الفهرس 
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Abstract
Drug-induced liver and kidney injury is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. Because of the significant patient morbidity and mortality associated with drug induced organ injury, the U.S. Food and Drug Administration (FDA) has removed several drugs from the market (Elgayyar et al., 2001).
Cyclosporine A (CsA) has been widely used for the prophylaxis and treatment of graft rejection in almost all types of organ transplantations in addition it is used in the treatment of wide spectrum of autoimmune diseases. However CsA has very dangerous side effects including renal, hepatic, cardiac and neural toxicity, among which, hepatotoxicity and nephrotoxicity have been most often reported as complications of cyclosporine (Elrod et al., 2010). The exact mechanism of CsA-induced hepatotoxicity and nephrotoxicity is not completely understood but, numerous experimental findings suggest that oxidative stress mechanism playing an important role in its pathology. CsA therapy induces overproduction of reactive oxygen species (ROS) in hepatocytes and lowers their antioxidant capacity (Olyaei et al., 2001).
Based on this fact, we hypothesis that oregano oil which is a natural antioxidant product without or with least possible complications can be used as an additive therapy with CsA to overcome the major side effect associated with it especially hepatotoxicity and nephrotoxicity.
In the present study, we evaluated the protective and therapeutic effects of oregano oil on liver and kidney in CsA- induced hepatotoxicity and nephrotoxicity in rats. To detect the safety of oregano oil on liver and renal functions and its effect on the oxidative stress state, we gave the oil alone to rats and the liver and renal function tests as well as oxidative stress parameter and antioxidant enzyme were evaluated. Our results revealed that, the serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin (total & direct), total protein and albumin as a liver function tests and serum level of urea and creatinine as a renal function tests in addition to, serum level of both malondialdehyde (MDA) and superoxide dismutase (SOD) were not affected by the i.p ad-ministration of 1mg/kg of oregano oil in rats for 21 days compared to control group suggesting a safe use of this oil on liver and kidney.
By measuring different biochemical parameters our results clearly demonstrated that CsA succeeded to produce hepatotoxicity and ne-phrotoxicity. Treatment of rats with CsA 30 mg/kg/day i.p. for 21 days produced highly significant increase in the serum levels of AST, ALT, direct bilirubin and urea, significant increase in the serum level of total bilirubin and creatinine, as well as significant decrease in serum levels of total protein and albumin compared to control group. Moreover, there is highly significant increase in the serum levels of both MDA and SOD compared to control group; supporting that the toxicity is mediated mostly by generation of reactive oxygen species and lipid peroxidation.
The present study demonstrated that, oregano oil and its phenolic compounds induce potent hepatorenoprotective effect against CsA in-duced toxicity in rats. This indicated as,the concomitant administration of oregano oil (1 mg/kg/day i.p.) with CsA (30 mg/kg/day i.p.) for 21 days produced highly significant reduction in the serum levels of AST, ALT, bilirubin (total & direct), urea and creatinine and significant increase in the serum levels of total protein compared to CsA treated group. Also, oregano oil with high amount of flavonoids and phenolic compounds induces potent antioxidant effects against CsA intoxication by highly significant reduction in the serum level of MDA and enhancement of the activity of the antioxidant enzyme, SOD.
However, oregano oil has no role as therapeutic agent in treatment of established hepatic and renal impairment. This indicated as the treatment of rats with CsA 30mg/kg/day i.p. followed by oregano oil1mg/kg/day i.p. for another 21 days, failed to return serum levels of liver function tests (except AST and ALT serum levels) and renal function tests to its original level compared to CsA treated group. Also, similar results obtained on oxidative stress induced by CsA. As the correction of increased MDA level and decreased SOD activity were not produced in the group which was post-treated with oregano oil after CsA intoxication compared to CsA group.