Tissue Thiobarbituric Acid Reactive Substances Research Articles

English

BACKGROUND Diabetic nephropathy (DN) is one of the commonest causes for end stage renal disease. Renal accumulation of lipids is one of the pathological finding seen in diabetic nephropathy. Diallyl disulphide (DADS), a principle component of garlic oil, is known for its hypolipidemic properties. Diaceto-dipropyl disulphide (DADPDS) is a structural analogue of DADS, and is more palatable and less toxic to diabetic rats. Hence this animal experiment study was undertaken to compare the hypolipidemic and antioxidant effects of DADS and DADPDS on diabetic rat renal tissue and to evaluate the better disulphide among the two that may be used as adjuvant drug in treating or preventing diabetic nephropathy. METHODS This was an animal experimental comparative study. 24 male albino rats were grouped (6 rats in each group) into normal, diabetic control, DADS and DADPDS treated diabetic rats. Diabetes was induced in albino rats by intraperitoneal injection of alloxan. DADS and DADPDS were fed by gastric intubation for 90 days. After stipulated time, kidneys were dissected out and its total lipids, cholesterol and phospholipid levels were estimated along with tissue thiobarbituric acid reactive substances (TBARS) levels. RESULTS Renal tissue total lipids, cholesterol and phospholipids were significantly decreased in DADS and moderately decreased in DADPDS treated diabetic kidneys, when compared to diabetic control rats. But TBARS levels were significantly decreased in DADPDS rat kidneys compared to DADS treated rat kidneys. CONCLUSIONS In this comparative study, we note that DADS has better lipid-lowering effect on renal tissue of alloxan diabetic rats compared to DADPDS. On the other hand, DADPDS has low renal toxic effects, as indicated by low TBARS levels and improvement in blood glucose levels, when compared to DADS treated diabetic rats. Hence, DADS can be used as an adjuvant drug, only in atherogenic diabetic patients without nephropathy and DADPDS can be used as an adjuvant drug in diabetic nephropathy patients. KEYWORDS Diallyl-Disulphide, Diallyl-Dipropyl Disulphide, Diabetic Nephropathy, Renal Lipids

The potential hepatoprotective effects of lovastatin combined with oral hypoglycemic agents in streptozotocin-induced diabetes in rats

Aims: Epidemiologic studies have shown that individuals with diabetes have a higher risk of hepatic diseases which represent a true clinical problem. The purpose of the present study was to assess the possible modulatory effect of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin on therapeutic efficiency of traditional antidiabetics, as metformin and gliclazide, regarding hepatic complications in streptozotocin (STZ)-induced diabetes in rats.Methods: Animals were divided into seven groups; normal control group, STZ control group (50 mg/kg, i.p., single dose), lovastatin group, metformin group, gliclazide group, lovastatin plus metformin group and lovastatin plus gliclazide group. Serum HMG-CoA reductase, in addition to serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as hepatocyte integrity loss markers, hepatic tissue thiobarbituric acid reactive substances (TBARS), glutathione reduced (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase as oxidative stress markers, as well as serum tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) and hepatic nitric oxide end products (NOx) as inflammatory markers were assessed, coupled with a confirmatory histopathological study.Results: The combined effect of lovastatin with metformin or gliclazide was significantly better than either drug alone regarding serum AST, ALP and TNF-α, and hepatic TBARS, GSH, GST, SOD and NOx levels.Conclusions: Hepatic complications associated with diabetes could be improved by combination of metformin or gliclazide with lovastatin.

