Search

Owing to their structure and function, low-density lipoproteins (LDLs) are particularly susceptible to the oxidative modifications. To prevent against oxidative modification of LDL, L-carnitine, with endogenous small water-soluble quaternary amine possessing antioxidative properties, was used. The aim of this paper was to prove the in vitro influence of L-carnitine on the degree of oxidative modification of the lipid part (estimated by conjugated dienes, lipid hydroperoxides, and malondialdehyde levels) and the protein part (estimated by dityrosine and tryptophan levels) of LDL native and oxidized by cooper ions. The level of lipophylic LDL antioxidant—α-tocopherol was also measured. Oxidation of LDL by Cu2+ enhanced lipid peroxidation. That was manifested by a statistically significant increase in the content of malondialdehyde (threefold), conjugated dienes (up to about 30%), and lipid hydroperoxides (up to about 50%). Cu2+ ions were also the cause of oxidative modifications of the protein part of LDLs. It was manifested by a significant increase in dityrosine (by about 50%), whereas the level of tryptophan was significantly decreased threefold in relation to native LDL. Incubation of LDL with Cu2+ ions also caused a significant sixfold decrease of α-tocopherol content in oxidized LDL. However, L-carnitine caused a decrease in the level of conjugated dienes, lipid hydroperoxide, malondialdehyde, and dityrosine by about 20% to 30%, and a significant increase (by about 50%) in the content of tryptophan in comparison with oxidative LDL and in a smaller degree significant changes with native LDL. Additionally, L-carnitine caused a significant twofold increase in α-tocopherol content in oxidized LDL. The above results indicate that L-carnitine protects the lipid as well as protein part of LDL particles against oxidative modifications, and this natural antioxidant might be used to prevent against diseases of oxidative origin. [ABSTRACT FROM AUTHOR]

Antineoplastic drugs and/or their metabolites are very reactive chemically and easily react with cell components, both those neoplastic and healthy, which leads to uncontrolled cell damage. Research is being carried out to discover new drugs preventing those destructive changes in healthy cells. Amifostine is one of the few drugs with protective abilities in regard to healthy tissues during antineoplastic therapy. Amifostine alone is inactive chemically, but active metabolite amifostine WR-1065 has been assumed to protect the healthy tissues during antineoplastic therapy by bounding of anticancer drug, causing their detoxification and/or eliminating the free radicals generated during radiation and cytostatic therapy. WR-1065 also protects the healthy tissues by inhibition of apoptosis caused by irradiation and/or alkylating compounds. However, the protective mechanism of amifostine influence on healthy cells has not been fully comprehended, and the research is still being carried out. [ABSTRACT FROM AUTHOR]

Cyclophosphamide, an alkylating compound used in chemotheraphy, is metabolized into active metabolites that form reactive oxygen species. Reactive oxygen species can modify the components of both healthy and neoplastic cells in circumstances of decreased antioxidative abilities. That leads to the dysfunction of organs, including the kidneys. Therefore, drugs like amifostine, which protect healthy cells against reactive oxygen species, may be applied during cyclophosphamide therapy. The aim of this study was to evaluate the influence of amifostine on the antioxidative system of the kidneys of rats that were exposed to cyclophosphamide. Intraperitoneal administration of cyclophosphamide was found to decrease the activity of the kidney's antioxidative enzymes, such as superoxide dismutase, glutathione peroxidase, gluthatione reductase, and catalase. Amifostine, however, caused an increase in the activity of these enzymes. The administration of amifostine with cyclophosphamide partially prevented changes in the activities of the examined enzymes observed after cyclophosphamide injection. Cyclophosphamide also evoked a decrease in the levels of nonenzymatic antioxidants, such as reduced gluthatione, vitamin C, and vitamin E as well as the total antioxidant status. The administration of amifostine together with cyclophosphamide prevented changes in the concentration of evaluated nonenzymatic antioxidative parameters, increasing values of their concentration to the values in the control group. Changes in the kidneys' antioxidative abilities during detoxification from cyclophosphamide were accompanied by intensified lipid peroxidation, which was manifested by an increase in the concentration of malondialdehyde and 4-hydroxynonenal. Amifostine caused the inhibition of lipid peroxidation in the kidneys of control and cyclophosphamide-treated rats. In conclusion, our results suggest that amifostine significantly protects kidney antioxidant parameters from changes caused by cyclophosphamide treatment and, in consequence, prevents oxidative stress and phospholipid peroxidative damage. Thus, amifostine prevents renal injury and dysfunction. [ABSTRACT FROM AUTHOR]