Aquilegia vulgaris L. extract counteracts oxidative stress and cytotoxicity of fumonisin in rats

Exposure to fumonisins (FB) is known to have toxic and carcinogenic effects in different animal species, and to express toxicity in cells via the induction of oxidative stress. The aim of the current study was to evaluate the protective effects of the ethanol extract of Aquilegia vulgaris L. against the oxidative stress and the genotoxicity using micronucleus assay and random amplified polymorphism DNA (RAPD-PCR) in FB-treated rats. Sixty mature female Sprague-Dawley were divided into six treatment groups and treated for 4 weeks as follow: the control group, the group fed FB-contaminated diet (200 mg/kg diet), the groups treated orally with the extract (5 and 10 mg/kg bw) and the groups fed FB-contaminated diet and treated with the extract at the two doses. The results showed that treatment with FB alone disturbed lipid profile in serum, increases Sa/So ratio, induces micronucleated polychromatic erythrocytes (Mn-PCEs) in bone marrow, increases DNA and RNA in liver accompanied with significant changes in histological picture The extract alone at the two tested doses did not induce any significant changes in the biochemical or histological picture. The combined treatment showed significant improvements in all biochemical, cytogenetic parameters tested and histological pictures in the liver tissues. Moreover, this improvement was more pronounced in the group received the high dose of the extract. It could be concluded that the ethanol extract of A. vulgaris induced its protective effect via the increase in the antioxidant capacity, inhibition of lipid peroxidation and scavenging of free radicals.     

Tissue-specific changes in glutathione content of hypoxic newborn pigs reoxygenated with 21% or 100% oxygen

We compared the responses towards oxidative stress in the liver, lung, brain, heart, kidney and small intestine of hypoxic newborn animals resuscitated with 21% or 100% oxygen. After stabilization, piglets (1-3 days, 1.6-2.0 kg, n=8/group) were randomized to receive 2 h of alveolar hypoxia (FiO(2)=0.10-0.14) followed by reoxygenation with 21% or 100% oxygen for 1 h and then another hour with 21% oxygen. Controls were sham-operated without hypoxia-reoxygenation. At the end of the experiment, tissues from liver, lung, brain, heart, kidney and small intestine were collected and tested for GSH, GSSG and lipid peroxidation levels and histological examination. In normoxic controls, liver had the highest GSH level, followed by brain, heart, lung, small intestine and kidney which had the highest level of oxidative stress markers (GSSG level and GSSG:GSH ratio). Hypoxic-reoxygenated piglets had the highest GSSG levels and GSSG:GSH ratio in the kidney. Hypoxic piglets resuscitated with 100% oxygen had higher GSSG:GSH ratios in the lung and liver, but not in the kidney, brain, heart and small intestine, than controls, which were not different from the 21% group. No significant differences in peroxidation and histological tissue damage were found between groups in the liver and lung. We concluded that although hypoxic piglets resuscitated with 100% oxygen have higher oxidative stress in the liver and lung than with 21% oxygen, there are no significant differences in peroxidation and histological tissue damage acutely.     

Effect of Centella asiatica on arsenic induced oxidative stress and metal distribution in rats

Concomitant oral supplementation of Centella asiatica (100, 200 or 300 mg kg(-1), orally once daily) during arsenic exposure (20 ppm in drinking water for 4 weeks) was investigated in rats for its protective value. The animals exposed to arsenic (III) showed a significant inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity, a marginal decrease in glutathione (GSH) and an increase in zinc protoporphyrin (ZPP) level in blood. Hepatic and renal glutathione (GSH) decreased, while oxidized glutathione (GSSG) and thiobarbituric acid reactive substance (TBARS) levels increased significantly in the liver, kidney and brain. The activities of brain superoxide dismutase (SOD) and catalase decreased marginally on arsenic exposure. Concomitant administration of Centella asiatica showed a significant protective action on inhibited blood ALAD activity and restored the blood GSH level, whereas most of the other blood biochemical parameters remained unchanged on Centella asiatica supplementation. Interestingly, most of the hepatic biochemical variables indicative of oxidative stress showed protection. There was, however, a significant protection observed in the altered kidney GSSG level and hepatic and brain TBARS. Only a marginal beneficial effect of Centella asiatica on blood and liver arsenic concentration was noted, particularly at the highest dose studies (300 mg kg(-1)). No effect of Centella asiatica on most of the altered renal biochemical parameters was noted. The results thus lead to the conclusion that simultaneous supplementation of Centella asiatica significantly protects against arsenic-induced oxidative stress but does not influence the arsenic concentration in these organs. It can thus be suggested that co-administration of Centella asiatica protects animals from arsenic-induced oxidative stress but exhibits no chelating property. Further studies are recommended for determining the effect of co-administration of Centella asiatica during chelation therapy with a thiol chelator.     

