are in your 50s, best in terms of least opportunity cost per likely years of extension. While, I understand that CR benefits max lifespan relative to the amount of time on it, I am just not convinced that the probability of being one of the later survivors is worth doing CR when young. In other words, late started CR seems to pick the low hanging fruit quite well.

Edited by cnorwood, 22 June 2009 - 07:06 PM.

[seekonk]

While, I understand that CR benefits max lifespan relative to the amount of time on it, ...

You say that like it is a known known...

Wouldn't be the first time I missed the memo, but...

[Dmitri]

you know... as soon as i cut/paste this thing in, i realized i mis-typed the thread title.

you are right. it should say "delays signs of aging" not "extends lifespan".

Interesting, What age do humans begin to show signs of aging? It might be too late for some, right? Also, how safe is it to use long term wouldn't the body get used to getting it through supplements and work less efficiently if you stopped supplementation?

[shaggy]

I think melatonin is a valuable supplement but I'm still cautious on its effiicacy in retarding artherosclerosis...for example:-

http://www.ingentaco...000003/art00336

[tunt01]

Interesting, What age do humans begin to show signs of aging? It might be too late for some, right? Also, how safe is it to use long term wouldn't the body get used to getting it through supplements and work less efficiently if you stopped supplementation?

1. signs of aging. not sure. different for different people... i guess broadly speaking in your 30's.

2. pretty sure melatonin improves deep sleep and the release of growth hormone. this accelerates healing/repair, decelerates the signs of aging. life extension properties... not sure. if you have sleeping problems, constantly travel/suffer from jet lag, work a night shift... maybe melatonin is attractive at maximizing your own lifespan. in these scenarios, we would assume your own body's release is disrupted in some fashion.

i have tried a melatonin/theanine pill. it was efficacious but i don't find it to be necessary on a consistent basis.

Edited by prophets, 22 June 2009 - 08:11 PM.

[sUper GeNius]

you know... as soon as i cut/paste this thing in, i realized i mis-typed the thread title.

you are right. it should say "delays signs of aging" not "extends lifespan".

Interesting, What age do humans begin to show signs of aging? It might be too late for some, right?

I'd say very early, maybe in late teens, certainly by early to mid twenties. I remember reading about autopsies being performed on 18 yr old American soldiers, I think in Korea. A large percentage of them already had plaque buildup in their coronary arteries. I guess it all depends on your definition of aging.

[seekonk]

I'd say very early, maybe in late teens, certainly by early to mid twenties. I remember reading about autopsies being performed on 18 yr old American soldiers, I think in Korea. A large percentage of them already had plaque buildup in their coronary arteries. I guess it all depends on your definition of aging.

I am sure that in addition to arterial plaque, they also had plaque buildup on their teeth. I wouldn't call either intrinsic aging.

[niner]

I'd say very early, maybe in late teens, certainly by early to mid twenties. I remember reading about autopsies being performed on 18 yr old American soldiers, I think in Korea. A large percentage of them already had plaque buildup in their coronary arteries. I guess it all depends on your definition of aging.

I am sure that in addition to arterial plaque, they also had plaque buildup on their teeth. I wouldn't call either intrinsic aging.

How would you define it? A lot of people seem to think that graying of hair and photoaging of skin is the bulk of it. I don't agree with them, though I'd be happy to avoid or reverse those conditions. IMO, the first molecular symptoms of aging, such as crosslinking of proteins, occur shortly after conception. The processes of aging are intrinsic to our biology, although we can slow them down with e.g. CR or improved glucose control. These processes are happening the entire time we are alive, thus our interest in methods (e.g. SENS) that might repair the molecular lesions involved. If you only define "signs of aging" as something you can see, then you are in the "hair and skin is everything" camp I guess.

[Athanasios]

While, I understand that CR benefits max lifespan relative to the amount of time on it, ...

You say that like it is a known known...

Wouldn't be the first time I missed the memo, but...

Yes, thanks for the clarification. In mice, the max lifespan benefit is relative to the amount of time on CR, and this seemingly carries over to some primates as well.

What we have seen with CR, in humans, does support the notion that it at least helps square the curve. This is my main goal in trying out lifestyle changes that affect longevity. Examples like this melatonin study make me think I can cherry pick the timing to get the most prevention of premature death with the least opportunity cost. If it extends max lifespan, that will just be the sugar free icing on the low cal cake (by still giving 50% of the max lifespan benefit).

Edited by cnorwood, 22 June 2009 - 09:28 PM.

[seekonk]

I am sure that in addition to arterial plaque, they also had plaque buildup on their teeth. I wouldn't call either intrinsic aging.

