GST), Glutathione Reductase Research Articles

Aucubin mitigates nonylphenol-induced renal damage by attenuating apoptosis, oxidative stress and histopathological profile

Nonylphenol (NP) is potent noxious pollutant which is documented to induce nephrotoxicity via escalating the levels of oxidative stress in renal tissues. Aucubin (AUC) is a novel phytochemical having tremendous pharmacological abilities. This research aimed to estimate the efficacy of AUC against NP intoxicated renal impairment in male albino rats. 48 albino rats were randomly assigned into four different groups viz. control group, NP administered group (50 mg/kg), NP + AUC administrated (50 mg/kg + 40 mg/kg) group and AUC treated (40 mg/kg) group. Our results showed that NP intoxication raised urinary proteins, creatinine, urea, urobilinogen, NGAL and KIM-1 levels. Besides, NP exposure lowered the levels of creatinine clearance and albumin. Furthermore, NP treatment lowered level of total protein, activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GSR) & glutathione (GSH) contents along with the level of total antioxidant status (TAS) however, raising the oxidative stress markers levels Thiobarbituric acid reactive substance (TBARS), reactive oxygen species (ROS), hydrogen peroxide (H2O2) & total oxidant status (TOS). Additionally, following the NP administration, the levels of Bax, caspase-9, & caspase-3 were augmented however the Bcl-2 level was decreased. Furthermore, rats exposed to NP showed various histopathological disruptions. Whereas treatment with AUC showed a palliative effect against NP-induced renal damage, restoring all alterations to normal levels. Taken together, AUC administration convalesced NP-induced kidney impairment.

Antioxidant Defense Enzymes in Multiple Sclerosis: A 5-Year Follow-up Study.

Oxidative stress biomarkers are increased in multiple sclerosis (MS) lesions. Antioxidant defense enzymes regulate reactive oxygen species that can cause tissue injury in MS. The study of 91 subjects included 64 relapsing-remitting MS (RR-MS, 72% female, baseline age 44.6±SD 11 years; disease duration: 13.3±8.8 years; median EDSS 2.0, IQR: 1.8) and 27 healthy controls (HC) subjects at baseline and 5-year follow-up (5YFU). Serum glutathione peroxidase (GPX), glutathione S-transferase (GST), glutathione reductase (GSHR), superoxide dismutase (SOD), and paraoxonase-1 (PON1) arylesterase and paraoxonase activities were measured using kinetic enzyme assays. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and an apolipoprotein (Apo) panel with ApoA-I, ApoA-II, ApoB, ApoC-II and ApoE were obtained. Serum neurofilament (sNfL) was used to assess axonal injury. Disability was measured on the Expanded Disability Status Scale (EDSS). GSHR activity was lower in HC compared to RR-MS at baseline and 5YFU. GPX (p=0.008) and PON-1 arylesterase and paraoxonase activities (both p=0.05) increased between baseline and 5YFU in HC but did not increase in RR-MS. At baseline and 5YFU, GPX and GST were associated with TC, LDL-C, and ApoA-II; GSHR was associated with ApoA-II and ApoC-II. Antioxidant enzymes were not associated with sNfL or EDSS in RR-MS. RR-MS patients did not exhibit the changes in antioxidant enzyme activities over 5YFU found in HC; however, the differences were modest. Antioxidant enzyme activities are not associated with disability.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats.

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Protective effect of Launaea procumbens (L.) on lungs against CCl4-induced pulmonary damages in rat.

BackgroundLaunaea procumbens (L.) is traditionally used in the treatment of various human ailments including pulmonary damages. The present study was arranged to evaluate the role of Launaea procumbens methanol extract (LME) against carbon tetrachloride (CCl4) induced oxidative pulmonary damages in rat.Methods36 Sprague–Dawley male rats (170-180 g) were randomly divided into 06 groups. After a week of acclamization, group I was remained untreated while group II was given olive oil intraperitoneally (i.p.) and dimethyl sulfoxide (DMSO) orally, groups III, IV, V and VI were administered CCl4, 3 ml/kg body weight (30% in olive oil i.p.). Groups IV, V were treated with 100 mg/kg, 200 mg/kg of LME whereas group VI was administered with 50 mg/kg body weight of rutin (RT) after 48 h of CCl4 treatment for four weeks. Antioxidant profile in lungs were evaluated by estimating the activities of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), quinone reductase (QR) and reduced glutathione (GSH). CCl4-induced lipid peroxidation was determined by measuring the level of thiobarbituric acid reactive substances (TBARS) with conjugation of deoxyribonucleic acid (DNA) damages, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology.ResultsAdministration of CCl4 for 6 weeks significantly (p < 0.01) reduced the activities of antioxidant enzymes and GSH concentration while increased TBARS contents and DNA damages in lung samples. Co-treatment of LME and rutin restored the activities of antioxidant enzymes and GSH contents. Changes in TBARS concentration and DNA fragmentation were significantly (p < 0.01) decreased with the treatment of LME and rutin in lung. Changes induced with CCl4 in histopathology of lungs were significantly reduced with co-treatment of LME and rutin.ConclusionResults of present study revealed that LME could protect the lung tissues against CCl4-induced oxidative stress possibly by improving the antioxidant defence system.

