Neuroprotective effect of preadministration with Ganoderma lucidum spore on rat hippocampus

The aim of this study was to investigate if preadministration with Ganoderma lucidum spore (GLS) could (1) alleviate oxidative stress and mitochondrial dysfunction in rat hippocampus of intracerebroventricular (ICV) injection of streptozotocin (STZ), (2) protect neurons from apoptosis, and (3) improve cognitive dysfunction. Three groups of Sprague–Dawley rats were preadministrated with GLS at doses of 2.0, 4.0 and 8.0 g/kg, respectively, for 3 weeks before the ICV STZ injury. Thereafter the rats were operated with ICV STZ (1.5 mg/kg) bilaterally on days 1 and 3. The behavioral alterations, oxidative stress indexes, ATP, cytochrome oxidase (CytOx), and histopathology of hippocampal neurons were studied. The results showed that ICV STZ model rats exhibited a significant increase of malondialdehyde (MDA), a significant decrease of glutathione reductase (GR), reduced glutathione (GSH), ATP and CytOx, accompanied with marked impairments in spatial learning and memory, and severe damage of hippocampal neuron. In conclusion, preadministration with GLS at dose of 8.0 g/kg in ICV STZ rats significantly reversed these abnormalities. In conclusion, preadministration with GLS might protect hippocampus from oxidative impairment and energy metabolism disturbance of ICV STZ. This may also provide useful information for future research on the pathogenesis and prevention of Alzheimer's disease (AD).     

Protective effects of aqueous extract of Artemisia campestris against puffer fish Lagocephalus lagocephalus extract-induced oxidative damage in rats

The aerial parts of Artemisia campestris are often used in Tunisian poisoning cases and are known to possess significant antioxidant activities. The objective of this study is to evaluate the protective effects of an aqueous extract (5 g/l) of A. campestris leaves and stems (AE), on oxidative damages induced by liver extract (LT) from poisonous fish Lagocephalus lagocephalus in wistar rats. AE was found to contain large amounts of K⁺, Na⁺, Ca⁺⁺ and significant antioxidant capacities highlighted by high level of polyphenols and scavenging activities for DPPH and superoxide anion.LT-injected rats (1 ml/100 g body wt) for 10 days showed (1) a reduced appetite and diarrhea resulting in a lower growth rate than controls, (2) a decrease in serum ALT and AST activities suggesting liver functional disorders, (3) an increase of serum urea and creatinine and reduced serum sodium and potassium concentrations highlighting renal insufficiency and (4) an oxidative stress as evidenced by the raise of TBARS and the inhibition of SOD, CAT and GSH-Px activities in liver, kidney and brain tissuesAbsorption of AE as a drink, for 20 days (10 pre-treatment days+10 experiment days) did not lead significant change of studied parameters but prevented all the disorders induced by LT.     

Loss of motoneurons in the ventral compartment of the rat hypoglossal nucleus following early postnatal exposure to alcohol

Perinatal alcohol exposure (AE) has multiple detrimental effects on cognitive and various behavioral outcomes, but little is known about its impact on the autonomic functions. In a rat model of fetal alcohol spectrum disorders (FASD), we investigated neurochemical and neuroanatomical alterations in two brainstem nuclei, the hypoglossal nucleus (XIIn) and the dorsal nucleus of the vagus nerve (Xdn).One group of male Sprague–Dawley rats (n = 6) received 2.625 g/kg ethanol intragastrically twice daily on postnatal days (PD) 4–9, a period equivalent to the third trimester of human pregnancy, and another group (n = 6) was sham-intubated. On PD 18–19, the rats were perfused and medullary sections were immunohistochemically processed for choline acetyltransferase (ChAT) or two aminergic receptors that mediate excitatory drive to motoneurons, α₁-adrenergic (α₁-R) and serotonin 2A (5-HT_2A-R), and c-Fos.Based on ChAT labeling, AE rats had reduced numbers of motoneurons in the ventral XIIn (XIIn-v; 35.4 ± 1.3 motoneurons per side and section vs. 40.0 ± 1.2, p = 0.022), but not in the dorsal XIIn or Xdn. Consistent with ChAT data, both the numbers of α₁-R-labeled motoneurons in the XIIn-v and the area of the XIIn-v measured using 5-HT_2A-R staining were significantly smaller in AE rats (19.7 ± 1.5 vs. 25.0 ± 1.4, p = 0.031 and 0.063 mm² ±0.002 vs. 0.074 ± 0.002, p = 0.002, respectively). Concurrently, both 5-HT_2A-R and c-Fos staining tended to be higher in AE rats, suggesting an increased activation.Thus, postnatal AE causes motoneuronal loss in the XIIn-v. This may compromise upper airway control and contribute to increased risk of upper airway obstructions and sudden infant death in FASD victims.     

Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver,kidney, pancreas and eye lens in rats

The beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) has been explored against hyperglycemia associated secondary complications in streptozotocin induced diabetic rat model. The experimental groups consist of normal control (NC), diabetic control (DC), DC + metformin 100 mg kg⁻¹ bwd, DC + SCE 250 and DC + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase, alanine aminotransferase, albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers like malondialdehyde, protein carbonyls compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited 46.28% of glucose lowering effect and decreased HOMA-IR (2.47), % HbA1c (6.61), lens AR activity (15.99%), and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug.     

A therapeutic approach to treat cardiovascular dysfunction of diabetes

Diabetes greatly increases risk of cardiovascular dysfunction and interruptions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) have been shown to reduce the risk by alteration in extracellular matrix. We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin (through its COX and tPA inhibitory action) and this combination can reduce cardiovascular dysfunction of diabetes. Four weeks after diabetes induction (streptozotocin, 55 mg/kg, i.p.), rats were treated with minocycline (50 mg/kg, p.o.), aspirin (50 mg/kg, p.o.), or minocycline (50 mg/kg, p.o.) plus aspirin (50 mg/kg, p.o.) for a period of next four weeks. At the end of eighth week arterial pressure, heart rate and left ventricular pressure were recorded. Contractile response to phenylephrine (10^?5 M) and relaxation responses to acetylcholine (10^?9–10^?4 M) were obtained from aortic rings of diabetic rats. Gel zymography was performed to evaluate MMP-2 and MMP-9 levels. Heart rate, mean arterial pressure, dp/dt_max and dp/dt_min were found significantly decreased in STZ diabetic rats when compared with normoglycemic group. Treatment with combination of minocycline and aspirin significantly ameliorate these compared to vehicle treated diabetic group. Endothelium-dependent relaxation responses induced by acetylcholine were decreased in diabetic rats and significantly higher in combination treated group. Collagen, MMP-2 and MMP-9 levels were significantly decreased in combined treated group when compared with diabetic control. Present study revealed that aspirin potentate minocycline induced MMP-2 and MMP-9 inhibition to ameliorate cardiovascular dysfunction of diabetes and this combination can be an approach for the treatment.     

Effect of short term treatment of L-carnitine on tissue ACE activity in streptozotocin-induced diabetic rats

Diabetes is commonly related to the both microvascular as well as macrovascular complications. It appears that both metabolic and hemodynamic factors interact to create these problems.In this study the effects of orally administered L-carnitine, a natural amino acid, on ACE activity in streptozotocin (STZ)-induced diabetic rats were investigated. Streptozotocin (60 mg/kg body weight) was given intraperitoneally. Fifty male Sprague–Dawley rats were divided into four groups: untreated normal (C), L-carnitine treated normal (CT), untreated diabetics (D), L-carnitine-treated diabetics (DT). CT and DT received daily L-carnitine 1 g/kg orally for 3 weeks after inducing diabetes.The ACE activities in aorta, heart and kidney homogenates was measured at the end of 3 weeks. They were significantly increased in D compared to C group (P < 0.05) and significantly decreased in aorta, heart and kidney in DT compared to D group.In conclusion, L-carnitine can reduce tissue ACE activity in aorta, heart and kidney in streptozotocin diabetic rats, which may be due to higher NO production.     