If you only define "signs of aging" as something you can see, then you are in the "hair and skin is everything" camp I guess.

Not at all. You can see dental plaque, but few people would seriously suggest that this is a sign of aging. As far as I understand, arterial plaque, like dental plaque, is to a large extent avoidable, and apparently to some extent even reversible, and would IMO fall in the same category, namely, conditions that may be statistically associated with older people but that are not intrinsic to aging.

Edited by seekonk, 22 June 2009 - 09:47 PM.

[sUper GeNius]

I am sure that in addition to arterial plaque, they also had plaque buildup on their teeth. I wouldn't call either intrinsic aging.

If you only define "signs of aging" as something you can see, then you are in the "hair and skin is everything" camp I guess.

Not at all. You can see dental plaque, but few people would seriously suggest that this is a sign of aging.

Few would compare dental plaque to arterial plaque. There are significant differences. I can rid myself of dental plaque in 15 minutes. I can *easily* prevent it in the first place. The same can't be said for arterial plaque.

[seekonk]

I am sure that in addition to arterial plaque, they also had plaque buildup on their teeth. I wouldn't call either intrinsic aging.

If you only define "signs of aging" as something you can see, then you are in the "hair and skin is everything" camp I guess.

Not at all. You can see dental plaque, but few people would seriously suggest that this is a sign of aging.

Few would compare dental plaque to arterial plaque. There are significant differences. I can rid myself of dental plaque in 15 minutes. I can *easily* prevent it in the first place. The same can't be said for arterial plaque.

The fact that it is more difficult to get at arterial plaque than dental plaque is a difference in degree, not substance. I don't dispute that it may be difficult for you to prevent arterial plaque, and that it would be nice to have a cure. That does not make it intrinsic to aging. Rather, like the accumulation of dental plaque, arterial plaque is largely a consequence of behaviour. Many people find it very difficult to avoid weight gain and type II diabetes, or to stop smoking, as they get older. That does not mean that aging causes weight gain, diabetes, or lung cancer.

As for arterial plaque in teens, which was the example you raised as a sign of aging, I would actually disagree your contention that it is not easily preventable. I strongly suspect that arterial plaque is easily preventable in teens.

Edited by seekonk, 22 June 2009 - 10:30 PM.

[Ben K]

"Under normal conditions, this animal shows the first signs of aging after reaching 12 months, mainly through the loss of circadian rhythm in its activities."

So the main "sign of aging" this study tested for was a loss of circadian rhythm in the animal's activity? Considering that's exactly what melatonin regulates, it's hard to see how you can generalize that specific benefit to aging in general.

Unless I'm missing something, it's sort of like saying that coffee delays signs of aging in animals that tend to get sleepy during the day as they get older.

[Athanasios]

Unless I'm missing something, it's sort of like saying that coffee delays signs of aging in animals that tend to get sleepy during the day as they get older.

No, I think you are right. Here is the paper:
http://www.plosone.o...al.pone.0005904


An interesting note:
"Conversely, implanting aged animals that had lost rhythmic activity was ineffective (not shown). This would indicate that once disorganized, locomotor activity rhythm cannot be rescued; melatonin only serves to maintain an existing rhythm."

and
"Mortality was not significantly affected by the melatonin treatment..."

[Dmitri]

Interesting, What age do humans begin to show signs of aging? It might be too late for some, right? Also, how safe is it to use long term wouldn't the body get used to getting it through supplements and work less efficiently if you stopped supplementation?

1. signs of aging. not sure. different for different people... i guess broadly speaking in your 30's.

2. pretty sure melatonin improves deep sleep and the release of growth hormone. this accelerates healing/repair, decelerates the signs of aging. life extension properties... not sure. if you have sleeping problems, constantly travel/suffer from jet lag, work a night shift... maybe melatonin is attractive at maximizing your own lifespan. in these scenarios, we would assume your own body's release is disrupted in some fashion.

i have tried a melatonin/theanine pill. it was efficacious but i don't find it to be necessary on a consistent basis.

I see, I now remember that I had read about aging in the 30s from the following study:

http://www.ncbi.nlm....Pubmed_RVDocSum

Supplementation with CoQ10 lowers age-related (ar) NOX levels in healthy subjects.