Antioxidant and hepatoprotective effects of Oxalis corniculata against carbon tetrachloride (CCl4) induced injuries in rat

Many human diseases are caused due to oxidative stress involving excessive production of free radicals that can be ameliorated by the antioxidant activities of plant extracts. Present study was designed to characterize the chemical composition of Oxalis corniculata methanol extract (OCME) and its various fractions; O. corniculata n-hexane (OCHE), O. corniculataethyl acetate (OCEE), O. corniculata chloroform (OCCE) and O. corniculata aqueous (OCAE); and to determine the antioxidant potential by different in vitro assays. OCME was also evaluated for its antioxidant capacity against hepatotoxicity induced with carbon tetrachloride (CCl4: 1 ml/kg b.w., 20% in olive oil, seven doses) in rat. The results showed the presence of flavonoids, alkaloids, terpenoids, saponins, cardiac glycosides, phlobatannins and steroids in OCME while tannins were absent. Total amount of phenolic and flavonoids was affected by the solvents and the sequence of solvents for phenolic contents was OCME > OCAE > OCCE > OCEE > OCHE while for flavonoids was OCME > OCCE > OCAE > OCEE > OCHE. Free radicals were scavenged by the extract/fraction in a dose response curve in all models. Biochemical parameters of serum; aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (γ-GT), total bilirubin, cholesterol and triglycerides were significantly increased while total protein and albumin were decreased by CCl4. Treatment of CCl4 significantly decreased the liver contents of reduced glutathione (GSH) and activities of antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), glutathione reductase (GSR) and quinone reductase (QR) whereas elevated the thiobarbituric acid reactive substances (TBARS) contents, and hepatic lesions. All the parameters were brought back to control levels by the supplement of OCME. The results of the present study suggest the antioxidant potential of OCME and its fractions as evidenced by scavenging of free radicals and hepatoprotective capacity. Key words: Oxalis corniculata, carbon tetrachloride (CCl4), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS), diphenylpicrylhydrazyl (DPPH), hepatoprotective, lipid peroxidation.

Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4-induced injuries in rats.

BackgroundLaunaea procumbens (Asteraceae) is used as a folk medicine to treat hepatic disorders in Pakistan. The effect of a chloroform extract of Launaea procumbens (LPCE) was evaluated against carbon-tetrachloride (CCl4)-induced liver damage in rats.MethodsTo evaluate the hepatoprotective effects of LPCE, 36 male Sprague–Dawley rats were equally divided into six groups. Animals of group 1 (control) had free access to food and water. Group II received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for 4 weeks. Group III received 1 ml of silymarin via gavage (100 mg/kg b.w.) after 48 h of CCl4 treatment whereas groups IV and V were given 1 ml of LPCE (100 and 200 mg/kg b.w., respectively) after 48 h of CCl4 treatment. Group VI received 1 ml of LPCE (200 mg/kg b.w.) twice a week for 4 weeks. The activities of the antioxidant enzymes catalase, peroxidase (POD), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) were measured in liver homogenates. DNA damage, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology were studied in liver samples. Serum was analyzed for various biochemical parameters. Phytochemical composition in LPCE was determined through high-performance liquid chromatography (HPLC).ResultsLPCE inhibited lipid peroxidation, and reduced the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase in serum induced by CCl4. GSH contents were increased as were the activities of antioxidant enzymes (catalase, SOD, GST, GSR, GSH-Px) when altered due to CCl4 hepatotoxicity. Similarly, absolute liver weight, relative liver weight and the number of hepatic lesions were reduced with co-administration of LPCE. Phyochemical analyses of LPCE indicated that it contained catechin, kaempferol, rutin, hyperoside and myricetin.ConclusionThese results indicated that Launaea procumbens efficiently protected against the hepatotoxicity induced by CCl4 in rats, possibly through the antioxidant effects of flavonoids present in LPCE.