Effects of Lipidium sativum seeds extract (Garden cress) on the kidney in sodium nitrite receiving rats

This study was carried out to investigate the modulating effect of Lipidium sativum (LS) seeds aqueous extract consumption against sodium nitrite (SN) that induced the nephrotoxicity in male rats. Rats were divided into four groups. Group 1 (control): without any treatment; group 2: injected with a single dose of SN (50 mg/kg body weight) 24 h prior to decapitation intraperitoneally (i.p.); group 3: given orally 300 mg/kg body weight of LS for four weeks; group 4: treated orally with LS for four weeks, then injected with a single dose of SN, at 24 h prior to decapitation (i.p.) with the same doses. The results showed that, the treatment with sodium nitrite revealed a significantly increase in the levels of sodium, chloride, total calcium, ionized calcium, urea, creatinine and uric acid comparing to the control group. In respect to serum potassium, there is a significant decrease when compared to the control group. Also, the kidney tissue thiobarbituric acid reactive substances (TBARS) were significantly increased. But the superoxide dismutase (SOD), glutathione (GSH) and Catalase (CAT) enzymes were markedly decreased. The pre-treatment with LS before the injection of SN improved the harmful effects of SN caused in the serum levels of the biochemical parameters tested and the concentrations of GSH, SOD, CAT and TBARS in the kidney tissue comparing to SN-treated rats. It could be concluded that Lipidium sativum seeds act as a natural substance for ameliorating the alterations in serum electrolytes, kidney function and oxidative damage induced by sodium nitrite in the kidney tissue.

Ameliorative Effect of Beraprost Sodium on Celecoxib Induced Cardiotoxicity in Rats.

Selective COX-2 inhibitors are most widely used analgesic and anti-inflammatory drugs; however, its maximal use is highly associated with various serious abnormal cardiovascular events. Beraprost sodium (BPS), prostacyclin analogue has been shown to vasodilatory, antiplatelates, anti-inflmmatory, and antioxidant activity. The objective of the present study was to evaluate the effect of BPS on celecoxib cardiotoxicity in rats. Toxicity was induced in male Albino rats (250-280 g) by celecoxib (100 mg/kg/day). BPS (30 μg/kg/day) was administered alone and in combination with celecoxib for 14 days and various biochemicals, hemodynamic, left ventricular, biochemical, and histopathological parameters were studied. Cardiotoxicity of celecoxib was revealed by a significant increase in serum lactate dehydrogenase (LDH),troponin-T (Tn-T),tumor necrosis factor-α (TNF- α), creatine kinase-MB (CK-MB) and systolic blood pressure (SBP), left ventricular end diastolic pressure (LVEDP),LV (dp/dt)max,andLV (dp/dt)min as well as tissue thiobarbituric acid reactive substance (TBARS) and a significant decrease in tissue reduced glutathione (GSH). However, treatment with BPS reversed these alteration in LDH, Tn-T, TNF-α, CK-MB, SBP, LVEDP, LV (dp/dt)max, LV (dp/dt)min, TBARS and GSH levels. The histopathological study in cardiac left ventricle revealed protection of myocardium as manifested reduction of fibrosis by abolition of collagen deposition when celecoxib was combined with beraprost sodium. It could be concluded that beraprost sodium may prove a useful adjunct in patients being prescribed celecoxib.

Influence of alpha-lipoic acid on nicotine-induced lung and liver damage in experimental rats.

Nicotine mediates some of the injurious effects caused by consuming tobacco products. This work aimed at investigating the defensive role of alpha-lipoic acid (ALA) with its known antioxidant and antiinflammatory effect in nicotine-induced lung and liver damage. Rats were arranged into 4 groups: control, nicotine, ALA, and ALA-nicotine groups. Oxidative stress and antioxidant status were determined by assessing thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), and glutathione (GSH) levels in lung and liver. Liver enzymes and lipid profiles were measured and pulmonary and hepatic damage were assessed by histopathological examination. Also, serum levels of transforming growth factor beta 1 (TGF-β1) and vascular cell adhesion molecule 1 (VCAM-1) were determined. The results revealed an increase in TBARS in tissues and a reduction in both SOD and GSH activity in the nicotine-treated rats. Nicotine induced high levels of liver enzymes, TGF-β1, VCAM-1, and dyslipidemia with histopathological changes in the lung and liver. ALA administration along with nicotine attenuated oxidative stress and normalized the SOD and GSH levels, ameliorated dyslipidemia, and improved TGF-β1 and VCAM-1 with better histopathology of the lung and liver. The study data revealed that ALA may be beneficial in alleviating nicotine-induced oxidative stress, dyslipidemia, and both lung and liver damage.