Morré DM, Morré DJ, Rehmus W, Kern D.
Department of Foods and Nutrition, Purdue University, West Lafayette, IN, USA. morredm@purdue.edu
Our work has identified an aging-related ECTO-NOX activity (arNOX), a hydroquinone oxidase which is cell surface located and generates superoxide. This activity increases with increasing age beginning >30 y. Because of its cell surface location and ability to generate superoxide, the arNOX proteins may serve to propagate an aging cascade both to adjacent cells and to oxidize circulating lipoproteins as significant factors determining atherogenic risk. The generation of superoxide by arNOX proteins is inhibited by Coenzyme Q10 as one basis for an anti-aging benefit of CoQ10 supplementation in human subjects. In a preliminary pilot study, 25 female subjects between 45 and 55 y of age were recruited at Stanford University from the Palo Alto, CA area. Informed consent was obtained. Ten of the subjects received Coenzyme Q10 supplementation of 180 (3 x 60 mg) per day for 28 days. Serum, saliva and perspiration levels of arNOX were determined at 7, 14 and 28 days of CoQ10 supplementation and compared to the initial baseline value. Activity correlated with subject age up to a maximum between age 50 and 55 years of age for saliva and perspiration as well and then declined. With all three sources, the arNOX activity extrapolated to zero at about age 30. Response to Coenzyme Q10 also increased with age being least between ages 45 and 50 and greatest between ages 60 and 65. With all three biofluids, arNOX activity was reduced between 25 and 30% by a 3 x 60 mg daily dose Coenzyme Q10 supplementation. Inhibition was the result of Coenzyme Q10 presence.

[tunt01]

pretty worthwhile tidbits i think.

Melatonin at night and ALCAR/RALA during the day seem ideal for mitochondria performance...

http://www.ncbi.nlm....pubmed/19054298

Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production.

López A, García JA, Escames G, Venegas C, Ortiz F, López LC, Acuña-Castroviejo D.
Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain.
The role of melatonin in improving mitochondrial respiratory chain activity and increasing ATP production in different experimental conditions has been widely reported. To date, however, the mechanism(s) involved are largely unknown. Using high-resolution respirometry, fluorometry and spectrophotometry we studied the effects of melatonin on normal mitochondrial functions. Mitochondria were recovered from mouse liver cells and incubated in vitro with melatonin at concentrations ranging from 1 nm to 1 mm. Melatonin decreased oxygen consumption concomitantly with its concentration, inhibited any increase in oxygen flux in the presence of an excess of ADP, reduced the membrane potential, and consequently inhibited the production of superoxide anion and hydrogen peroxide. At the same time it maintained the efficiency of oxidative phosphorylation and ATP synthesis while increasing the activity of the respiratory complexes (mainly complexes I, III, and IV). The effects of melatonin appeared to be due to its presence within the mitochondria, since kinetic experiments clearly showed its incorporation into these organelles. Our results support the hypothesis that melatonin, together with hormones such as triiodothyronine, participates in the physiological regulation of mitochondrial homeostasis.


http://www.ncbi.nlm....pubmed/19437546

Melatonin and its brain metabolite N(1)-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian mice.

Tapias V, Escames G, López LC, López A, Camacho E, Carrión MD, Entrena A, Gallo MA, Espinosa A, Acuña-Castroviejo D.
Centro de Investigación Biomédica, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
Melatonin prevents mitochondrial failure in models of sepsis through its ability to inhibit the expression and activity of both cytosolic (iNOS) and mitochondrial (i-mtNOS) inducible nitric oxide synthases. Because Parkinson's disease (PD), like sepsis, is associated with iNOS induction, we assessed the existence of changes in iNOS/i-mtNOS and their relation with mitochondrial dysfunction in the MPTP model of PD, which also displays increased iNOS expression. We also evaluated the role of melatonin (aMT) and its brain metabolite, N(1)-acetyl-5-methoxykynuramine (AMK), in preventing i-mtNOS induction and mitochondrial failure in this model of PD. Mitochondria from substantia nigra (SN) and, to a lesser extent, from striatum (ST) showed a significant increase in i-mtNOS activity, nitrite levels, oxidative stress, and complex I inhibition after MPTP treatment. MPTP-induced i-mtNOS was probably related to mitochondrial failure, because its prevention by aMT and AMK reduced oxidative/nitrosative stress and restored complex I activity. These findings represent the first experimental evidence of a potential role for i-mtNOS in the mitochondrial failure of PD and support a novel mechanism in the neuroprotective effects of aMT and AMK. © 2009 Wiley-Liss, Inc.


http://www.ncbi.nlm....pubmed/18928424

Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection.

