Role of copper complexes in the protection against stress-induced gastric ulcer in rats

ABSTRACT

Copper complexes achieve an anti-ulcer activity, several investigations were submitted to clarify the possible mode of action of these copper complexes as potent anti-ulcer drugs. These agents have a wide range of pharmacological activities that could be explained on the basis of the activation of copper dependant enzymes and their physiochemical properties. Copper complexes are reported to have potent anti-inflammatory and anti-ulcer effects. All of these copper complexes were found to be more active than either inorganic copper salts or their parent completing agents, Copper complexes were effective in reducing ulcer number as well as ulcer severity, they have an antisecretory activity. To further clarify this point, the present study was conducted to evaluate anti-ulcer activity of two types of copper complexes which are Cu [l]-[nicotinic acid][2]Cl complex and Cu[II] [glycinate][2] complexe and their combination in water immersion-restraint stressed [WIRS] ulcer rat model. The present study was conducted on 25 mule Wister albino rats, that were randomly divided info three groupsGroup I Control non-stressed group in which animals were received only an intragastric dose of 0, 5ml of vehicle [0.25% Tween -80 in saline solution]. Group II Non-pretreated WIRS group; in which rats were subjected to restraining by WIRS and received an intragastric dose of 0.5ml of vehicle. Group III Treated WIRS groups in which rats were subjected to restraining and subdivided according to the received drug into Subgroup A received an intragastric dose of 8 mg/kg body mass Cu[I]-[nicotinic acid][2]Cl complex, in 0.5ml of vehicle immediately prior to stress. Subgroup B received an intragastric dose of 5 mg/kg body mass Cu[II][glycinate]2 complex, in 0.5ml of vehicle immediately prior to stress. Subgroup C received an intragastric dose of 5 mg/kg body mass Cu[II] [glycinate][2] complex + 8 mg/kg body mass Cu[T]-[nicotinic acid][2]CI complex, in 0.5 ml of vehicle immediately prior to stress.Group II and III were subjected to restraining by fixing I he four limbs to a metal board, and placed in a water bath maintained to the level of the xiphoid process at a temperature of 23 +/- 1 °C for 3 to 5 hours.Blood samples were taken from all groups as plasma for determination of total superoxide dismutase [SOD] activity or serum for determination of total nitrite level. After withdrawal of the blood samples, their stomachs were removed and opened along the greater curvature. All the stomachs were formalin fixed and paraffin embedded, for assessment of histopathological changes affecting these structures using light microscopical examination. Administration of intragastric copper complexes increased plasma level of SOD from 0.54 +/- 0.02 unit/ml and 0.32 +/- 0.63 unit/ml for control non-stressed group and non-pretreated WIRS group to 0.84+0.10 unit/ml 1.39 +/- 0.15 unit/ml and 2.27 +/- 0.13 unit/ml for Cu[I]-[nicotinic acid][2]Cl complex, Cu[II][glycinate][2] complex and combination of two types of copper complexes, respectively. In the other hand, WIRS was associated with a significant increase in total serum nitrite level with a mean of 70.11 +/- 6.12 micro mol/1 in a comparison with non stressed group [32.09 +/- 2.05 micro mol/l]. Pretreatment of WIRS animals with both types of copper complexes; Cu[I]-[nicotinic acid][2]Cl complex and Cu[Il] [glycinate][2] complex and their combinations intragastrically did not produce a significant reduction of nitrite level, compared to WIRS group, with means 59 +/- 1.90 micro mol/L, 64.93 +/- 2.66pmol/L and 63.20+1.78 micro mol/L for both [Cu[l]-[nicotinic acid][2]Cl complex and Cu[II] [glycinate][2] complex and their combined mixture respectively. The histopathological findings of the light microscopical examination demonstrated that there was no microscopic abnormality in the gastric mucosae in the non-stressed control group [group I]. Moderate to severe gastric erosion was seen in the examined cases, with denudation of parts of the gastric mucosae of different thickness. A complete gastric ulceration with complete necrosis of parts of the gastric mucosaeseen in the most severe forms of non-pretreated WIRS group [group II]. Either no histopathologic abnormality or mild erosion was seen in WIRS groups treated with Cu[I]-[nicotinic acid][2]Cl, Cu[II][glycinate]2 complexes and their combined mixture [group III], From these results It can be concluded that both intragastrically injected copper complexes and their combined mixture exerted protective effect on the gastric mucosa of WIRS induced ulcer in rats. This is confirmed by the incosistantly measured biochemical parameters [plasma SOD and serum nitrite levels] and the histopathological examination of the gastric mucosa