Oxidative stress modulation by Rosmarinus officinalis in creosote‐induced hepatotoxicity

Coal tar is a significant product generated from coal pyrolysis. Coal tar can be utilized as raw materials for various industries. It is also a type of raw material from which phenols, naphthalenes, and anthracene can be extracted. The present study was designed to investigate the possibility of coal tar creosote to induce oxidative stress and biochemical perturbations in rat liver and the role of rosemary (Rosmarinus officinalis) in ameliorating its toxic effects. Male Wister Albino rats were randomly divided into four groups of seven each, group I served as control; group II treated with rosemary (10 mL of water extract/kg BW for 21 days), group III received coal tar creosote (200 mg/4 mL olive oil/kg BW for 3 days), and group IV treated with both rosemary and coal tar creosote. The administration of coal tar creosote significantly caused elevation in lipid peroxidation (LPO) and reduction in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and glutathione S‐transferase (GST). A significant decrease in reduced glutathione (GSH) content was also observed. Liver aminotransferases aspartate transaminase (AST) and alanine transaminase (ALT)] and alkaline phosphatase (AlP) were significantly decreased while lactate dehydrogenase (LDH) was increased. Rosemary pretreatment to coal tar creosote‐treated rats decreased LPO level and normalized GPx, GR, SOD, CAT, and GST activities, while GSH content was increased. Also, liver AST, ALT, AlP, and LDH were maintained near normal level due to rosemary treatment. In conclusion, rosemary has beneficial effects and could be able to antagonize coal tar creosote toxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 85–92, 2016.     

Amelioration of cyclophosphamide-induced hepatotoxicity by the root extract of Decalepis hamiltonii in mice

Hepatoprotective potential of the aqueous extract of the roots of Decalepis hamiltonii (DHA) against cyclophosphamide (CP)-induced oxidative stress has been investigated in mice. Administration of CP (25 mg/kg b.w., i.p) for 10 days induced hepatic damage as indicated by the serum marker enzymes aspartate and alanine transaminases (AST, ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Parallel to these changes CP induced oxidative stress in the liver as evident from the increased lipid peroxidation (LPO), reactive oxygen species (ROS), depletion of glutathione (GSH), and reduced activities of the antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST). Treatment with DHA (50 and 100 mg/kg b.w., po) mitigated the CP-induced oxidative stress. Moreover, expression of genes for the antioxidant enzymes, were down-regulated by CP treatment which was reversed by DHA. Our study shows the DHA protected the liver from toxicity induced by CP and therefore, it could be serve as a safe medicinal supplement during cyclophosphamide chemotherapy.     

Effects of dietary selenium on the oxidative stress and pathological changes in tilapia (Oreochromis niloticus) exposed to a microcystin-producing cyanobacterial water bloom

The present study investigates the role of selenium (Se) supplementation (as sodium selenite) on the oxidative stress and histopathological changes induced by cyanobacterial cells containing microcystins (MCs) in tilapia fish (Oreochromis niloticus). Variation in lipid peroxidation (LPO) levels and carbonyl groups content, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, and catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities in liver and kidney of tilapia fish exposed to a single oral dose of 120 μg MC-LR/fish and sacrificed in 24 h, were investigated in the absence and presence of 1.5, 3.0 and 6.0 μg Se/g diet. Results showed a protective role of Se depending on the dose and the biomarker considered. Thus, the lower Se dose made CAT, liver GR and kidney SOD converged to basal values, whereas LPO and liver SOD and GST needed the higher dose. Kidney GR, however, was not protected at any Se dose. Moreover, Se has also shown to have a pro-oxidant effect with increased kidney LPO values and liver and kidney GPx activities in MC-free fish. The microscopic study revealed tissue alterations induced by cyanobacterial cells in the liver, kidney, heart and gastrointestinal tract that were ameliorated by the highest Se dose assayed. The level of Se supplementation must be therefore carefully selected to provide beneficial effects and to avoid potential negative consequences.     

Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.     