Petrosillo G, Fattoretti P, Matera M, Ruggiero FM, Bertoni-Freddari C, Paradies G.
Department of Biochemistry and Molecular Biology, CNR Institute of Biomembranes and Bioenergetics, University of Bari, Bari Italy.
Reactive oxygen species (ROS) are considered a key factor in brain aging process. Complex I of the mitochondrial respiration chain is an important site of ROS production and hence a potential contributor to brain functional changes with aging. Appropriate antioxidant strategies could be particularly useful to limit this ROS production and associated mitochondrial dysfunction. Melatonin has been shown to possess antioxidant properties and to reduce oxidant events in brain aging. The mechanism underlying this protective effect of melatonin is not well established. In the present study, we examined the effects of long-term treatment of aged rats with melatonin on various parameters related to mitochondrial bioenergetics in brain tissue. After isolation of mitochondria from control, aged, and melatonin-treated young and aged rats, various bioenergetic parameters were evaluated such as complex I activity, rates of state 3 respiration, mitochondrial hydrogen peroxide (H2O2) production, and membrane potential. The mitochondrial content of normal and oxidized cardiolipin was also evaluated. We found that all these mitochondrial parameters were significantly altered with aging, and that melatonin treatment completely prevented these age-related alterations. These effects appear to be due, at least in part, to melatonin's ability to preserve the content and structural integrity of cardiolipin molecules, which play a pivotal role in mitochondrial bioenergetics. The melatonin's ability to prevent complex I dysfunction and cardiolipin peroxidation was also demonstrated by in vitro experiments on brain mitochondria treated with tert-butyl hydroperoxide. In summary, this study documents a decline of mitochondrial bioenergetic functions in brain with aging and the beneficial effect of melatonin.

[Dmitri]

pretty worthwhile tidbits i think.

Melatonin at night and ALCAR/RALA during the day seem ideal for mitochondria performance...

http://www.ncbi.nlm....pubmed/19054298

Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production.

López A, García JA, Escames G, Venegas C, Ortiz F, López LC, Acuña-Castroviejo D.
Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Granada, Spain.
The role of melatonin in improving mitochondrial respiratory chain activity and increasing ATP production in different experimental conditions has been widely reported. To date, however, the mechanism(s) involved are largely unknown. Using high-resolution respirometry, fluorometry and spectrophotometry we studied the effects of melatonin on normal mitochondrial functions. Mitochondria were recovered from mouse liver cells and incubated in vitro with melatonin at concentrations ranging from 1 nm to 1 mm. Melatonin decreased oxygen consumption concomitantly with its concentration, inhibited any increase in oxygen flux in the presence of an excess of ADP, reduced the membrane potential, and consequently inhibited the production of superoxide anion and hydrogen peroxide. At the same time it maintained the efficiency of oxidative phosphorylation and ATP synthesis while increasing the activity of the respiratory complexes (mainly complexes I, III, and IV). The effects of melatonin appeared to be due to its presence within the mitochondria, since kinetic experiments clearly showed its incorporation into these organelles. Our results support the hypothesis that melatonin, together with hormones such as triiodothyronine, participates in the physiological regulation of mitochondrial homeostasis.


http://www.ncbi.nlm....pubmed/19437546

Melatonin and its brain metabolite N(1)-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian mice.

Tapias V, Escames G, López LC, López A, Camacho E, Carrión MD, Entrena A, Gallo MA, Espinosa A, Acuña-Castroviejo D.
Centro de Investigación Biomédica, Instituto de Biotecnología, Universidad de Granada, Granada, Spain.
Melatonin prevents mitochondrial failure in models of sepsis through its ability to inhibit the expression and activity of both cytosolic (iNOS) and mitochondrial (i-mtNOS) inducible nitric oxide synthases. Because Parkinson's disease (PD), like sepsis, is associated with iNOS induction, we assessed the existence of changes in iNOS/i-mtNOS and their relation with mitochondrial dysfunction in the MPTP model of PD, which also displays increased iNOS expression. We also evaluated the role of melatonin (aMT) and its brain metabolite, N(1)-acetyl-5-methoxykynuramine (AMK), in preventing i-mtNOS induction and mitochondrial failure in this model of PD. Mitochondria from substantia nigra (SN) and, to a lesser extent, from striatum (ST) showed a significant increase in i-mtNOS activity, nitrite levels, oxidative stress, and complex I inhibition after MPTP treatment. MPTP-induced i-mtNOS was probably related to mitochondrial failure, because its prevention by aMT and AMK reduced oxidative/nitrosative stress and restored complex I activity. These findings represent the first experimental evidence of a potential role for i-mtNOS in the mitochondrial failure of PD and support a novel mechanism in the neuroprotective effects of aMT and AMK. © 2009 Wiley-Liss, Inc.


http://www.ncbi.nlm....pubmed/18928424

Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection.