Comparison of the protective effects of antioxidant compounds in the liver and kidney of Cd‐ and Cr‐exposed common carp

The aim of this study was to see whether the taurine (TAU), alpha‐lipoic acid (LA), curcumin (CUR), and N‐acetylcysteine (NAC) protection against oxidative stress caused by heavy metals is owed to the metal‐decreasing or antioxidative effect. In this context, liver and kidney tissues of common carp (Cyprinus carpio carpio L.) were exposed in vivo to model toxicants cadmium (Cd) and chromium (Cr). The tissues were dissected 96 h after intraperitoneal injection of the metals and antioxidant substances. Cd and Cr levels were determined in the liver using the ICP‐OES, but we could not obtain enough kidney tissue to make the same measurements in the kidney. The enzymatic activities of SOD, CAT, and GPx, and the GSH redox status and lipid peroxidation levels were analyzed using spectrophotometric methods. Of all investigated antioxidants, only NAC decreased metal levels in the liver. Cd had little effect on oxidative stress parameters, while Cr showed a weak prooxidative effect. Cotreatment with TAU/LA/CUR/NAC and Cr significantly increased liver SOD activity. Chromium induced kidney SOD and CAT, but all antioxidants lowered CAT activity. Cadmium reduced liver and increased kidney GSSG. NAC increased liver GSH, but the increase did not correlate with decrease in Cd. Curcumin given with Cd increased kidney and decreased liver lipid peroxidation, whereas TAU with Cr increased lipid peroxidation in both tissues. N‐Acetylcysteine was the most effective antioxidative agent, owing to its metal‐decreasing function as well as to its effects on the GSH redox status. We believe that the investigated antioxidant substances which may have been involved in the reduction of Cr caused an increase in SOD activity and a decrease in CAT activity. Changes in the GSSG levels in both tissues might be an adaptive response to the prooxidative potential of Cd. Because of their respective tissue‐ and metal‐dependent prooxidative effects, CUR and TAU deserve particular attention in regard to their use against metal toxicity, Cr in particular. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 129–137, 2014.     

Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats

Alpha-lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead induced oxidative stress. These results suggested its possible role as a therapeutic intervention of lead poisoning in combination with a chelator. We investigated the effects of LA, either alone or when administered in combination with succimer (meso 2,3-dimercaptosuccinic acid; DMSA or one of its analogue monoisoamyl DMSA), in influencing the lead induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from blood and soft tissues. The results suggest a significant lead induced inhibition of delta-aminolevulinic acid dehydratase (ALAD), reduction in glutathione (GSH) and an increased zinc protoporphyrin (ZPP) level in blood, indicating altered heme synthesis pathway. Both the thiol chelators were able to increase blood ALAD activity and GSH level towards normal. The most prominent effect on blood ALAD activity was however observed when monoisoamyl DMSA (MiADMSA) was co-administered with LA. Lead exposure produced significant depletion of hepatic GSH, while, oxidized glutahione (GSSG), thiobarbituric acid reactive substances (TBARS) and catalase activity increased significantly, suggesting hepatic oxidative stress. All the treatments were able to increase hepatic GSH and reduce GSSG levels, while, TBARS level reduced significantly in animals administered LA and MiADMSA, individually or in combination. Lead induced increase in renal GSSG, TBARS levels and catalase activity, were effectively reduced by LA, while, the two chelators when administered alone were effective only in reducing GSSG and catalase activity. The most prominent beneficial effects, however, were observed in animals treated concomitantly with LA and one of the chelators (DMSA or MiADMSA). Brain GSH and GSSG levels decreased moderately while superoxide dismutase (SOD) activity remained statistically unaltered on lead exposure. Brain catalase activity, on the other hand, increased significantly. Administration of LA was effective in reducing these alterations in the brain, however, the best effects were achieved in animals co-administered LA and one of the thiol chelators. The results point to a significant beneficial role of LA in the recovery of altered biochemical variables both during monotherapy and when given in combination with succimer. It however, showed no chelating properties in decreasing lead burden from blood, liver and kidneys except for a significantly more pronounced decrease in brain lead concentration in animals administered LA plus thiol chelators, compared to the effects of chelating agents alone. This is an interesting and notable observation, which requires further exploration. The results thus provide evidence of an encouraging role of LA when given in combination with a thiol chelator in the therapeutic intervention of lead poisoning, particularly in reducing the oxidative stress and brain lead concentration.     

Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced oxidative stress and biochemical alterations in rats

Oxidative stress due to enhanced production of free radicals has been incriminated as one of the several mechanisms involved in arsenic-induced toxic effects in different organs. In the present study, ameliorative potential of certain amino acids like cysteine, methionine and vitamins like ascorbic acid and thiamine on some of the parameters indicative of oxidative stress in liver, kidney and blood and of hepatic and renal infliction was investigated in arsenic exposed rats. Rats were given 0 ppm (group I healthy controls) or 10 ppm arsenic in drinking water ad lib for a period of 12 weeks. During oral exposure to arsenic rats of different groups received daily oral dose of placebo, cysteine, methionine, ascorbic acid or thiamine at 25mg/kg body weight. After the end of the experimental period, animals were sacrificed under light anesthesia and blood, liver and kidney were collected. Samples were processed for estimation of arsenic, biochemical parameters indicative of oxidative stress and hepatic and renal function. Arsenic exposure resulted in significantly (P<0.05) higher accumulation of arsenic in blood, liver and kidney. It was associated with significant (P<0.05) rise in lipid peroxide level and decrease in superoxide dismutase and catalase activities in liver and kidneys. However, alterations in biochemical parameters did not reach statistical (P>0.05) significance. Treatment with vitamins and amino acids resulted in reversal of oxidative stress with significant (P<0.05) decline in tissue arsenic burden. All the treatment produced tissue specific changes in lipid peroxide level, antioxidant enzyme activities and tissue arsenic burden.     

Ability of Lactobacillus casei and Lactobacillus reuteri to protect against oxidative stress in rats fed aflatoxins-contaminated diet

Lactic acid bacteria (LAB) have been reported to remove mycotoxins from aqueous solutions through a binding process, which appears to be species and strain specific. The aim of the current study was to evaluate the protective role of Lactobacillus casei (L1) and Lactobacillus reuteri (L2) against aflatoxin (AFs)-induced oxidative stress in rats. Sixty female Sprague-Dawley rats were divided into 6 groups including the control group and the groups treated with L1 or L2 (1 × 10¹¹/ml) alone at a dose of 10 ml/kg b.w or plus AFs (3 mg/kg diet) for 4 weeks. At the end of the treatments, blood and tissue samples were collected for biochemical and histological studies. The results indicated that AFs alone induced a significant decrease in food intake and body weight and a significant increase in transaminase, alkaline phosphatase cholesterol, triglycerides, total lipids, creatinine, uric acid and nitric oxide in serum and lipid peroxidation in liver and kidney accompanied with a significant decrease in total antioxidant capacity. Treatments with L1 or L2 succeeded to induce a significant improvement in all the biochemical parameters and histological picture of the liver. Moreover, L2 was more effective than L1 and both can be used safely in functional foods.     

Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry,histopathology and NMR‐based metabonomic approach

In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and ¹H‐NMR‐based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β‐oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α‐ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments. Copyright © 2014 John Wiley & Sons, Ltd.     

