Betulinic acid protects againstN-nitrosodimethylamine-induced redox imbalance in testes of rats (original) (raw)
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Free Radicals and Antioxidants, 2013
Aim: This study investigates the reactive oxygen species detoxification potentials of polyphenolic extract of Blighia sapida arilli in the liver of N-nitrosodiethylamine-treated rats. Methods: Male rats, weighing 158 AE 2.9 g were completely randomized into 7 groups (AeG) of five rats each. Rats in C, D, E and F were administered orally once daily at 24 h interval for 7 days with 1000, 250, 500 and 1000 mg/kg body weight of polyphenolic extract of B. sapida arilli respectively. Group G was given 100 mg/kg body weight of vitamin C. On the sixth day, group B, D, E, F and G were administered with 100 mg/kg body weight N-nitrosodiethylamine (NDEA). Group A, which served as the control was treated like the test groups except, that the animals received distilled water only. Results: Reactive oxygen species detoxifying enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase) activities were significantly (P < 0.05) induced by B. sapida arilli. These inductions significantly (P < 0.05) attenuated the decrease in reactive oxygen species detoxifying enzymes mediated by NDEA treatment and compared favourably with vitamin C. NDEA-mediated elevation in the concentrations of oxidative stress biomarkers; malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and percentage DNA fragmentation were significantly (P < 0.05) lowered by polyphenolic extract of B. sapida arilli. Conclusion: Overall, the results obtained from this study revealed that the polyphenolic extract from B. sapida arilli enhanced the detoxification of reactive oxygen species in NDEA-treated rats. The polyphenols also prevented the peroxidation of lipid, oxidation of proteins as well as fragmentation of DNA component in the liver of rats and hence gave the evidence of possible prophylactic potentials of B. sapida arilli.
The aim of this study is to review a procarcinogen, the N-Nitrosodimethylamine (NDMA), liver and kidney functional enzymes (in assessing action of toxicants such as NDMA) as well as oxidative stress parameters (in assessing the extent of free radical damage and scavenging). Catalase and hydro peroxidase enzymes convert hydrogen peroxide and hydro peroxides to non-radical forms and functions as natural antioxidant in human body. Enzymes like Superoxide Dismutase (SOD) and Catalase (CAT) and compounds such as tocopherol and ascorbic acid can protect organisms against free radical damage. Lipid peroxidation is a mechanism generally recognized as being the most important in the pathogenesis of liver injury by a number of toxic compounds including NDMA.
Nutrition Journal, 2015
Remarkable interest has risen in the idea that oxidative/nitrosative stress is mediated in the etiology of numerous human diseases. Oxidative/Nitrosative stress is the result of an disequilibrium in oxidant/antioxidant which reveals from continuous increase of Reactive Oxygen and Reactive Nitrogen Species production. The aim of this review is to emphasize with current information the importance of antioxidants which play the role in cellular responce against oxidative/nitrosative stress, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue. Products of lipid peroxidation have commonly been used as biomarkers of oxidative/nitrosative stress damage. Lipid peroxidation generates a variety of relatively stable decomposition end products, mainly α, β-unsaturated reactive aldehydes, such as malondialdehyde, 4-hydroxy-2-nonenal, 2-propenal (acrolein) and isoprostanes, which can be measured in plasma and urine as an indirect index of oxidative/nitrosative stress. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative/nitrosative stress or its consequences. They may act from directly scavenging free radicals to increasing antioxidative defences. Antioxidant deficiencies can develop as a result of decreased antioxidant intake, synthesis of endogenous enzymes or increased antioxidant utilization. Antioxidant supplementation has become an increasingly popular practice to maintain optimal body function. However, antoxidants exhibit pro-oxidant activity depending on the specific set of conditions. Of particular importance are their dosage and redox conditions in the cell.
