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اشنایی با اداب و رسوم و...یزد - مقاله شیمی
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مقاله شیمی

   نوشته شده توسط: r.z n.a    

Available online http://www.academicjournals.org/ijmms
2009 Academic Journals



Full Length Research paper

Prolonged administration of high doses of copper
nicotinate to rats: Effect on biochemical and cellular
constituents of blood and on copper level in serum,
liver and muscle

Attia H. Atta1
*, Salah Fathy2
, Gohar, M.
2
, Reem Jan3
, Gihan Kamel
1
, Samar M. Mouneir
1
and
Soad M. Nasr
4


1
Pharmacology Department, Faculty of Veterinary Medicine, Cairo University Egypt.
2
Callcure Center for Drug Research, Egypt.
3
Clinical Pathology Department, Faculty of Medicine, Cairo University, Egypt.
4
National Research Center, Giza, Egypt.

Accepted 7 April, 2009

The effect of prolonged administration of high doses of copper nicotinate on biochemical and cellular
constituents of blood and on copper level in serum, liver and muscle was studied in rats. Oral
administration of copper nicotinate at doses of 0.8 or 4.0 mg/kg body weight (b. wt.) for 6 weeks did not
affect GOT, creatinine or cholesterol in serum of rats. When given at 4.0 mg/kg b. wt. for 8 weeks copper
nicotinate significantly (P <0.05) increased GOT, GPT, urea, creatinine and cholesterol in serum of rats.
Minimal hematological changes were observed particularly when copper nicotinate was given at the
high dose for 8 weeks. After administration of copper nicotinate at a dose of 0.8 and 4.0 mg/kg b. wt.
copper level increased in the serum. The concentrat of copper in liver and muscle tissue initially
increased through the first 2 weeks, but its level decreased within the next 2 weeks and remained
almost at this level up to the 10th
week. The present data indicate the safety of copper nicotinate
complex when given at a high dose for 6-8 weeks. This was also confirmed by the high LD50 in mice
(1104.17 and 128.33 mg/kg b. wt. after oral and intraperitoneal route respectively.

Key words: Copper nicotinate, copper complex, copper high doses, copper concentration, serum biochemical
changes, hematological changes.


INTRODUCTION

Copper deficiency is extremely rare because the amount
present in food is more than adequate to provide the
needed body requirements (Velasco-Reynold et al.,
2008). Copper is required for the function of several co-
enzymes essential for different physiological functions
(Lee et al., 1976; Linder, 1991). The daily copper require-
ment for individuals of more than 11 years is estimated to
be 1.5-2.5 mg (Sandstead, 1982). However the tolerable
upper intake level of copper is ranging from 5 to 10 mg
elemental copper daily. A dose of elemental copper up to



*Corresponding author. E-mail: attaattia52@yahoo.com. Fax:
0966 63801360.
15 mg / day for an adult can be considered as a safe
supplemental dose. Above this dose some gastrointes-
tinal side effects can occur (Araya et al., 2005). As a the-
rapeutic dose, risk benefit ratio can be in favor of in-
creasing the dose if treating a serious condition. Diet can
be supplemented by copper in different forms such as
copper sulfate or tribasic copper chloride. However, re-
cently there is an increasing evidence for the use of cop-
per complexes such as copper nicotinate and 2-methyl-
thionicotinate in several clinical situations (El-Saadani et
al., 1993; Dudova et al., 2002; Song et., 2003; El-Saada-
ni, 2004; Salama et al., 2007). The effect of copper com-
plexes on the health status requires investigations. This
necessitates studying the effect of high doses of copper
nicotinate on some serum and blood parameters andAtta et al. 179



Table 1. Effect of copper nicotinate after 6 weeks of oral administration on serum biochemical constituents of rats (Mean ±
SD, n=5).

GOT I.U./l GPT I.U./l Urea mg/dl Creatinine mg/dl Cholesterol mg/dl
Control 131.0±17.1a
44.0±4.2b
18.3±1.2 b
0.6±0.1 a
59.0±4.6 a

Copper nicotinate (0.8mg/kg) 120.6±7.5 a
40.4±4.3b
16.4±1.4ab
0.5±0.2 a
56.0±6.5 a

Copper nicotinate (4.0 mg/kg) 134.0±3.8 a
52.0±4.5c
16.60±1.1b
0.6±0.3 a
55.0±7.8 a


Means of different asterisks are significantly different at P < 0.05.




estimating copper level in serum, liver and muscles of
rats. Moreover the acute LD50 was determined in mice.


MATERIALS AND METHODS


 
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