Cadmium accumulation in organs and mortality during a continued oral uptake

Paste-form food containing cadmium (10 ppm or 50 ppm) was administered to rats (Wistar strain, ♀) in a long-term study of cadmium content in the organs and mortality rate. The following results were obtained:

1. Cadmium intake (10 ppm or 50 ppm) led to an immediate reduction of food consumption and growth. As a result of 41 weeks of cadmium intake, the cadmium accumulation rate in the kidney and liver of the 10 ppm group (0.47%) did not differ from that of the 50 ppm group (0.53%). However, the distribution rate of cadmium to the kidney or liver depended on its concentration. With a 10 ppm intake, the kidney contained the same amount of cadmium as the liver, but with a 50 ppm intake it contained only one fourth of that in the liver.
2. In the case of 50 ppm cadmium intake, the mortality was increased significantly beginning with the 28th week of intake coinciding with rapid increase of cadmium in the kidney and liver. Histologically, tubular damage was observed in the kidney.

     

Characterization of bioactive compounds and ameliorative effects of Ceratonia siliqua leaf extract against CCl4 induced hepatic oxidative damage and renal failure in rats

Ceratonia siliqua is a typical Mediterranean plant, mainly used in food and Tunisian traditional folk medicine. Among the tested extracts, the ethyl acetate fraction (EACs) exhibited the highest total phenolic and flavonoids content. The antioxidant activity in vitro systems showed a more significant potent free radical scavenging activity of this extract than other analysis fractions. The HPLC finger print of EACs active extract showed the presence of six phenolic compounds. The in vivo results showed that oral administration of CCl₄ enhanced levels of hepatic and renal markers (ALT, AST, ALP, LDH, γ-GT, urea and creatinine) in the serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a concomitant decrease in the levels of enzymatic antioxidants (SOD, CAT, GPx) in both liver and kidney. The pre-treatment of experimental rats with 250 mg/kg (BW) of the EACs, by intraperitoneal injection for 8 days, prevented CCl₄ induced disorders in the levels of hepatic and kidney markers. The biochemical changes were in accordance with histopathological observations suggesting a marked hepatoprotective and nephroprotective effect of the EACs extract.     

Probing the anti-hyperlipidemic efficacy of the allspice (Pimenta officinalis Lindl.) in rats fed with high fat diet

In this study, the anti-hyperlipidemic effect of aqueous extract of Pimenta officinalis (APO) was investigated in experimental rats fed with high fat diet (HFD). Hyperlipidemia in experimental rats was evidenced by a significant enhancement in the level of glycerol, triglycerides and phopholipids in serum, and also in liver and kidney tissues. HFD caused oxidative stress in these animals as shown by marked increment in the levels of thiobarbituric acid reactive substances (TBARS) and diene conjugates (CD), and a distinct diminution in reduced glutathione (GSH) content in liver and kidneys. Antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) showed reduced activity in hyperlipidemic rats. All these biochemical parameters showed reliable signs of retrieving towards near-normalcy in APO-administered HFD fed rats. This study unveiled the anti-hyperlipidemic as well as antioxidant activity of APO.     

α‐Lipoic acid protects against microcystin‐LR induced hepatotoxicity through regeneration of glutathione via activation of Nrf2

Microcystins (MCs), as the most dominant bloom‐forming strains in eutrophic surface water, can induce hepatotoxicity by oxidative stress. Alpha‐lipoic acid (α‐LA) is a super antioxidant that can induce the synthesis of antioxidants, such as glutathione (GSH), by nuclear factor erythroid 2‐related factor 2 (Nrf2). However, the potential molecular mechanism of α‐LA regeneration of GSH remains unclear. The present study aimed to investigate whether α‐LA could reduce the toxicity of MCs induced in human hepatoma (HepG2), Bel7420 cells, and BALB/c mice by activating Nrf2 to regenerate GSH. Results showed that exposure to 10 μM microcystin‐leucine arginine (MC‐LR) reduced viability of HepG2 and Bel7402 cells and promoted the formation of reactive oxygen species (ROS) compared with untreated cells. Moreover, the protection of α‐LA included reducing the level of ROS, increasing superoxide dismutase activity, and decreasing malondialdehyde. Levels of reduced glutathione (rGSH) and rGSH/oxidized glutathione were significantly increased in cells cotreated with α‐LA and MC‐LR compared to those treated with MC‐LR alone, indicating an ability of α‐LA to attenuate oxidative stress and MC‐LR‐induced cytotoxicity by increasing the amount of rGSH. α‐LA can mediate GSH regeneration through the Nrf2 pathway under the action of glutathione reductase in MC‐LR cell lines. Furthermore, the data also showed that α‐LA‐induced cytoprotection against MC‐LR is associated with Nrf2 mediate pathway in vivo. These findings demonstrated the potential of α‐LA to resist MC‐LR‐induced oxidative damage of liver.     