GSH, GSH-related enzymes and GS-X pump in relation to sensitivity of human tumor cell lines to chlorambucil and adriamycin.

Glutathione (GSH) contents and activities of glutathione S-transferase (GST), glutathione reductase (GSH-RD), glutathione peroxidase (GSHpx) and glutathione conjugate export pump (GS-X pump) were determined in eight human tumor cell lines with different sensitivities to adriamycin and chlorambucil. Correlations between sensitivities of the human tumor cells to adriamycin and chlorambucil and the glutathione related factors were analyzed statistically. Sensitivities of the human tumor cells to chlorambucil were found to be correlated to all the glutathione related factors tested (r=0.68-0.88). IC50 values of adriamycin were also positively correlated to GSH contents and activities of GSH-RD, GSHpx and GS-X pump with r values ranging from 0.66 to 0.77 but not to GST activity (r=0.25). Chang liver cells with highest GSH content and highest activities of GST, GSH-RD, GSHpx and GS-X pump were most resistant to both adriamycin and chlorambucil. These data suggested that glutathione related factors may work as an overall detoxification system participating in the detoxification of anticancer drugs such as adriamycin and chlorambucil, and to be involved in cellular resistance to these drugs.

Contribution of antioxidant enzymes to the adaptive response to ionizing radiation of human lymphoblasts

Purpose: To investigate whether the adaptive response to ionizing radiation triggered by a low-dose pre-exposure could be due to the activation of the antioxidant defence system. Materials and methods: Human lymphoblastoid AHH-1 cells were irradiated with a 0.02Gy gamma -radiation and 6h later were exposed to a 3Gy challenge dose according to a protocol allowing mutagenic adaptation. Controls included cells left unirradiated or exposed to a single dose (0.02Gy or 3Gy). The activities of the main cellular antioxidant enzymes (AOE)-copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), glutathione reductase (GSR) and glucose 6-phosphate dehydrogenase (G6PD)-were evaluated at different times after treatment. The levels of SOD2 and CAT proteins were also analysed using the immuno Western blot method. Results: Compared with non-irradiated controls, the effect of 3Gy alone was shown to increase GPX and CAT activities at 20h after irradiation. Pre-exposure of cells did not change these late alterations. Soon after irradiation the activities of SOD2, GST, GPX and CAT were slightly higher in adapted than in nonadapted cells. Conclusion: The data suggest that the increased activities of some AOE observed soon after the challenge dose would result in a rapid scavenging of radicals and consequently less damage in adapted cells. Due to the moderate alterations of these AOE, the activation of antioxidant defences would only partly contribute to the protective mechanism underlying the radioadaptation of AHH-1 lymphoblasts.

Protective effects of antioxidants against uraemia-induced lipid peroxidation and glutathione depletion in humans.

The effects of uraemias and antioxidant therapy for 40 days with vitamin A, vitamin C and vitamin E on blood and erythrocyte sulfhydryl (glutathione, GSH) content and on erythrocyte glutathione-S transferase (GST), glutathione reductase (GSR) and glutathione peroxidase activities were studied in six uraemic patients maintained on haemodialysis. In addition, the effect of antioxidant therapy on erythrocyte lipid peroxidation was determined, and erythrocyte haemoglobin content was measured. Uraemic patients in dialysis exhibited significant decreases in blood and erythrocyte GSH content as well as significant decreases in the activities of GST, GSR and GSH-peroxidase relative to control subjects. Furthermore, the uraemic patients had elevated erythrocyte malondialdehyde levels. Blood and erythrocyte GSH content from uraemic patients was significantly elevated after 20 days of antioxidant treatment and remained elevated thereafter throughout the remaining 20 days of the study (130% and 173%, respectively). Antioxidant therapy also produced significant increases in GSR and GSH-peroxidase activities after 20 days of treatment which remained relatively constant thereafter. No significant change in GST activity was observed. Erythrocyte malondialdehyde levels, as an index of oxidative tissue damage, exhibited a significant decrease (70%) in the patients after 40 days of antioxidant therapy. A gradual increase in erythrocyte haemoglobin content was observed following treatment of the uraemic subjects (45% at day 40). The results suggest that antioxidant therapy may protect against oxidative stress associated with uraemia.