Liposomal Curcumin Attenuates the Incidence of Oxidative Stress, Inflammation, and DNA Damage Induced by Copper Sulfate in Rat Liver.

BACKGROUND: Copper is an essential element that is used widely in agriculture as fungicides and insecticides; for example, it is used to control schistosomiasis and as an antiseptic and germicide. Copper sulfate (CuSO4) induces multiorgan dysfunction through the stimulation of reactive oxygen species and oxidative stress. Despite the numerous pharmacological effects of curcumin (CUR), its pharmacokinetic properties are less promising. Hence, there is an urgent need for novel, effective strategies to attenuate heavy metal toxicity and consequently improve the treatment efficiency. Liposomal curcumin (L-CUR) improves the dissolution, stability, and bioavailability of treatment agents. This study compared the efficacy of CUR and L-CUR with that of desferrioxamine (DES), which is a heavy metal chelator against CuSO4 hepatotoxicity. METHODS: All treatments with the aforementioned antioxidants were administered for 7 days along with CuSO4. Serum levels of alanine aminotransferase, aspartate transaminase, lactate dehydrogenase, and C-reactive protein, hepatic nitric oxide (NO), and lipid peroxides (malondialdehyde) were measured; protein expression of cyclooxygenase 2 and DNA fragmentation were evaluated. Histopathological examinations were also conducted. RESULTS: A toxic dose of CuSO4 induced elevations in the previously measured parameters; these increases were reduced by the tested antioxidants, whereas glutathione (GSH) and superoxide dismutase (SOD) levels were decreased. Treatment with the antioxidants in question modulated these levels. Liposomal CUR has more hepatoprotective efficiency than CUR, and its efficacy was similar to that of DES. The histopathological examinations confirmed these results. CONCLUSIONS: Liposomal CUR may be useful for the prevention of CuSO4-induced liver injury. Cyclooxygenase 2 protein expression and DNA fragmentation were involved in CuSO4 toxicity and treatment.

Prophylactic Administration of Nanocurcumin Abates the Incidence of Liver Toxicity Induced by an Overdose of Copper Sulfate: Role of CYP4502E1, NF-κB and Bax Expressions.

BACKGROUND: The consequences of excess copper in human tissue are the alterations in the oxidative stress markers and peroxidative damage of membrane lipids. Unselective copper binding may be the clue to damaging impact to protein construction and hence modifying their biological functions. The aim of this study is to match the hepatoprotective efficacy of curcumin (CM) or nanocurcumin (NCM) with that of desferrioxamine (DSF; standard heavy metal chelator) against toxic doses of copper sulphate (CuSO4). METHOD: All treatments were given simultaneously with CuSO4 for 7 days. RESULT: CuSO4 administration elevated serum alanine transaminase, and hepatic nitric oxide (NO), lipid peroxide, and caspase-3 as well as protein expression of cytochrome P4502E1, and nuclear factor-κB (NF-κB) and Bax gene expressions. On the other hand, hepatic levels of reduced glutathione, superoxide dismutase, and interleukin-10 were decreased, whereas DNA degradation was increased as well compared with the control group. The administration of the aforementioned antioxidants ameliorated all the previous altered measured parameters. Interestingly, NCM achieved the most pronounced hepatoprotective effect nearly equivalent to that of DSF. CONCLUSION: It was concluded that NCM is considered a promising candidate against CuSO4 toxicity, and cytochrome P450, NF-κB, and Bax are involved in its toxicity and treatment.