Antioxidant and anti-inflammatory effects of Nasturtium officinale involved in attenuation of gentamicin-induced nephrotoxicity

Background and purpose: Gentamicin (GM) is used against bacterial infections. The aim of our investigation was to evaluate the role of inflammation and also oxidative damage in nephrotoxic potential of GM and protective effects of Nasturtium officinale (watercress) against GM-induced nephrotoxicity in Wistar rats.

Material and methods: The animals were divided into eight groups: control, solvent, GM (80?mg/kg IP), GM with three doses (50, 100 and 200?mg/kg/d) of hydroalcoholic extract of watercress and one group only received high dose of extract and a group which received GM plus vitamin E for 10 consecutive days. Then, the animals were killed and kidney tissues were separated. Finally reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation (LPO), protein carbonyl (PCO), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated. Also, pathological examination and measuring of blood urea nitrogen (BUN) and creatinine (Cr) were done.

Results: The administration of GM for 10 d resulted in an increase in kidney markers (BUN and Cr) and pathological changes in kidney tissue. Also, oxidative stress was evident in GM group by increased ROS, LPO and PCO level and GSH oxidation. Increased in inflammation process was shown by increase in NO and TNF-α. Administration of watercress extract was able to protect against deterioration in nephrotoxic markers and suppressed the increase in oxidative stress and inflammation markers.

Conclusions: Our study showed the critical role of oxidative damage and inflammation in GM-induced nephrotoxicity that markedly inhibited by administration of watercress. Therefore, watercress can be suggested for prevention of GM-induced nephrotoxicity.     

Protective effect of lycopene on gentamicin-induced oxidative stress and nephrotoxicity in rats

A potential therapeutic approach to protect or reverse gentamicin-induced oxidative stress and nephrotoxicity would have more importance for clinical consequences. Therefore, the present study was designed to investigate the possible protective effects of lycopene against gentamicin-induced renal damage in rats. Male Sprague-Dawley rats were divided into four groups of six rats in each one; first group served as control. The other groups were treated intraperitoneally with gentamicin alone (100 mg kg(-1) per day) for six successive days, gentamicin for 6 days following 10 days of orally lycopene (4 mg kg(-1) per day) pre-treatment and 6-days of simultaneous lycopene and gentamicin. Biochemical and histopathological examinations were utilized for evaluation of the oxidative stress and renal nephrotoxicity. Creatinine, urea, Na(+) and K(+) levels in plasma and malondialdehyde (MDA), reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) and catalase (CAT) activities were determined in kidney tissue. Administration of gentamicin to rats induced a marked renal failure, characterized by a significant increase in plasma creatinine and urea concentrations. The animals treated with gentamicin alone showed a significantly higher kidney MDA and lower GSH-Px and CAT activities but unaffected GSH concentrations when compared with the control group. Pre-treatment with lycopene produced amelioration in biochemical indices of nephrotoxicity in plasma. However, little changes were observed in the kidney MDA and GSH levels and GSH-Px and CAT activities when compared with the gentamicin treated group. The histological structures of the renal proximal tubules showed similar patterns. On the other hand, administration of simultaneous lycopene to rats produced amelioration in MDA and GSH levels and GSH-Px and CAT activities when compared with gentamicin group. In addition, simultaneous lycopene was found to reduce the degree of kidney tissue damage in histopathological findings. These results indicate that specially simultaneous treatment of lycopene might have produced amelioration in biochemical indices and oxidative stress parameters against gentamicin-induced nephrotoxicity, but pre-treatments with lycopene had no beneficial effects on these parameters. It was concluded that lycopene as a novel natural antioxidant might have protective effects against gentamicin-induced nephrotoxicity and oxidative stress in rats.     