Nigerian Journal of Biochemistry and Molecular Biology, 2022
Testicular toxicity is a prime threat to male reproductive health. Humans are constantly exposed to Bisphenol A (BPA) via oral route, thus inducing reproductive toxicity. Cucumeropsis mannii seed oil (CMSO) has nutraceuticals with antioxidant potential. This present study investigated the potential of CMSO to mitigate testicular oxidative damages induced by exposure to BPA. Thirty-six (36) male Wistar albino rats, 2-3 months old, were randomly assigned into six (6) study groups; 3 control groups (CG1, CG2, and CG3) and 3 test groups (TG1, TG2, and TG3), respectively. CG1 rats received 1 ml of olive oil. CG2 rats received 100 mg/kg body weight of BPA. CG3 rats received 7.5 ml/Kg body weight of CMSO. TG1 rats were co-administered 100 mg/kg body weight of BPA and 7.5 ml/kg bodyweight of CMSO. TG2 rats were co-administered with 100 mg/kg body weight of BPA and 5 ml/kg body weight of CMSO. TG3 rats were co-administered with 100 mg/kg body weight of BPA and 2.5 ml/kg body weight of CMSO. After the trial, the rats' testes were extracted and taken for biochemical analysis. The result showed that the exposure of rats to BPA significantly (p < 0.05) increased the levels of ROS and MDA but considerably decreased the levels of GSH, CAT, SOD, GPx, IL-1β, IL-6, TNF-α, NF-ĸB, and Caspase-3 activity in the testicular homogenate. However, co-administration of BPA with CMSO significantly (p < 0.05) reversed all the dysregulations. This study reported that CMSO is a potential nutraceutical for mitigation of BPA-induced testicular oxidative damages.
Journal of Biochemical and Molecular Toxicology, 2008
The present study investigated the protective effect of gossypol, selenium, zinc, or glutathione (GSH) against dimethylnitrosamine (DMN)-induced hepatotoxicity in the livers of male mice. The expression and the activity of glutathione S-transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as well as the activity of glutathione reductase were determined after the treatment of mice for seven consecutive days with low or high doses of gossypol, selenium, zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2 h after the repeated dose treatments of mice for seven consecutive days with each antioxidant. DMN reduced the expression and inhibited the activity of GST. However, repeated treatments of mice with lowdose gossypol or high dose of either selenium or GSH followed by a single dose of DMN induced the expression and the activity of GST. In contrast, low-dose treatments of mice with zinc, selenium, or GSH followed by a single dose of DMN reduced the expression and the activity of GST compared to either control or DMN-treated groups. In addition, high-dose treatment with either gossypol or selenium markedly induced the levels of GSH compared to either control or DMN-treated groups. Interestingly, pretreatment of mice with high dose of either gossypol or selenium for seven consecutive days followed by a single dose of DMN decreased the levels of MDA, whereas DMN induced such levels. It is concluded that high dose of either gossypol or selenium is a stronger protector than zinc and GSH in ameliorating the toxic effects of DMN.
Journal of Natural Sciences Research, 2018
Atrazine (ATZ) is a selective pre-and post-emergentherbicide for combatingweeds, which however causes endocrine disruption and delays or changes in pubertal development in experimental animals. Since a paucity of information on the effects of Betulinic acid (BA), a triterpene antioxidant on ATZ toxicity was noted in literature, the present work was designed to study the effects of BA on the antioxidant profile and histopathology of liver and testes of rats treated with ATZ. The ATZ significantly increased protein levels in serum (46.2%) and liver (94.8%), while that of testes (55.9%) was significantly decreased, relative to controls. Pretreatment with BA ameliorated the effect in serum and liver compared with ATZ group. The ATZ treatment significantly lowered Superoxide dismutase (SOD) activities by 52.8% and 89.3%, and Catalase (CAT) activities by 56.9% and 53.6% in liver and testes, respectively, relative to controls, whereas the activities were significantly elevated on BA pre treatment. Malondialdehyde (MDA) was elevated by 84.65 and 85.8%, while reduced glutathione (GSH) was decreased by 51.2% and 64.2% in liver and testes, respectively when compared with controls. However, BA ameliorated the effect compared with ATZ group. In the ATZ-treated rats, liver was noted to develop mild hepatocyte degeneration and periportal cell infiltration, while foci tubular distortion and capsular congestion were observed in the testicular tissue, effects which BA pretreatment was able to ameliorate. In conclusion, Betulinic acid improved the antioxidative status of hepatic and testicular tissues against Atrazine intoxication in rats.
Does ADMA effect the oxidant/antioxidant balance in rats?
