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J. Duhok Univ., Vol.14, No.1 (Pure and Eng. Sciences), Pp 30-38, 2011<br />

The mechanisms were by oxidative stress plays a<br />

role in the pathogenesis of HTN involve in both<br />

hemodynamic (vasoconstrictive) and structure<br />

mechanisms (Denu et al.,1998). Vitamin E or C<br />

which they represent as antioxidants, might be<br />

strengthen the ability of melatonin to reduce<br />

further degree of blood pressure. Melatonin can<br />

significantly lower plasma ET-1(Maulood,2005),<br />

it can also reduce serum total cholesterol and<br />

serum triacylglycerol (Nishida et al.,2002).<br />

Additionally, Sozmen et al., (1998) concluded<br />

that increased total cholesterol, triacylglycerol,<br />

low-density lipoprotein (LDL) and decreased<br />

high-density lipoprotein(HDL) values were<br />

found in patients with HTN. As mentioned<br />

previously, melatonin seems to interfere with<br />

peripheral and central autonomic system with<br />

subsequent decrease in the tone of adrenergic<br />

system and an increase in cholinergic system<br />

(Paulis and Simko,2007). Unlike other<br />

antioxidant, melatonin also does not undergo<br />

redox cycling; melatonin once oxidized can not<br />

be reduced to its former state because it forms<br />

several stable end products upon reacting with<br />

free radicals (Pechanova et al., 2006).<br />

Meanwhile, melatonin, vitamin C ,vitamin E and<br />

their combinations treatments caused the same<br />

degree of SBP reduction on the eighth and tenth<br />

week. One possible hypothesis is that long term<br />

administrations of these treatments might<br />

improve the hypertensive effects of lead<br />

exposure through normalizing NO levels as<br />

detected in the current results on the last<br />

week of treatments.<br />

Current study demonstrated that long-term<br />

lead administration significantly decreased<br />

serum calcium, this result may be due to reduces<br />

in sarcolemmal calcium influx (Vassalo et<br />

al.,2008). Furthermore, different considerations<br />

have been raised to explain the pathogenesis of<br />

lead-induced HTN, such as an increased<br />

intracellular calcium concentration (Khali-<br />

Manesh et al., 1993). However, vitamin E<br />

increased serum calcium , its combination with<br />

vitamin C reduced and returned it to the Pb<br />

group. This result is consist with Norazlina et<br />

al., (2004) presented that vitamin E deficiency<br />

caused hypocalcaemia during the first month of<br />

the treatment period, increased the parathyroid<br />

hormone level in the second month and<br />

decreased the bone calcium content in the 4th<br />

lumbar bone at the end of the treatment.<br />

Interestingly, vitamin C and E in combination<br />

returned serum calcium to normal values. The<br />

reason of this result may firmly related with<br />

vitamin C rather than vitamin E. Boaz et al<br />

.,(2005) concluded that vitamin C<br />

supplementation could prevent bone loss caused<br />

by chitosan through the increment of retained<br />

Ca +2 followed by suppression of urinary<br />

Ca +2 excretion.<br />

Melatonin and its combination with vitamin<br />

E and C decreased serum potassium significantly<br />

compared with Pb group. Maulood, (2005)<br />

found that melatonin decreased ET-1, thereby<br />

decreasing serum potassium level. However the<br />

evidence for direct action of melatonin on<br />

adrenal gland is highly conflicting in nocturnal<br />

rodents like rats (Reiter et al., 2008). Hurwitz et<br />

al., (2003) demonstrated that there was a diurnal<br />

variation of aldosterone and plasma renin<br />

activity in relation to melatonin, they reported<br />

that melatonin precedes aldosterone secretion<br />

independent on plasma renin activity, in turn<br />

increase the potassium excretion.<br />

There were no significant changes in body<br />

weight among the studied groups, however, on<br />

the last week of treatments, co-administration of<br />

melatonin and vitamin E slightly reduced body<br />

weight comparing with Pb group. This finding is<br />

confirmed by Liu and Huang (1996)who<br />

showed that, rats fed the vitamin E diet had<br />

significantly lower body weight gain and food<br />

intake than rats fed the vitamin E-deficient<br />

control diet. Additionally, it has been<br />

documented that melatonin reduced plasma<br />

leptin (Nishida et al., 2002). Thus, leptin serves<br />

a primary role as an anti-obesity hormone<br />

(Ahima and Flier,2000).<br />

In conclusion, long term lead-treated rats<br />

exhibited marked elevation of blood pressure<br />

and heart rate, significant reduction of serum NO<br />

and calcium levels. These abnormalities nearly<br />

disappeared with the antioxidants melatonin in<br />

combination with vitamin E or C more than<br />

vitamin E, C and their combinations.<br />

REFERENCES<br />

-Ahima, R.S.; Flier, J. S., (2000). Leptin. Annu. Rev.<br />

Physiol. 62:413–37<br />

-Attri, J; Dhawan, V; Mahmood, S; Pandhi, P; Parwana,<br />

H.K and Nath R.(2003): Effect of vitamin C<br />

supplementation on oxidative DNA damage in an<br />

experimental model of lead-induced hypertension.<br />

Ann Nutr Metab. ;47(6):294-301.<br />

-Badavi ,M; Mehrgerdi ,F.Z; Sarkaki ,A; Naseri, M.K,and<br />

Dianat, M.(2008) Effect of grape seed extract on<br />

lead induced hypertension and heart rate in rat. Pak<br />

J Biol Sci. 15;11(6):882-7.<br />

-Boaz ,M; Weinstein ,T; Matas, Z; Green, Smetana<br />

.S(2005): Peripheral vascular disease and serum<br />

phosphorus in hemodialysis: a nested case-control<br />

study. Nephrol. 63(2):98-105.<br />

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