Comparison of Aerobic Preservation by Venous Systemic Oxygen Persufflation or Oxygenated Machine Perfusion of Warm-Ischemia-Damaged Porcine Kidneys

Background/Aim: The global shortage of donor organs for transplantation has necessitated the expansion of the organ pool through increased use of organs from less ideal donors. Venous systemic oxygen persufflation (VSOP) and oxygenated machine perfusion (OMP) have previously demonstrated beneficial results compared to cold storage (CS) in the preservation of warm-ischemia-damaged kidney grafts. The aim of this study was to compare the efficacy of VSOP and OMP for the preservation of warm-ischemia-damaged porcine kidneys using the recently introduced Ecosol preservation solution compared to CS using Ecosol or histidine-tryptophan-ketoglutarate solution (HTK). Materials and Methods: Kidneys from German Landrace pigs (n = 5/group) were retrieved and washed out with either Ecosol or HTK after 45 min of clamping of the renal pedicle. As controls, kidneys without warm ischemia, cold stored for 24 h in HTK, were employed. Following 24 h of preservation by VSOP, OMP, CS-Ecosol, or CS-HTK, renal function and damage were assessed during 1 h using the isolated perfused porcine kidney model. Results: During reperfusion, urine production was significantly higher in the VSOP and OMP groups than in the CS-HTK group; however, only VSOP could demonstrate lower urine protein concentrations and fractional excretion of sodium, which did not differ from the non-warm-ischemia-damaged control group. VSOP, CS-Ecosol, and controls showed better maintenance of the acid-base balance than CS-HTK. Reduced lipid peroxidation, as reflected in postreperfusion tissue thiobarbituric acid-reactive substance levels, was observed in the VSOP group compared to the OMP group, and the VSOP and CS-Ecosol groups had concentrations similar to the controls. The ratio of reduced to oxidized glutathione was higher in the VSOP, OMP, and CS-Ecosol groups than in the CS-HTK group and controls, with a higher ratio in the VSOP than in the OMP group. Conclusion: VSOP was associated with mitigation of oxidative stress in comparison to OMP and CS. Preservation of warm-ischemia-damaged porcine kidneys by VSOP was improved compared to OMP and CS, and was comparable to preservation of non-warm-ischemia-damaged cold-stored kidneys.

Mild alcohol intake exacerbates metabolic syndrome in rodents: a putative role of GSK-3β

Metabolic syndrome is characterized with abdominal obesity, insulin resistance, dyslipidemia and hepatic dysfunction. Glycogen synthase kinase-3β (GSK-3β) expression has been observed in adipose tissues in obese and diabetic humans, and in rodents. The aim of study was to investigate role of GSK-3β in modulation of metabolic alterations in alcoholic fed rats. Male Wistar albino rats (180–220 g) were used. High fat diet (HFD) for 8 weeks and alcohol (2%) from third to eighth week were given. Lithium chloride (LiCl), a GSK-3β inhibitor (60 mg/kg) was used orally from third to eighth week. HFD treatment caused significant (p < 0.05) increase in the percentage of body weight gain, BMI, Lee index, different fat pads, liver weights, serum glucose, leptin, triglyceride, LDL, VLDL, cholesterol, alanine transaminase, aspartate transaminase, tissue thio-barbituric acid reactive substances, nitrate/nitrite and significant decrease in food intake (g), serum HDL and tissue GSH in HFD control rats, as compared to normal control (NC). Administration of alcohol (2%) ad libitum potentiated the effect of normal and HFD, respectively, in NC and HFD control rats, respectively. Administration of LiCl produced significant amelioration in biochemical and pathological changes caused in the form of metabolic syndrome in HFD alone and HFD and alcohol-treated rats. The histological observations also showed similar findings in liver tissue. It may be concluded that inactivation of GSK-3β consequently leads to increased leptin and insulin sensitivity as evidenced by the reversal of alterations caused due to metabolic syndrome in rodents fed with HFD and mild alcohol.

Effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats.

