Treatment Of Oxidative Stress-mediated Diseases Research Articles

Protective effects of methanolic extract of Andrographis paniculata (Burm.f.) Nees leaves against arsenic-induced damage in rats

BackgroundMedicinal plants are natural sources of antioxidants effective in the treatment of oxidative stress-mediated diseases. This study aims to evaluate the hepato-renal protective efficacy of Andrographis paniculata leaves methanolic extract in arsenic-induced oxidative stress. Animals were divided into four groups of six animals per group. The rats in groups 1 and 2 received normal saline, while rats in groups 3 and 4 received 200 mg/kg body weight of A. paniculata or ascorbic acid per day, respectively, for 7 days orally. The rats in groups 2, 3, and 4 received a single dose of arsenic at 10 mg/kg body weight intraperitoneally on day 7, and 24 h later, rats in all the groups were killed and the blood, liver, and kidney samples were collected for biochemical/histological studies.ResultsAdministration of arsenic to rats induced a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, urea, creatinine, and triglycerides in the plasma, while it decreased superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) activities in the liver and kidney. It also significantly reduced the levels of white blood cells (WBC), red blood cells (RBC), platelet (PLT), and lymphocytes (LYM) in the blood. However, the levels of AST, ALT, cholesterol, urea, creatinine, and triglycerides in the plasma of groups of rats that received A. paniculata extract before administration of arsenic were decreased, while their SOD, GSH, and CAT levels were elevated in the liver and kidney. The values of their WBC, RBC, PLT, and LYM were also significantly increased when compared to the arsenic group rats. Histological observations showed varying degrees of liver damage in the arsenic group rats, while the histoarchitecture of the liver of rats that received A. paniculata extract were significantly improved.ConclusionsThis study demonstrated that A. paniculata extract ameliorates arsenic-induced hepato-renal toxicity and could be exploited in the management of toxicity effects associated with the arsenic.

Schisandrin A prevents oxidative stress-induced DNA damage and apoptosis by attenuating ROS generation in C2C12 cells

The generation of excessive reactive oxygen species (ROS) by oxidative stress has various deleterious effects on cellular constituents. Therefore, the discovery of natural products that can inhibit the production of ROS may be effective in suppressing the onset and treatment of oxidative stress-mediated diseases. Despite the antioxidant efficacy studies on various substances in the genus Schisandra used as traditional medicine, research on the efficacy of schisandrin A, a class of active lignans, remains insufficient. This study was conducted to evaluate the protective effect of schisandrin A on DNA damage and apoptosis induced by hydrogen peroxide (H2O2) in C2C12 cells. Results showed that schisandrin A effectively attenuated H2O2-induced cytotoxicity and DNA damage, which was related to the blockage of ROS accumulation. Schisandrin A also prevented the decrease in ATP content by H2O2 and restored the H2O2-induced activation of AMP-activated protein kinase. In addition, schisandrin A prevented the release of H2O2-induced cytochrome c into the cytoplasm presumably by inhibiting the loss of mitochondrial membrane potential and the changes in the Bcl-2 family protein expression by H2O2. Furthermore, the blocking of H2O2-induced apoptosis by schisandrin A was associated with the inhibition of poly (ADP-ribose) polymerase degradation by the inactivation of caspase-3. These results suggest that schisandrin A maintains energy metabolism through the preservation of mitochondrial function while eliminating ROS generated by H2O2 in C2C12 cells. Therefore, our data indicate that schisandrin A may have a beneficial effect on the prevention and treatment of diseases associated with apoptosis induced by oxidative stress.

Hesperidin Protects Renal and Hepatic Tissues Against Free Radical-Mediated Oxidative Stress During DMBA-Induced Experimental Breast Cancer

Hesperidin has been reported to have an excellent and wide variety of biological activities. This property has brought the compound to a new stage in the treatment of various oxidative stress-mediated diseases. The present investigation was aimed to evaluate the therapeutic potential of hesperidin by assaying the activities of antioxidant enzymes, lipid peroxidation, membrane bound marker enzymes, adenosine triphosphates, and TCA cycle enzymes, especially in kidney tissues during 7,12-dimethybenz(a)anthracene-induced breast cancer. Daily oral administration of hesperidin (30 mg/kg body wt) to breast cancer-bearing rats for 45 days demonstrated a significant (P < .05) decline in renal lipid peroxidation and membrane bound marker enzymes, as well as a remarkable increase in adenosine triphosphatases, mitochondrial functional enzymes, and renal antioxidants. Furthermore, histological studies of liver and kidney provided evidence of biochemical alterations. Thus, the protective effects of hesperidin on attenuating the peroxidation reaction and membrane bound marker enzyme activities as well as upregulation of adenosine triphosphatases, TCA cycle enzymes, and antioxidants suggest promising uses of flavonoglycoside hesperidin in the future treatment of oxidative stress-mediated diseases.

Enhanced antioxidant and cytoprotective abilities of vitamin E succinate is associated with a rapid uptake advantage in rat hepatocytes and mitochondria

Numerous in vitro studies attest to the enhanced ability of vitamin E succinate (TS), as compared with conventional vitamin E compounds such as unesterified d-α-tocopherol (T) and d-α-tocopheryl acetate (TA), to protect hepatocytes from toxic oxidative stress. In the present study we tested the hypothesis that this unique protective ability is related to an enhanced cellular accumulation of TS. The results of this study indicate, using both in vitro and in vivo model systems, that acute TS administration results in a rapid increase in T and TS content and antioxidant protection of hepatocytes and mitochondria. In contrast, conventional vitamin E compounds such as T and TA lack these same protective properties. We suggest that TS acts as a unique delivery system for T, rapidly accumulating in cellular and mitochondrial membranes and gradually releasing active T to prevent membrane oxidative damage. We propose that TS administration may prove useful for the prevention and treatment of oxidative stress-mediated diseases, especially those of mitochondrial origin.