Protective effects of epigallocatechin gallate (EGCG) on streptozotocin-induced diabetic nephropathy in mice

There is increasing evidence suggesting that antioxidants in green tea extracts may protect kidneys on the progression of end-stage renal disease. We investigated the protective impacts of (−)-epigallocatechin 3-O-gallate (EGCG) against streptozotocin (STZ)-induced diabetic nephropathy in mice. The mice were divided into 5 groups (n = 10 per group): control (saline, i.p.), STZ (200 mg/kg, i.p.), EGCG50 (50 mg/kg, S.Q.), EGCG100 (100 mg/kg, S.Q.), and EGCG200 (200 mg/kg, S.Q.). Animals were sacrificed at scheduled times after EGCG administration and then quantitative and qualitative analysis were performed. Compared with the control group, the STZ group showed an increase in levels of blood glucose, blood urea nitrogen, creatinine and urine protein amounts with a decrease in body weight. All the above parameters were significantly reversed with EGCG treatment, especially in the EGCG100 group. After STZ injection, there was a mesangial proliferation with increased renal osteopontin accumulation and its protein expression in the glomeruli and the proximal tubules. Mice kidneys after EGCG-treatment showed a reduced expression of above parameters and relatively improved histopathological findings. These results indicated that EGCG 100 mg/kg might provide an effective protection against STZ-induced diabetic nephropathy in mice by osteopontin suppression.     

Attenuation of cyclophosphamide-induced neurotoxicity in rat by yellow dye extract from root of Brimstone tree (Morinda lucida)

Cyclophosphamide is an anticancer and immunosuppressant drug that induces reactive oxygen species (ROS) production, so causing malondialdehyde (MDA) production, which is toxic to cells. This study therefore sought to assess the antioxidant and the protective effect of dietary inclusion (0.5 and 1.0%) of yellow dye from root of Brimstone tree (used to enhance the sensory quality of foods and in folk medicine) on cyclophosphamide-induced oxidative stress in brain. Wistar strain albino rats were placed on diet containing 0.5 and 1.0% yellow dye preparation from root of Brimstone tree for 14 days. Intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 h before the termination of the experiment caused a significant (P < 0.05) increase in the brain malondialdehyde (MDA) content (147.2%) and serum activities of aspartate aminotransferase (AST) (21.7 UI/l), alanine amino-transferase (ALT) (29.6 UI/l), alkaline phosphatase (43.8UI/l) and total bilirubin (1.7 mg/dl). However, there was a significant decrease (P < 0.05) in the MDA of content of the brain and serum enzyme activities, in those rats fed diet containing the yellow dye in a dose dependent manner. The inhibition of oxidative stress in brain and serum enzymes and metabolites by the dye could be attributed to its high total phenol content and antioxidant activity as typified by its reducing power, free-radical scavenging ability, Fe(II) chelating ability and inhibition of lipid peroxidation. Therefore, dietary inclusion of the yellow dye from root of Brimstone tree could prevent cyclophosphamide-induced oxidative stress in brain and the associated toxicity to the liver.     

Low dose of 2,3,7,8 tetrachlorodibenzo-p-dioxin induces testicular oxidative stress in adult rats under the influence of corticosterone

2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes testicular toxicity by increasing the production of reactive oxygen species (ROS). Glucocorticoids have been reported to influence TCDD action in vitro. Stress, characterized by increased glucocorticoid levels, has been found to suppress the testicular function. The present experiments were set up to analyse the effects of a low dose of TCDD on the rat testis under the influence of increased corticosterone levels. TCDD (1 ng/kg b.w./day) and corticosterone (3 mg/kg b.w./day) were administered alone or together to adult male rats for 15 days. Corticosterone administration raised the levels of serum corticosterone and decreased the levels of serum testosterone significantly. In the testicular mitochondrial- and microsomal-rich fractions, corticosterone administration increased the levels of lipid peroxidation and hydrogen peroxide and decreased the activities of antioxidant enzymes like superoxide dismutase and catalase significantly. TCDD administration to rats treated with corticosterone decreased the levels of serum testosterone as compared to rats treated with corticosterone alone. The levels of lipid peroxidation and hydrogen peroxide increased and the activities of superoxide dismutase and catalase were decreased significantly in mitochondrial- and microsomal fractions of the testis of treated rats as compared to those treated with corticosterone alone. It is concluded that stress may enhance the effects of TCDD on the testis.     

Antihyperlipidemic activity of Cassia auriculata flowers in triton WR 1339 induced hyperlipidemic rats

The flower extract of Cassia auriculata, herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of C. auriculata flower on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intravenous (iv) injection of Triton WR 1339 (300 mg/kg b.w.) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of C. auriculata flowers (Et-CAF) (150, 300, 450 mg/kg b.w./day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analysed at three different time intervals for lipid profile, lipid peroxidation products, antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, lovastatin (10 mg/kg/b.w.). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-CAF treatment or standard drug lovastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-CAF treated rats. Pronounced changes were observed at 450 mg/kg b.w. of Et-CAF for 2 weeks and it was comparable to the standard drug lovastatin. The current study provides a strong evidence that Et-CAF has a beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.     