The objective of this study was to show the effects of probiotic supplementation on systemic and intestinal oxidant-antioxidant events in splenectomized rats. Male rats were divided into control (group 1) and splenectomized (group 2) groups, and after splenectomy, some rats were given Lactobacillus delbruckii subsp. bulgaricus (highest amount of extracellular polysaccharides, 211mg/l) for 7days (group 3) or were given the treatment for 7days before and 7days after splenectomy (group 4). The plasma and small intestine tissue thiobarbituric acid reactive substances (TBARS), sulfhydryl group, glutathione, ascorbic acid, and nitric oxide metabolites (NO x ) levels were determined by a spectrophotometer. We found increased TBARS levels in both the plasma and small intestine in the splenectomized rats compared to controls. L. delbruckii subsp. bulgaricus supplementation decreased the TBARS levels in the plasma in the splenectomized rats. In this study, the plasma TBARS and NO x levels were decreased by L. delbruckii subsp. bulgaricus supplementation after or both after and before splenectomy (groups 3 and 4). Together, these data suggest that. L. delbruckii subsp. bulgaricus supplementation is beneficial for decreasing lipid peroxidation and enhancing the antioxidant capacity of systemic and intestinal tissue in splenectomized rats.

Tissue Lipid Peroxidation in Trypanosoma brucei Infection: Testing the Anti-oxidant Property of &lt;i&gt;Scoparia dulcis&lt;/i&gt;

The ability of aqueous extract of Scoparia dulcis to protect tissues of rabbits against Trypanosoma brucei-induced oxidative damage was investigated in this study. Fifteen New Zealand White rabbits divided into 3 groups of 5 animals each were used for the study. Animals in group 1 served as controls while those in groups 2 and 3 were inoculated with Trypanosoma brucei. In addition, animals in group 3 received aqueous extract of Scoparia dulcis at a daily dose of 200mg/Kg administered orally. Results obtained show that infection of rabbits with T. brucei resulted in a significant increase in oxidative stress as measured by tissue Thiobarbituric Acid Reactive Substances (TBARS) in the liver and kidney, but not in the heart of infected animals. Whereas both superoxide dismutase (SOD) and catalase were significantly reduced in the liver and kidney 28 days post-inoculation; the decrease in SOD activity in the heart was accompanied by an increase in catalase activity in that tissue. Treatment with S. dulcis at a daily oral dose of 200mg/Kg body weight resulted in a significant protection against the trypanosome-induced oxidative stress, with a significant reduction in the level of TBARS and an improvement in both SOD and catalase levels. Key words : Trypanosoma brucei, Scoparia dulcis, Lipid peroxidation, Catalase, Superoxide dismutase

Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats

Despite the developments in modern medicine, acute renal injury is still a challenging and common health problem. It is well known that ischaemia and reperfusion takes place in pathological mechanisms. Efforts to clarify the pathophysiology and interventions to improve outcomes are essential. Our study aimed to investigate whether the prophylactic use of paricalcitol is beneficial in renal ischaemia/reperfusion (I/R) injury. Twenty-four Wistar albino rats were assigned randomly to four groups. Right nephrectomies were performed at the time of renal arterial clamping. Sham surgery was performed on the rats in group 1. For the rats in group 2, the left renal artery was clamped for 45 minutes. The rats in group 3 received paricalcitol for seven days (0.2μg/kg/day); following this, a right nephrectomy and left renal arterial clamping were not performed. The rats in group 4 received paricalcitol for seven days (0.2μg/kg/day); following this, a right nephrectomy and left renal arterial clamping for 45 minutes were performed. Tissue thiobarbituric acid reactive substances (TBARS), superoxide dismutase, sulfhydryl groups as well as nitric oxide metabolites, serum urea and creatinine levels were measured for all four groups. In group 4, there were some improvements in terms of TBARS, nitrite, nitrate, superoxide dismutase and creatinine levels. In the histopathological evaluation, paricalcitol therapy improved tubular necrosis and medullar congestion but there was no significant difference in terms of tubular cell swelling, cellular vacuolisation or general damage. Immunohistopathological examination revealed lower scores for vascular endothelial growth factor in the group 4 rats than in group 2. Paricalcitol therapy improved renal I/R injury in terms of serum and histopathological parameters. These potential beneficial effects need to be further investigated.