Effect of wastewater intake on antioxidant and marker enzymes of tissue damage in rat tissues: Implications for the use of biochemical markers

In the present study, alteration in antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) and marker enzymes of tissue damage alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) with laboratory exposure to wastewaters from Aligarh (AWW) and Saharanpur (SWW) were investigated in rat liver and kidney. Levels of malondialdehyde (MDA), reduced glutathione (GSH) and hydrogen peroxide (H₂O₂) were also determined.A profound enhancement of 5 and 2.5-folds in MDA level was recorded in the liver and kidney respectively as a result of oral administration of SWW to the rats. Exposure to both AWW and SWW resulted in 3–4-fold increase in GR activity and 3-fold increase in SOD and ALT activity in the hepatic tissue compared to control values. Ingestion of AWW and SWW resulted in 3.5-fold rise in renal AST levels whereas AWW caused 75% decline in GST activity in kidney of treated rats.Results indicate that wastewater (AWW/SWW) caused severe damage to renal and hepatic tissues and the effect seems in part to be mediated by suppression of antioxidant system with GR and SOD as potential candidates for hepatic toxicity biomarkers of wastewaters.     

Caffeic acid phenethyl ester protects against tamoxifen-induced hepatotoxicity in rats

Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. Adverse effects of TAM include hepatotoxicity. Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been used in folk medicine for diverse ailments. In the current study, the protective effects of CAPE against TAM-induced hepatotoxicity in female rats were evaluated. TAM (45 mg/kg/day, i.p., for 10 consecutive days) resulted in an elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), depletion of liver reduced glutathione (GSH) and accumulation of oxidized glutathione (GSSG) and lipid peroxidation (LPO). Also, TAM treatment resulted in inhibition of hepatic activity of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT). Further, it raised liver tumor necrosis factor-alpha (TNF-α) level and induced histopathological changes. Pretreatment with CAPE (2.84 mg/kg/day; i.p., for 20 consecutive days, starting 10 days before TAM injection) significantly prevented the elevation in serum activity of the assessed enzymes. CAPE significantly inhibited TAM-induced hepatic GSH depletion and GSSG and LPO accumulation. Consistently, CAPE normalized the activity of GR, GPx, SOD and CAT, inhibited the rise in TNF-α and ameliorated the histopathological changes. In conclusion, CAPE protects against TAM-induced hepatotoxicity.     

祁州漏芦不同溶剂提取物对急性肝损伤模型小鼠的保护作用

目的:研究祁州漏芦(以下简称"漏芦")不同溶剂提取物对急性肝损伤模型小鼠的保护作用。方法:60只KM种小鼠随机分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、联苯双酯(100 mg/kg)组、漏芦乙醇粗提物(200 mg/kg)组、漏芦正丁醇提取物(200 mg/kg)组和漏芦水提取物(200 mg/kg)组。灌胃给药,每天1次,连续7 d。末次给药1 h后,一次性腹腔注射300 mg/kg对乙酰氨基酚(APAP)以复制小鼠急性肝损伤模型。比色法检测小鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、白蛋白(ALB),肝匀浆丙二醛(MDA)、还原型谷胱甘肽(GSH)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)、谷胱甘肽-S-转移酶(GST),肝线粒体Na+-K+-ATP酶(Na+-K+-ATPase)、Ca2+-Mg2+-ATP酶(Ca2+-Mg2+-ATPase)水平。结果:与正常对照组比较,模型组小鼠血清ALT、AST和ALP活性增强,ALB含量降低;肝组织MDA含量增加,CAT、GPx、SOD、GST活性减弱,GSH含量减少;肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性减弱,差异具有统计学意义(P<0.05)。与模型组比较,漏芦乙醇粗提物组小鼠血清ALT、AST活性减弱,ALB含量增加,肝匀浆MDA含量减少,GSH含量增加,CAT、GPx、SOD、GST活性增强,肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性增强,差异具有统计学意义(P<0.05);漏芦正丁醇提取物组小鼠血清ALT、AST、ALP活性减弱,ALB含量增加,肝匀浆MDA含量减少,GSH含量增加,CAT、GPx、SOD、GST活性增强,肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性增强,差异具有统计学意义(P<0.05);漏芦水提取物组小鼠血清ALT、AST活性减弱,ALB含量增加,肝匀浆MDA含量减少,GSH含量增加,GPx、GST活性增强,肝线粒体Na+-K+-ATPase和Ca2+-Mg2+-ATPase活性增强,差异具有统计学意义(P<0.05)。结论:漏芦不同溶剂提取物对APAP致小鼠急性肝损伤具有保护作用,其机制可能与其抗氧化作用有关。     