Petrosillo G, Fattoretti P, Matera M, Ruggiero FM, Bertoni-Freddari C, Paradies G.
Department of Biochemistry and Molecular Biology, CNR Institute of Biomembranes and Bioenergetics, University of Bari, Bari Italy.
Reactive oxygen species (ROS) are considered a key factor in brain aging process. Complex I of the mitochondrial respiration chain is an important site of ROS production and hence a potential contributor to brain functional changes with aging. Appropriate antioxidant strategies could be particularly useful to limit this ROS production and associated mitochondrial dysfunction. Melatonin has been shown to possess antioxidant properties and to reduce oxidant events in brain aging. The mechanism underlying this protective effect of melatonin is not well established. In the present study, we examined the effects of long-term treatment of aged rats with melatonin on various parameters related to mitochondrial bioenergetics in brain tissue. After isolation of mitochondria from control, aged, and melatonin-treated young and aged rats, various bioenergetic parameters were evaluated such as complex I activity, rates of state 3 respiration, mitochondrial hydrogen peroxide (H2O2) production, and membrane potential. The mitochondrial content of normal and oxidized cardiolipin was also evaluated. We found that all these mitochondrial parameters were significantly altered with aging, and that melatonin treatment completely prevented these age-related alterations. These effects appear to be due, at least in part, to melatonin's ability to preserve the content and structural integrity of cardiolipin molecules, which play a pivotal role in mitochondrial bioenergetics. The melatonin's ability to prevent complex I dysfunction and cardiolipin peroxidation was also demonstrated by in vitro experiments on brain mitochondria treated with tert-butyl hydroperoxide. In summary, this study documents a decline of mitochondrial bioenergetic functions in brain with aging and the beneficial effect of melatonin.

Interesting abstracts, I'll think about adding Melatonin and CoQ10 + Vitamin E (both seem to work well together) in about 5 years when I turn 30; at the time superoxide begins to increase as mentioned in the CoQ10 study I posted. Hopefully in 5 years they'll be a lot more studies showing the benefits and safety of those supplements (mentioned in your studies).

[100YearsToGo]

Female cba mice don't seem to like melatonin a lot. Although it increase their lifespan too.
http://biomed.geront...print/56/7/B311

[JLL]

Female cba mice don't seem to like melatonin a lot. Although it increase their lifespan too.
http://biomed.geront...print/56/7/B311

So the animals on melatonin lived longer but had more fatal tumors. What did the control mice die of?

[100YearsToGo]

So the animals on melatonin lived longer but had more fatal tumors. What did the control mice die of?

Old age?

Table 10 only tells us that 3 from the control group died of fatal tumors while the same fatal malady affected 13 of the melatonin group.

However, they also mention that other studies that used other lines (C3H) of female mice did not report these results. Male mice are not safe either. At least depending on the line used.

"Lipman and colleagues (31) observed lymphomas in 77.9% of male C57BL/6 mice that received melatonin with food (11 ppm or 68 mg/kg) from the age of 18 months to 50% survival at 26.5 months, whereas in control groups only 28.6% mice developed lymphomas. Leukemias were detected in 70–98% of C57BL/6 mice and in 78% of CC57Br mice (both males and females) that were treated subcutaneously with melatonin at a dose of 2.5 mg/mouse (80 mg/kg) twice a week for a duration of 2.5–5 months (32,66). "

So from what line of mice are you?

[Lufega]

Found this study.

Protective role of melatonin against the mercury induced oxidative stress in the rat thyroid.
Rao MV, Chhunchha B.

Department of Zoology, School of Sciences, Gujarat University, Navarangpura, Ahmedabad, Gujarat 380009, India.

Present study investigated the protective role of melatonin (MLT, 5mg/kg body wt., ip) against the long term effects of mercuric chloride (MC; 2 and 4mg/kg body wt., po) in the thyroid gland of the rats through certain antioxidative indices like superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione (GSH), catalase (CAT) and lipid peroxidation (LPO), other biochemical parameters such as succinate dehydrogenase (SDH), adenosine triphosphatase (ATPase), acid phosphatase (ACPase) and alkaline phosphatase (ALPase) were also measured. Antioxidative enzymes and other parameters showed a significant reduction while LPO and mercury levels increased significantly in a dose dependent manner in MC treated animals as compared to control groups. Co-treatment with MLT revealed no significant effect on antioxidative and metabolic indices in the thyroid gland of rats. The results of present study thus strongly suggest that mercury affected antioxidant defense system and other metabolic enzymes of thyroid. Co-administration of melatonin exerted a protective effect against mercury induced endocrine toxicity.