Markers of lipid peroxidation and α‐tocopherol levels in the blood and neoplastic tissue of dogs with malignant mammary gland tumors

Excess reactive oxygen species due to oxidative stress and the ensuing lipid peroxidation are believed to be involved in mammary gland tumor (MGT) pathogenesis. The purpose of this study was to evaluate the extent of lipid peroxidation as evidenced by thiobarbituric acid-reactive substances (TBARS) formation, and the concentration of α-tocopherol as an inhibitor of lipid peroxidation, in blood and neoplastic tissue of dogs with malignant MGT. The correlation between inflammatory cell infiltration score and TBARS or α-tocopherol in MGT was also evaluated. Sixteen intact female dogs with malignant MGT and 12 clinically healthy and age/weight-matched controls were included in the study. In all dogs, serum TBARS, α-tocopherol, total cholesterol, and triglycerides were measured. Tissue TBARS and α-tocopherol levels were determined in 1 cm(3) sized tissue samples collected from MGT and adjacent, ipsilateral, normal mammary gland tissue from the 16 affected dogs. The degree of inflammatory cell tumor infiltration was evaluated histologically. There were no statistically significant differences in serum levels of TBARS, α-tocopherol, total cholesterol, and triglycerides between dogs with and without malignant MGT. TBARS were significantly higher, whereas α-tocopherol was lower in neoplastic tissue when compared with normal mammary gland tissue. There was no correlation between TBARS or α-tocopherol concentration and the inflammatory cell infiltration score in neoplastic tissue. The increased level of TBARS suggests oxidative stress induction in canine malignant MGT. The origin of this phenomenon is not clear, as a potential oxidative burst could not be attributed to inflammatory cells infiltrating the tumors.

Protective effects of magnesium supplementation on metabolic energy derangements in lipopolysaccharide induced cardiotoxicity in mice

Endotoxic shock is a major factor that contributes to morbidity and mortality in critically ill patients in intensive care units. Metabolic derangements and bioenergetic failure are major contributors to sepsis induced cardiotoxicity. The present investigation was directed to estimate the cardioprotective effect of magnesium (Mg), a cofactor in many enzymatic reactions that involve energy creation and utilization, in lipopolysaccharide (LPS)-induced metabolic energy changes in mice. Oral doses of Mg aspartate (20 or 40 mg/kg) were administered once daily for 7 days. Mice were then subjected to a single intraperitoneal injection of LPS (2 mg/kg). Three hours after LPS injection, plasma was separated for determination of creatine kinase-MB activity. Animals were then sacrificed and hearts were separated for estimation of tissue thiobarbituric acid reactive substances, reduced glutathione, lactate, pyruvate, adenine nucleotides,creatine phosphate and cardiac Na+,K+-ATPase activity. Finally, electron microscopic examination was performed to visualize the effect of Mg pretreatment on mitochondrial ultrastructure. The higher dose of Mg was more effective than the lower dose in ameliorating creatine kinase-MB elevation, the state of oxidative stress, lactate accumulation, pyruvate reduction as well as preserving creatine phosphate, adenine nucleotides and Na+,K+-ATPase activity. Moreover, the higher dose of Mg provided a significant cardioprotection against mitochondrial ultrastructure changes. Mg therapy can afford a significant protection against metabolic energy derangements and mitochondrial ultrastructure changes induced by LPS cardiotoxicity. Clinical studies are required to establish the effectiveness of magnesium as an adjunctive therapy in critically ill patients suffering from sepsis.