Pectolinarin and Pectolinarigenin of Cirsium setidens Prevent the Hepatic Injury in Rats Caused by D-Galactosamine via an Antioxidant Mechanism

To identify the hepatoprotective component from the leaves of Cirsium setidens (Compositae), the methanolic extract was divided into two fractions, chloroform and butanol fractions, and their hepatoprotective efficacy was evaluated in a rat model of hepatic injury caused by D-galactosamine (GalN). Hepatoprotective activity was measured by the activity of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Glutathione metabolism was measured via biochemical parameters such as glutathione (GSH), glutathione reductase (GR), gamma-glutamylcysteine synthetase (GCS), glutathione S-transferase (GST), and superoxide dismutase (SOD) levels. We subjected the butanol fraction, which had higher activity, to column chromatography to yield pectolinarin, which was further hydrolyzed to yield pectolinarigenin. Administration (10, 20 mg/kg, p.o.) of the main flavonoid glycoside component, pectolinarin, and its aglycone, pectolinarigenin, for 2 weeks significantly decreased the activity levels of AST, ALT, ALP and LDH, indicating that the two compounds have hepatoprotective activity. Pectolinarin and pectolinarigenin also increased activity levels of GSH, GR, GCS, and GST, as well as SOD. The significant effect was only seen in SOD activity. This suggests that the two components exhibit hepatoprotective activity mainly via SOD antioxidant mechanism.     

Quercetin attenuates lambda cyhalothrin‐induced reproductive toxicity in male rats

The aim of this study was to evaluate the possible protective effects of Quercetin (Qe) against oxidative stress induced by λ cyhalothrin (LTC) in reproductive system. Thirty‐two male rats were divided into four groups. First group was allocated as the control group. Second group was given a Qe alone while the third group received a LTC alone. Animals in the fourth group were given a Qe with LTC. Caudae epididymis was removed for sperm analysis. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), and reduced glutathione (GSH) were determined in the testis. Additionally, the different histopathologic changes were observed in the testis of animals. LTC exposure significantly increased the abnormal morphology and LPO. On the contrary, sperm motility, viability and count, levels of GSH, and activities of SOD, CAT, GPx, and GST were significantly decreased compared to controls. Qe with LTC offset the decrease in functional sperm parameters, antioxidants enzymatic activities, and nonenzymatic antioxidant levels when compared with LTC‐treated rats. Furthermore, LTC showed irregular seminiferous tubules containing only Sertoli cells and Qe with LTC caused regular seminiferous tubules showing spermatogenesis at level of spermatocytes. We conclude that LTC‐induced oxidative stress and functional sperm parameters in male rats, and dietary of Qe attenuates the reproductive toxicity of LTC to restore the antioxidant system and sperm parameters in male rats. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 673–680, 2013.     

Piperine as an adjuvant increases the efficacy of curcumin in mitigating benzo(a)pyrene toxicity

In the present study, the antioxidative and anticlastogenic effects of curcumin and piperine separately and in combination have been investigated against benzo(a)pyrene (BaP)-mediated toxicity in mice. Male Swiss albino mice were pretreated with curcumin (100 mg kg(-1) body weight) and piperine (20 mg kg(-1) body weight) separately as well as in combination orally in corn oil for 7 days; and subsequently, after 2 h of pretreatment, BaP was administered orally in corn oil (125 mg kg(-1) body weight). A single dose of BaP in normal mice increased the levels of lipid peroxidation (LPO), protein carbonyl content (PCC), and frequency of bone marrow micronucleated polychromatic erythrocytes (MNPCEs) but decreased significantly the levels of endogenous antioxidants such as superoxide dismutases (SODs), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and reduced glutathione (GSH) in the liver. Pretreatments with curcumin and curcumin plus piperine before administration of single dose of BaP significantly decreased the levels of LPO, PCC, and incidence of MNPCEs but elevated the level of GSH and enzyme activities of GPx, GR, SOD, CAT, and glutathione-S-transferase (GST) when compared to the BaP-treated group. The effect of curcumin plus piperine is more pronounced as compared to curcumin in attenuating BaP-induced oxidative insult and clastogenicity.     