Immunomodulatory and antioxidant protective effect of Sarcocornia perennis L. (swampfire) in lead intoxicated rat

Lead (Pb) is a very toxic metal present in the environment, causing disturbances of several functions. Preventive or curative effects of halophytic plants against these disorders may be a promising and safe therapeutic strategy. Thus, this study was designed to evaluate in vivo immunomodulatory and antioxidant effects of Sarcocornia perennis extract (Sp) against lead toxicity in rats. Groups of six animals each were treated with plant extract (via food), 6?g/L lead acetate (via drinking water) or a combination of both. At the end of the three-week period, rat exposure to lead caused reduction of liver weight but an increase of that of kidney. Moreover, lead intoxication-induced oxidative stress manifested by significant increases of inflammatory cytokines (except IL-10) and lipid peroxidation (TBARS), compared with the control group. Meanwhile, interleukin-10 (IL-10) and glutathione levels (GSH), as well as antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were decreased. Considering liver and renal markers, lead treatment induced a significant increase in the activities of aminotransferases (AST, ALT), and in the levels of urea, creatinine and phosphorous, whereas total plasma protein, albumin and calcium levels were significantly decreased. S. perennis extract alone did not induce any significant changes in hepatic or renal markers, whereas the antioxidant markers were significantly increased. S. perennis supplementation significantly reduced the lead-induced elevation of serum IL-1ß, IL-6, TNF-α, IFN-γ and TBARS but increased the IL-10 and antioxidant enzyme activities. Overall, plant components ameliorated hepatorenal damages caused by lead.     

Effects of fluoride on the tissue oxidative stress and apoptosis in rats: biochemical assays supported by IR spectroscopy data

The mechanism underlying the toxicity of fluoride still remains unknown. To investigate the effects of different doses of fluoride on blood and tissue oxidative stress and apoptosis, we exposed male rats to three doses of fluoride (10, 50 and 100ppm in drinking water) for a period of 10 weeks. The results suggested that exposure to 10ppm fluoride significantly increased the level of reactive oxygen species (ROS) in blood accompanied by a decrease in glutathione (GSH) level. No evidences of oxidative stress in soft tissues were seen. Fluoride (10ppm) also decreased GSH/GSSG ratio significantly. Contrary to expectation, 50 and 100ppm fluoride exposure did not produce a more pronounced toxicity in the soft tissues. However, we observed a significantly elevated concentration of ROS and depleted GSH level in blood. Exposure to fluoride did not produce any sign of apoptosis. To support our above mentioned biochemical observations and to suggest possible mechanism of action of fluoride, IR spectra of brain tissues were recorded. The results of these spectra indicated significant shift in the characteristic peak of -OH group in animals exposed to 10ppm fluoride however at higher doses, the shift was minimal. It can thus be concluded that fluoride-induced toxicity is mediated through oxidative stress particularly at a comparatively lower level of exposure however at the higher doses the mode of action still unclear and needs further investigation.     

Aqueous extract of the bark of <Emphasis Type="Italic">Terminalia arjuna</Emphasis> plays a protective role against sodium-fluoride-induced hepatic and renal oxidative stress