Synaptic degradation of cardiac autonomic nerves in streptozotocin-induced diabetic rats

Background: Cardiac autonomic neuropathy (CAN) is a common complication in type I diabetes mellitus (DM). Nevertheless, the relationship between functional and structural disturbances of cardiac autonomic nerves remains unclear. Methods and results: To clarify this relationship, we studied heart rate variability (HRV) and ultrastructural changes of cardiac autonomic nerves in streptozotocin (STZ)-induced DM in rats. STZ was injected (65 mg/kg intravenous) into the tail vein of male Wistar rats to destroy β cells in the pancreatic islets. After STZ injection, fasting blood sugar (FBS) increased from baseline values of 75 ± 3 mg/dl up to 328 ± 12 mg/dl within 1 week and it reached up to 353 ± 24 mg/dl within 17 weeks. HR in these rats was decreased within 20 days and low HR was maintained for the observation period. TP and HF power started decreasing 20 days after STZ injection, and this decrease progressed throughout the observation period. The L/H power ratio was decreased 80 days after STZ. Electron microscopic findings indicated a depletion of neurotransmitter vesicles and degradation of parasympathetic nerve endings but not of sympathetic ones in the SA node region of the heart in the early stages of DM. In the late stages of DM, the same region showed degradation of both sympathetic and parasympathetic nerve endings. Conclusion: Synaptic degradation in parasympathetic nerves immediately after the onset of DM, and in sympathetic nerves much later in the development of DM is consistent with functional derangements in cardiac autonomic nerve activities assessed by HRV analysis.     

Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats

This study was designed to investigate the possible protective effect of lycopene against the renal toxic effects of OTA. Male Sprague-Dawley rats (<200 g, n = 6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Histopathological examinations were performed and apoptotic cell death in both cortex and medulla was evaluated by TUNEL assay. Besides, biochemical parameters and activities of renal antioxidant selenoenzymes [glutathione peroxidase 1 (GPx1), thioredoxin reductase (TrxR)], catalase (CAT), superoxide dismutase (SOD); concentrations of total glutathione (GSH), and malondialdehyde (MDA) levels were measured. OTA treatment was found to induce oxidative stress in rat kidney, as evidenced by marked decreases in CAT (35%) activity and GSH levels (44%) as well as increase in SOD activity (22%) vs control group. Furthermore, TUNEL analysis revealed a significant increase in the number of TUNEL-positive cells in cortex (49%) and medulla (75%) in OTA administrated group compared to control (p < 0.05). Lycopene supplementation with OTA increased GPx1 activity and GSH levels, and decreased apoptotic cell death in both cortex and medulla vs. control. The results of this study showed that at least one of the mechanisms underlying the renal toxicity of OTA is oxidative stress and apoptosis is the major form of cell death caused by OTA. Besides, our data indicate that the natural antioxidant lycopene might be partially protective against OTA-induced nephrotoxicity and oxidative stress in rat.     

Leukocyte infiltration in lung,muscle, and liver after limb compression in rats

Muscle crush injury is associated with systemic manifestations known as crush syndrome. A systemic inflammatory response syndrome may be triggered by isolated crush injury. Using myeloperoxidase (MPO) activity and plasma fatty acid composition, we investigated the inflammatory response in distant organs after isolated limb compression in rats. Male Wistar rats were submitted to 1 h of hind limb compression by a latex ribbon. Myeloperoxidase activity was measured in muscle, liver, and lung at progressive times (1, 2 or 4 h) after bandage release. Plasma fatty acid composition was evaluated as an indirect measure of oxidative stress. The liver and hind limb muscles showed a transient increase in MPO activity. Pulmonary MPO activity, otherwise, increased progressively throughout the study and reached statistically significant values at 4 h when compared to all other groups (p < 0.05). Plasma levels of unsaturated fatty acids decreased gradually after decompression (p < 0.05 compared to controls after 4 h). Blunt traumatic muscle compression was associated with rapid and transient muscle and liver inflammatory cell infiltration but otherwise, polymorphonuclear cells showed progressive aggregation in lungs. The plasmatic unsaturated index decreased throughout the 4 h after muscle release. We demonstrated that limb compression was associated with oxidative stress and distant inflammatory responses. Progressive inflammatory cell infiltration in lungs could be related with the delayed systemic adverse responses found after crush injury.     