N-Acetylcysteine prevents doxorubucine-induced cardiotoxicity in rats

This study is designed to observe the effects of N-acetylcysteine (NAC) on doxorubucine-induced cardiac toxicity in rats both histologically and biochemically. Totally 32 rats divided equally into four groups were studied. The first group received only 200 mg/kg NAC intraperitoneal (i.p.) once every 24 h for 5 days (group 1); the second group received 20 mg/kg doxorubucine (DOX) i.p. single dose plus NAC 200 mg/kg i.p. once every 24 h for 5 days (group 2); the third group received DOX 20 mg/kg DOX i.p. single dose (group 3) and the fourth group, which is also the control group, received saline (group 4). Following 24 h of the final dose, blood samples were drawn from a portal vein and heart tissue were obtained. Tissue thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) levels were highest in the DOX group. In the DOX-treated rats, serum TBARS, NO, aspartate transaminase, lactate dehydrogenase and creatine kinase levels were highest when compared with other groups. Except for serum superoxide dismutase levels, all other parameters differed significantly between the DOX plus NAC group and the DOX group. In the DOX plus NAC group, general architecture was preserved better than the DOX group and myofibril loss was minimal compared with the DOX group. NAC demonstrated, both biochemically and histologically, to be effective in the prevention of DOX-induced cardiotoxicity in rat models. Evaluation of NAC's effect on DOX toxicity warrants further clinical trials on cancer patients.

The therapeutic applications of celery oil seed extract on the plasticizer di(2-ethylhexyl) phthalate toxicity

The present study investigated the impact of two doses, 500mg/kg and 1000mg/kg, of di(2-ethylhexyl) phthalate (DEHP) and studied the possible therapeutic dose of celery oil seed extract for 6weeks on some atheroscelerogenic, obesogenic, antioxidant and liver functions in rats. Both doses of DEHP caused over-expression of peroxisome proliferator-activated receptor alpha (PPARα) messenger RNA with significant increase in liver weights, relative liver weights, serum cholesterol (Chol), triglycerides, low-density lipoprotein Chol, liver total lipids, along with an increase in the activities of serum aspartate aminotransferase, alanine aminotransferase, serum endothelin 1 and liver tissue thiobarbituric acid reactive substances (TBARS). Additionally, DEHP administration to rats resulted in significant decrease in final body weights, serum total protein, albumin, liver total protein and serum total nitric oxide. Our study confirmed the role of oral combination of Apium graveolens (celery) oil seed extract at small cumulative doses (50µl/kg for 6weeks) with DEHP in ameliorating the toxicological effects of DEHP, which was revealed in reducing the expression of PPARα, lipid profile, with restoring liver functions, vascular oxidative stress and inhibition of TBARS activity.

Antioxidant Activity and Cardioprotective Effect of a Nonalcoholic Extract ofVaccinium meridionaleSwartz during Ischemia-Reperfusion in Rats

Our objective was to assess the antioxidant properties and the effects against the reperfusion injury of a nonalcoholic extract obtained by fermentation from the Colombian blueberry, mortiño (Vaccinium meridionale Swartz, Ericaceae). Antioxidant properties were assessed by in vitro systems. To examine the postischemic myocardial function, isolated rat hearts were treated 10 min before ischemia and during the first 10 min of reperfusion with the extract. To analyze the participation of nitric oxide (NO), other experiments were performed in the presence of nitric oxide synthase (NOS) inhibition with NG-nitro-L-arginine methyl ester (L-NAME). In cardiac tissue thiobarbituric acid reactive substances (TBARS) concentration, reduced glutathione (GSH) content, endothelial NOS (eNOS), and Akt expression were also measured. The blueberry extract showed higher total phenols and anthocyanins contents, scavenging activity of superoxide radical and systolic and diastolic function was improved, TBARS diminished, GSH was partially preserved, and both NOS and Akt expression increased in hearts treated with the extract. These beneficial effects were lost when eNOS was inhibited. In resume, these data show that the increase of eNOS expression via Akt and the scavenging activity contribute to the cardioprotection afforded by acute treatment with Colombian blueberry extract against ischemia and reperfusion injury.