Fluoride is an environmental and industrial pollutant. It has already been reported that the accumulation of fluoride can alter the activities of some enzymes involved in the free-radical metabolism and also decrease the activities of some enzymes involved in the antioxidant defense system. In the present study, we have investigated the antioxidative properties of aqueous extract of the bark of Terminalia arjuna (TA) on sodium fluoride (NaF) induced oxidative damages in the livers and kidneys of Swiss albino mice. The mice were treated with 600 ppm NaF for one week in drinking water and the activities of antioxidant enzymes, like superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST), and the levels of non-protein thiol, reduced glutathione (GSH), along with lipid peroxidation in the liver and kidney, were determined. Fluoride administration significantly altered the levels of all of the factors compared to that of normal mice. Dose- and time-dependent studies suggest that the aqueous extract of the bark of TA showed optimum protective activity against NaF-induced oxidative damages at a dose of 40 mg/kg body weight for 10 days. Oral administration of the extract for the specified dose and time followed by NaF treatment (600 ppm) normalized the levels of the hepatic and renal antioxidant enzymes, GSH, and lipid peroxidation significantly to almost normal levels. The effects of a known antioxidant, vitamin E, and a non-relevant agent, bovine serum albumin (BSA), have also been included in the study. In addition, TA extract has been found to possess radical scavenging activity. Combining all of the data, the results suggest that TA might possess a protective role against NaF-induced hepatic and renal oxidative damages, probably via its antioxidant properties. Mahua Sinha and Prasenjit Manna contributed equally in the study.     

Antioxidant potential of the methanol-methylene chloride extract of Terminalia glaucescens leaves on mice liver in streptozotocin-induced stress

Aim:

The antioxidant effect of the methanol–methylene chloride extract of Terminalia glaucescens (Combretaceae) leaves was investigated in streptozotocin (STZ)-induced oxidative stress.

Methods:

Oxidative stress was induced in mice by a daily dose of STZ (45 mg/kg body weight i.p.) for five days. From day one, before STZ injection, normal and diabetic-test mice received an oral dose of the extract (100 or 300 mg/kg b.w.) daily. Plasma metabolites, lipid peroxidation, and antioxidant enzymes in the liver were assessed and gain in body weight recorded.

Results:

In normal mice the plant extract reduced food and water intake, blood glucose and LDL-C level and body weight gain, did not affect the lipid peroxidation in the liver, while the antioxidant enzyme activities seemed increased. Blood glucose was decreased (P < 0.05) in normal mice treated with 300 mg/kg extract. Diabetic mice pretreated with 100 mg/kg extract as diabetic control mice (DC) showed significant (P < 0.001) body weight loss, polyphagia and polydipsia, high plasma glucose level, decrease in the liver catalase, peroxidase, and superoxide dismutase activities, and increase in lipid peroxidation. The HDL-C level was lowered (P < 0.05) whereas LDL-C increased. In 300 mg/kg extract-pretreated diabetic mice the extract prevented body weight loss, increase of blood glucose level, lipid peroxidation in liver, food and water intake, and lowering of plasma HDL-C level and liver antioxidants; this extract prevented LDL-C level increase.

Conclusion:

These results indicate that T. glaucescens protects against STZ-induced oxidative stress and could thus explain its traditional use for diabetes and obesity treatment or management.     

Effects of short-term and long-term administration of amiodarone on hepatobiliary function in male rats

Functional, biochemical and histological parameters of hepatotoxicity were assessed in male Sprague-Dawley rats receiving amiodarone (Am) short-term by gavage (5, 50, 150 and 500 mg Am kg-1 day-1, 10 days) or dietary exposure (50 ppm, 1500 ppm, 4-week duration), or by long-term dietary exposure (50 ppm, 8-month duration). Serum enzyme (ALT, AST, ICD) levels and histopathological examination indicated no observable evidence of toxicity among rats of any of the treatment groups. Reduced food intake and reduction in weight gain was observed for rats exposed short-term to 1500 ppm dietary Am. Assessment of hepatobiliary function in treated rats indicated that short-term and long-term dietary exposure to Am resulted in a compromised excretion of readily excretable phenolphthalein glucuronide (PG), although inanition may account for this effect in the 1500 ppm group. Rats receiving Am by gavage exhibited a reduction in biliary excretion of PG, which was not dose-dependent. Distribution of Am and its major metabolite, desethylamiodarone, was similar to previous reports wherein both compounds accumulated in adipose, lung and liver tissue. These data suggest that minor alterations of hepatobiliary function occur in the absence of histological alterations and may preceed biochemical changes, as assessed in this study.     

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.