TURKISH JOURNAL OF MEDICAL SCIENCES, 2013
Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide synthase (NOS). Oxidative stress might be defined as an imbalance between protein oxidation and antioxidants. Our aim was to determine in vivo whether ADMA causes oxidative damage. Materials and methods: Thirty rats were divided into 3 equal groups: a control group, a group administered 1 mg/kg ADMA, and a group administered 2 mg/kg ADMA. ADMA was administered intraperitoneally for 7 days. Malondialdehyde (MDA), protein carbonyl (PC) content, and nitrate+nitrite concentrations were measured with serum samples. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities were analyzed with plasma samples. Results: A significant increase in MDA concentration was observed in the ADMA groups, but this increase was not dose-dependent. However, no significant changes in PC content or nitrate+nitrite concentration were observed. Furthermore, catalase, SOD, and GSH-Px activity was suppressed in the ADMA groups. Suppression of GSH-Px activity was dose-dependent. Conclusion: ADMA results in oxidative damage in vivo with lower doses than in NOS inhibition. ADMA has more of an oxidative effect on lipids than it does on proteins. Antioxidant enzymes must be consumed in significant amounts to remove the stress produced by ADMA.
Toxicology Letters, 2009
Arsenic (As) is a well known toxicity inducer. Recent investigations, however, showed that it might have some therapeutic application in cancer treatment. These dual roles of arsenic have attracted a renewed research in organ pathophysiology. In this study, we report that As administration (in the form of NaAsO 2 at a dose of 10 mg/kg body weight for 2 days, orally) induces apoptosis in testicular tissue of the experimental rats by the activation of caspase-3 and reciprocal regulation of Bcl-2/Bad with the concomitant reduction of mitochondrial membrane potential and increased level of cytosolic cytochrome C. Arsenite has also been shown to induce activation of mitogen-activated protein kinases (MAPKs), Akt as well as NF-B (p65) in testicular tissue. In addition, As significantly decreased testicular 5-3-HSD and 17-HSD activities and reduced the plasma testosterone level, testicular sperm count and sperm motility. Besides, arsenite exposure increased the levels of reactive oxygen species (ROS), serum TNF-␣, As accumulation and lipid peroxidation and decreased the activities of the antioxidant enzymes and glutathione in the testicular tissue. Oral administration of taurine (at a dose of 100 mg/kg body weight for 5 days) was found to be effective in counteracting As-induced oxidative stress, attenuation of testicular damages and amelioration of apoptosis in testicular tissue by controlling the reciprocal regulation of Bcl-2/Bad, phospho-ERK1/2, phospho-p38, phospho-Akt and NF-B. Taurine was also found to play similar beneficial role via mitochondrial dependent pathways in As-induced testicular damages leading to apoptotic cell death.
Reproductive Toxicology, 2002
Utilization of highly enriched preparations of steroidogenic Leydig cells has proven invaluable for studying the direct effects of various hormones and agents on Leydig cell function in vitro. It is widely reported that male reproductive organs are particularly susceptible to the deleterious effects of reactive oxygen species (ROS) and lipid peroxidation, which ultimately lead to impaired fertility. The purpose of the study was to examine the potential of 2-bromopropane (2-BP) to induce oxidative stress and antioxidant function in primary cultures of rat Leydig cells. Leydig cells were isolated from the testes of Sprague-Dawley rats. The purity of Leydig cells was determined to be 94.6% and the cells maintained their testosterone secreting capabilities for 48 h. Fresh medium containing 2-BP (1.00, 0.10, 0.01 mM, and vehicle control) and 1 U human chorionic gonadotropin (hCG) were added in the cell culture. Superoxide dismutase (SOD) activity, malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) were analyzed in the medium of each well by biochemical methods. Additionally, DNA damage was examined using the Comet assay. The proportion of cells with undamaged DNA was decreased significantly and those with different grades of damaged DNA were increased significantly in the cells exposed to 2-BP. The level of MDA and GSH-PX activity increased significantly in the cell groups exposed to 0.10 and 1.00 mM 2-BP, whereas, SOD activity decreased considerably in these two groups of cells when compared to the control. The data indicate that 2-BP induces DNA damage, impairs functional antioxidant cellular defenses, and enhances the lipid peroxidation in cultured Leydig cells. These effects may be responsible for the testicular toxicity noted in laboratory animals and humans.
Journal of Biological Chemistry, 1996
Transcription factors AP-1 and NF-B have been implicated in the inducible expression of a variety of genes in response to oxidative stress. Recently, based on the observation that butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC) induce AP-1 binding activity and AP-1-dependent gene expression and assuming that these compounds exert an antioxidant effect, it was claimed that AP-1 is an antioxidant-responsive factor. To determine whether AP-1 can be responsive to both oxidant and antioxidant, we examined the nature of BHA and PDTC inducing activity. Using EPR spectroscopy to detect semiquinone radicals, we demonstrate the autoxidation of BHA metabolite tert-butylhydroquinone (TBHQ) to tert-butylquinone.