Protective effects of magnesium supplementation on metabolic energy derangements in lipopolysaccharide-induced cardiotoxicity in mice

Metabolic derangements and bioenergetic failure are major contributors to sepsis-induced multiple organ dysfunctions. Due to the well known role of magnesium (Mg) as a cofactor in many enzymatic reactions that involve energy creation and utilization, the present investigation was directed to estimate the cardioprotective effect of Mg supplementation in lipopolysaccharide (LPS)-induced metabolic energy changes in mice. Oral doses of Mg aspartate (20 or 40mg/kg) were administered once daily for 7day. Mice were then subjected to a single intraperitoneal injection of LPS (2mg/kg). Plasma was separated 3h after LPS injection for determination of creatine kinase-MB activity. Animals were then sacrificed and the hearts were separated for estimation of tissue thiobarbituric acid reactive substances, reduced glutathione, lactate, pyruvate, adenine nucleotides, creatine phosphate and cardiac Na+,K+-ATPase activity. Finally, electron microscopic examination was performed to visualize the protective effects of Mg pretreatment on mitochondrial ultrastructure. In general, the higher dose of Mg was more effective than the lower dose in ameliorating creatine kinase-MB elevation and the state of oxidative stress, lactate accumulation, pyruvate reduction as well as preserving creatine phosphate, adenine nucleotides and Na+,K+-ATPase activity. Moreover, the higher dose of Mg provided a significant cardioprotection against the mitochondrial ultrastructural changes. Mg therapy can afford a significant protection against metabolic energy derangements and mitochondrial ultrastructural changes induced by LPS cardiotoxicity in mice.

Effects of waterborne copper nanoparticles and copper sulphate on rainbow trout, (Oncorhynchus mykiss): Physiology and accumulation

Emerging data suggests that some types of nanoparticles (NPs) are toxic to fish, and given the well-known toxicity of dissolved metals, there are also concerns about whether metal-containing NPs present a similar or different hazard to metal salts. In this study, juvenile rainbow trout were exposed in triplicate to either a control, 20 or 100μgl−1 of either Cu as CuSO4 or Cu-NPs (mean primary particle size, 87±27nm) in a semi-static aqueous exposure regime. Fish were sampled at days 0, 4, and 10 for tissue trace elements, haematology, and biochemistry. By day 4, fish from the 100μgl−1 Cu as CuSO4 treatment showed 85% mortality (treatment subsequently terminated) compared to 14% in the 100μgl−1 Cu-NP exposed fish. Mortality at day 10 was 4, 17, 10, and 19% in the control, 20μgl−1 Cu as CuSO4, 20 and 100μgl−1 Cu-NP treatments, respectively. Copper accumulation was seen in the gills of fish from all Cu treatments, and was statistically significant in both CuSO4 treatments at day 4 and all Cu treatments at day 10 compared to controls. No statistically significant Cu accumulation was seen in the spleen, brain or muscle of fish from any treatment, although an elevation in intestinal Cu was seen in the high Cu-NP treatment throughout. There were some transient changes in haematology and depletion of plasma Na+ that was treatment-related, with some differences between the nano form and metal salt, but Cu-NPs were not overtly haemolytic. A 6-fold decrease in branchial Na+/K+-ATPase activity in all Cu treatments (compared to controls), depletion of plasma and carcass ion concentrations suggest that Cu-NPs are an ionoregulatory toxicant to rainbow trout. Statistically significant decreases in Na+/K+-ATPase activity were also seen in the brains and intestine, and whilst there was no material-type effect in the former, this was only observed in the gut of fish exposed to 100μgl−1 Cu-NPs. There were material-dependent changes in tissue thiobarbituric acid reactive substances (TBARS), and in the gill the Cu-NPs caused a larger (though non-significant compared to control) increase in TBARS than the equivalent metal salt treatment (the latter actually being significantly reduced compared to all other treatments). Overall, these data show that Cu-NPs have similar types of toxic effects to CuSO4, which can occur at lower tissue Cu concentrations than expected for the dissolved metal.