The effects of fucoidan extracts on CCl<Subscript>4</Subscript>-induced liver injury

The aim of this study was to elucidate the antioxidant properties of fucoidan extracts (FE) against CCl(4)-induced oxidative stress by monitoring the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Female, Sparague-Dowley rats were administered with FE (100 mg/kg daily) for 14 days and CCl(4) on the 15'th day, 12 h before they were sacrificed. The levels of GOT, GPT, ALP and LDH in serum of rats, as well as the levels of MDA, SOD, CAT and GPx in total liver homogenate were analyzed. CCl(4)-treatment was found to increase the levels of GOT, GPT, ALP, LDH and MDA, as well as decrease levels of SOD, CAT and GPx significantly. The pre-treatment of rats with FE, however, suppressed the increment of levels of GOT, GPT, ALP, LDH and MDA, as well as recovered the levels of SOD, CAT and GPx in CCl(4)-treated rats. Moreover there was a significant decrease in incidences of necrosis and cirrhosis in the liver tissue of FE-treated rats. These results implied that FE possessed antioxidant properties against CCl(4)-induced oxidative stress.     

The role of vitamin C as antioxidant in protection of oxidative stress induced by imidacloprid

Pesticides may induce oxidative stress leading to generate free radicals and alternate antioxidant or oxygen free radical scavenging enzyme system. This study was conducted to investigate the acute toxicity of imidacloprid toward male mice and the oxidative stress of the sublethal dose (1/10 LD₅₀) on the lipid peroxidation level (LPO), reduced glutathione content (GSH) and activities of the antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-s-transferase (GST). Also, the protective effect of vitamin C (200 mg/kg bw) 30 min before or after administration of imidacloprid were investigated. The results demonstrated that the median lethal dose (LD₅₀) of imidacloprid after 24 h was 149.76 mg/kg bw. The oral administration of 14.976 mg/kg imidacloprid significantly caused elevation in LPO level and the activities of antioxidant enzymes including CAT, SOD, GPx and GST. However, G6PD activity remained unchanged, while the level of GSH content was decreased. In addition, the results showed that vitamin C might ameliorate imidacloprid-induced oxidative damage by decreasing LPO and altering antioxidant defense system in liver. The protective effect of the pre-treatment with vitamin C against imidacloprid-induced oxidative stress in liver mice is better than the post-treatment.     

Differential oxidative stress responses to pure Microcystin-LR and Microcystin-containing and non-containing cyanobacterial crude extracts on Caco-2 cells

Cyanobacterial blooms are a worldwide problem due to the production of cyanotoxins such as microcystins (MCs), causing serious water pollution and public health hazard to humans and livestock. Oxidative stress plays a significant role in MCs toxicity. In the present work the differential oxidative stress responses to pure MCs, and Microcystin-containing and non-containing cyanobacterial crude extracts on the human colon carcinoma cell line Caco-2 has been studied for the first time. After exposure, cells were collected and the antioxidant enzymes activities superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were measured. Moreover, lipid peroxidation (LPO) induction, reactive oxygen species (ROS) and reduced glutathione (GSH) content were also analyzed. The oxidative stress biomarkers that experienced higher alterations were ROS, CAT, SOD and GR activities. The MC containing cyanobacterial extract showed the higher toxic effects, followed by pure MC-LR. The non-MC containing cyanobacterial extract showed limited effects mainly in SOD activity, GSH content, and GP and GR activities only at the highest concentration used. These results suggest that MC-LR is the responsible of the oxidative stress responses observed in Caco-2 cells, but other compounds contained in the cyanobacterial extracts can contribute to the toxic effects.     

