Diminution of Hepatic Response to 7, 12-dimethylbenz(α)anthracene by Ethyl Acetate Fraction of Acacia catechu Willd. through Modulation of Xenobiotic and Anti-Oxidative Enzymes in Rats

Abstract

BackgroundLiver is the primary metabolizing site of body and is prone to damage by exogenous as well as endogenous intoxicants. Polycyclic aromatic hydrocarbons such as 7, 12- dimethylbenz(α)anthracene (DMBA) is an exogenous hepatotoxin, which is well known for modulating phase I, II and anti-oxidative enzymes of liver. Plants contain plethora of polyphenolic compounds which can reverse the damaging effect of various xenobiotics. The present study investigated protective role of the ethyl acetate fraction of Acacia catechu Willd. (EAF) against DMBA induced alteration in hepatic metabolizing and anti-oxidative enzymes in rats.Methodology and Principal FindingsThe rats were subjected to hepatic damage by treating with DMBA for 7 weeks on alternative days and treatment schedule was terminated at the end of 14 weeks. The rats were euthanized at the end of protocol and livers were homogenized. The liver homogenates were used to analyse phase I (NADPH-cytochrome P450 reducatse, NADH-cytochrome b5 reductase, cytochrome P420, cytochrome b5), phase II (glutathione-S-transferase, DT diaphorase and γ-Glutamyl transpeptidase) and antioxidative enzymes (catalase, superoxide dismutase, ascorbate peroxidase, glutathione reductase, guiacol peroxidase and lactate dehydrogenase). Furthermore, other oxidative stress parameters (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes and reduced glutathione) and liver marker enzymes (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and alkaline phosphatase) were also studied. The DMBA induced significant changes in activity of hepatic enzymes that was reversed by treatment with three dose levels of EAF.ConclusionIt is concluded that EAF affords hepato-protection against DMBA in rats through modulation of phase I, II and anti-oxidative enzymes.

Protective and Curative Effects of the Sea CucumberHolothuria atraExtract against DMBA-Induced Hepatorenal Diseases in Rats

“…Polycyclic aromatic hydrocarbons, such as 7,12-dimethylbenz[a]anthracene (DMBA), are environmental pollutants that exert multiple toxic and carcinogenic effects [ 4 ]. DMBA is an exogenous hepatotoxin, which is well known for modulating phases I and II and antioxidative enzymes of liver [ 5 ]. DMBA is a major breast cancer risk [ 6 ].…”

“…DMBA is a major breast cancer risk [ 6 ]. Excessive reactive oxygen species (ROS) are also generated during metabolic activation of DMBA [ 5 ]. Emerging evidences suggest that DMBA induces the production of ROS that result in lipid peroxidation, DNA damage, and depletion of cell antioxidant defense systems [ 5 , 7 ].…”

Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model

“…27 Many studies recorded that patients with leukemia have higher levels of MDA 28 and a decrease in GSH level following carcinogen (DMBA) administration; which may be due to the utilization of antioxidants to scavenge the free radicals. 29 Malignant proliferation of leukemic cells is supported by a cytokine produced partially by the leukemic cells themselves. 30 Some of these are produced and secreted by the leukemic cells themselves.…”

Bioprotective efficacy of erucin against 7,12-dimethylbenz(α)anthracene-induced microstructural changes in male wistar rats

“…the xenobiotic compounds are metabolized by liver but other organs such as the lungs, stomach and kidneys play a key role in their metabolism and excretion (12)(13)(14). these xenobiotic compounds are countered efficiently by plant secondary metabolites such as isothiocyanates (15). Among the various isothiocyanates, erucin (an analogue of sulforaphane) has been isolated and evaluated for its ability to protect the rats against the toxic effect of DMBA.…”