Antinociceptive effect of Butea monosperma on vincristine-induced neuropathic pain model in rats

Neuropathic pain is a chronic neurodegenerative disease. It is well characterized by spontaneous pain, hyperalgesia, hypothesia, dysesthesia and allodynia. The present study was designed to investigate the antinociceptive potential of Butea monosperma on vincristine-induced painful neuropathy in rats. Vincristine was administered for induction of neuropathic pain in experimental animals. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia and allodynia in the hind paw and tail thermal hyperalgesia, respectively, as an index of peripheral and central pain sensation. Tissue thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Microscopically, histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of B. monosperma leaves and pregabalin were administered for 14 consecutive days. Vincristine administration resulted in significant reduction in behavioural (i.e. hyperalgesia and allodynic pain sensation) changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Moreover, significant histological changes were also observed. Pretreatment with B. monosperma significantly attenuated vincristine-induced development of painful behavioural, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. B. monosperma ameliorated vincristine-induced painful neuropathy. It may be due to its potential of antioxidative, neuroprotective and calcium channel inactivation.

Aegle marmelos fruit extract attenuates isoproterenol-induced oxidative stress in rats

Myocardial infarction is a major public health concern and the leading cause of death throughout the world. The present study investigates the ability of Aegle marmelos fruit extract to prevent pathological changes and oxidative stress after isoproterenol induced myocardial infarction in rats. In vitro studies showed that Aegle marmelos fruit extract possesses antioxidant activity. Administration of isoproterenol (85 mg/kg body weight) to rats resulted in significantly elevated plasma transaminases, lactate dehydrogenase and creatine kinase, however, cardiac tissue analyses showed decreased activity of the above enzymes compared to experimental control rats. Further, isoproterenol administration significantly increased plasma and cardiac tissue thiobarbituric acid reactive substances and lowered the activities of cardiac tissue superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and glutathione-S-transferase when compared to control groups. Pretreatment with Aegle marmelos fruit extract at a dose of 150 mg/kg body weight for a period of 45 days significantly prevented the observed alterations. Our data suggest that Aegle marmelos fruit extract exerts its protective effect by decreasing thiobarbituric acid reactive substances and elevating antioxidants status in isoproterenol treated rats. Both biochemical and histopathological results in the isoproterenol-induced myocardial infarction model emphasize the beneficial action of Aegle marmelos fruit extract as a cardioprotective agent.

LOX-1 abrogation reduces cardiac hypertrophy and collagen accumulation following chronic ischemia in the mouse

We hypothesized that lectin-like oxidized LDL receptor-1 (LOX-1) deletion may inhibit oxidative stress signals, reduce collagen accumulation and attenuate cardiac remodeling after chronic ischemia. Activation of LOX-1 plays a significant role in the development of inflammation, apoptosis and collagen signals during acute ischemia. Wild-type and LOX-1 knockout (KO) mice were subjected to occlusion of left coronary artery for 3 weeks. Markers of cardiac hypertrophy, fibrosis-related signals (collagen IV, collagen-1 and fibronectin) and oxidant load (nicotinamide adenine dinucleotide phosphate oxidase expression, activity of mitogen-activated protein kinases and left ventricular (LV) tissue thiobarbituric acid reactive substances) were analyzed. In in vitro experiments, HL-1 cardiomyocytes were transfected with angiotensin II (Ang II) type 1 receptor (AT1R) or type 2 receptor (AT2R) genes to determine their role in the cardiomyocyte hypertrophy. LOX-1 KO mice had 25% improvement in survival over the 3-week period of chronic ischemia. LOX-1 deletion reduced collagen deposition and cardiomyocyte hypertrophy (∼75%) in association with a decrease in oxidant load and AT1R upregulation (all P<0.05). The LOX-1 KO mice hearts exhibited a disintegrin and metalloproteinase 10 (ADAM10) and a disintegrin and metalloproteinase 17 (ADAM17) expression and matrix metalloproteinase 2 activity, and increased AT2R expression (P<0.05). Attenuation of cardiac remodeling was associated with improved cardiac hemodynamics (LV ±dp/dt and cardiac ejection fraction). In vitro studies showed that it is AT1R, and not AT2R overexpression that induces cardiomyocyte hypertrophy. We demonstrate for the first time that LOX-1 deletion reduces oxidative stress and related intracellular signaling, which leads to attenuation of the positive feedback loop involving AT1R and LOX-1. This results in reduced chronic cardiac remodeling.