Genotoxicity assessment and oxidative stress responses in freshwater African catfish Clarias gariepinus exposed to fenthion formulations

Fenthion is one of the most widely used organophosphate insecticides for the control of many varieties of pests in Nigeria. The genotoxic effect of the pesticide was evaluated in the blood erythrocytes of Clarias gariepinus using the micronucleus (MN) test. The oxidative stress parameters were also studied in the liver and gill tissues. Fish were exposed to 2.0, 4.0, and 8.0?mgL^?1 of fenthion and sampling was done on days 1, 7, 14, 21 and after 7-day recovery. Micronuclei induction was highest (7.55) on day 14 at all concentrations in the peripheral blood cells. Oxidative stress was evidenced by increased lipid peroxidation (LPO). Maximum LPO values of 62.47% and 71.17% were observed in the gill and liver tissues respectively in C. gariepinus exposed to 8.0?mgL^?1 concentration of fenthion. There were alterations in the values of reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) during the exposure and recovery periods. The 7-day recovery period was not adequate to eliminate fenthion-induced changes as LPO, CAT, and GR activity remain elevated. However, MN frequency and activity of SOD, GSH, and GPx (except at 8.0?mgL^?1) recovered. The present findings give further credence on the integrated use of MN test and oxidative stress parameters in risk assessment of pollutants in aquatic ecosystem.     

The peroxisome proliferator‐activated receptor‐γ agonist pioglitazone protects against cisplatin‐induced renal damage in mice

Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non‐diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR‐γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg^–1). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg^–1 day^–1, per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non‐enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S‐transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin‐induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR‐γ agonists in human application for protecting against drugs‐induced nephrotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.     

Silymarin: An Effective Hepatoprotective Agent Against Diethylnitrosamine-Induced Hepatotoxicity in Rats

Abstract

This study investigates the putative hepatoprotective and antioxidant activity of silymarin (SIL) on diethylnitrosamine (DEN)-induced liver damage in male Wistar rats. A single intraperitoneal administration of DEN (200 mg/kg) to rats resulted in significantly elevated serum levels of AST, ALT, ALP, LDH, γ-GT, and BIL compared with controls after 30 days in serum. In contrast, the liver tissue showed a significant decrease in the levels of AST, ALT, and ALP, and an increase in LDH and γ-GT. Elevated levels of lipid peroxidation (LPO) were observed in the liver tissue after DEN administration. Quantitative analysis of catalase (CAT) and superoxide dismutase (SOD) revealed lower activities of these key antioxidant enzymes in the liver upon DEN administration. The status of antioxidant vitamins, vitamin C and vitamin E, were also found to be decreased in DEN-exposed rats. When rats with DEN-induced hepatotoxicity were treated with SIL (50 mg/kg, orally) for 30 days, the levels of AST, ALT, ALP, LDH, γ-GT, and BIL reverted to near normalcy, whereas the hepatic concentration of CAT, SOD, vitamin C, and vitamin E were significantly increased, and that of LPO significantly lowered, when compared with DEN-exposed, untreated rats. These results suggest that SIL is able to significantly alleviate the hepatotoxicity and oxidative stress induced by DEN in rats.     

Lipid peroxidation and antioxidant status in kidney and liver of rats treated with sulfasalazine

Sulfasalazine (SASP) is a drug commonly used in the treatment of inflammatory bowel diseases (IBD). In this study, the changes in endogenous antioxidant capacity and oxidative damage in liver and kidney of SASP-treated rats were investigated. Adult male Sprague–Dawley rats were orally given 0, 300, or 600 mg SASP/kg body weight for 14 days. One half of the animals in each group remained 14 additional days without SASP treatment. At the end of the experimental period, rats were euthanized and liver and kidney were removed. In both organs, the following stress markers were determined: reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid-reactive substances (TBARS). Moreover, histological examination of kidneys showed phagolysosomes after 14 days of SASP withdrawal. A dropsical degeneration was also observed in renal tissue. Oral SASP administration induced a significant increase in TBARS levels in both liver and kidney. After 2 weeks without SASP administration, a recovery of these levels was noted. SOD activity was significantly reduced, while CAT activity significantly increased at 600 mg SASP/(kg day). In kidney, GPx activity significantly increased, while GST activity and GSH levels were significantly reduced at 600 mg SASP/(kg day). These results suggest that in male rats, oxidative damage can be a mechanism for nephro- and hepatotoxicity related with SASP treatment.     

Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats

Aim and Objectives:

In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats.

Materials and Methods:

PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed.

Results:

The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group).

Conclusion:

Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems.     

Amelioration effects against N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera

Objective:

The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis.

Materials and Methods:

The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl₄), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl₄, treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups.

Results:

The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl₄ -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group.

Conclusion:

These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl⁴-induced two-stage hepatocarcinogenesis.