Antidiabetic,antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice

The present study describes the antidiabetic effect of the flavonoid rich fraction of Pilea microphylla (PM1). HPLC characterization of PM1 revealed the presence of polyphenols viz., chlorogenic acid, rutin, luteolin-7-O-glucoside, isorhoifolin, apigenin-7-O-glucoside, and quercetin. PM1 inhibited dipeptidyl peptidase IV (DPP-IV) in vitro with an IC₅₀ of 520.4 ± 15.4 μg/ml. PM1, at doses of 300, 600 and 900 mg/kg i.p., also produced dose-dependent mean percent reductions of 9.9, 30.6 and 41.0 in glucose excursion (AUC_0–120 min) respectively in lean mice. However, even the highest dose of PM1 did not alter normoglycemic condition. PM1 at dose of 100 mg/kg/day, i.p. for 28 days produced significant (p < 0.05) reduction in body weight, plasma glucose (PG), triglycerides (TG) and total cholesterol (TC) content in high-fat streptozotocin-induced diabetic mice. PM1 also improved oral glucose tolerance significantly (p < 0.05) with mean percentage reduction of 48.0% in glucose excursion (AUC_0–120 min) and significantly (p < 0.05) enhanced the endogenous antioxidant status in mice liver compared to diabetic control. PM1 preserved islet architecture and prevented hypertrophy of hepatocytes as evident from the histopathology of pancreas and liver. PM1 did not show any detectable hematological toxicity at therapeutic doses. In conclusion, PM1 exhibits antidiabetic effect possibly by inhibiting DPP-IV and improving antioxidant levels in high fat diet/streptozotocin (HFD/STZ) diabetic mice.     

The role of oxidative stress and inflammatory response in high-fat diet induced peripheral neuropathy

ObjectiveEarlier studies suggest that high-calorie diet is an important risk factor for neuronal damage resulting from oxidative stress of lipid metabolism. In our experimental study of rats under high-fat diet, oxidative stress markers and axonal degeneration parameters were used to observe the sciatic nerve neuropathy. The aim of this study is to evaluate the pathophysiology of neuropathy induced by high-fat diet.MethodsA total of 14 male rats (Wistar albino) were randomly divided into two experimental groups as follows; control group (n = 7) and the model group (n = 7); while control group was fed with standard diet; where the model group was fed with a high-fat diet for 12 weeks. At the end of 12 weeks, the lipid profile and blood glucose levels, interleukin-1β (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β) levels were studied. Tissue malondialdehyde (MDA), nitric oxide (NO) levels and super-oxide dismutase (SOD), paraoxonase-1 (PON-1) and glutathione peroxidase (GPx) activities were studied. The distal blocks of the left sciatic nerves were evaluated for histomorphological analysis (including mean axon area, axon numbers, nerve fiber diameters, axon diameters, and thickness of myelin sheets).ResultsBody weights, serum glucose and high-density lipoprotein (HDL) levels of rats were found not statistically significantly different compared between the model and the control groups (p > 0.05). Serum cholesterol, triglyceride, TGF-β and TNF-α levels were significantly higher in the model group when compared with the control group (p < 0.05). IL-1 and IL-6 levels were not statistically significantly different compared between the model group and the control group (p > 0.05). The MDA and NO levels and the SOD and GPx activities of the sciatic nerves in model group were statistically significantly higher than the control group (p < 0.05). In addition, the activities of PON-1 were statistically significantly lower in the model group when compared with the control group (p < 0.05). The difference in the total number of myelinated axons between the control group and the model group was not statistically significant (p > 0.05). The nerve fiber diameter and the thickness of the myelin sheet were statistically significantly lower in the model group when compared with the control group (p < 0.05). The axon diameter and area were significantly decreased in the model group when compared with the control group (p < 0.05).ConclusionOur results support that dyslipidemia is an independent risk factor for the development of neuropathy. In addition, we postulated that oxidative stress and inflammatory response may play an important role in the pathogenesis of high-fat diet induced neuropathy.     

Effects of alcohol consumption on biomarkers of oxidative damage to DNA and lipids in ethanol-fed pigs

Chronic alcohol consumption is known to result in tissue injury, particularly in the liver, and is considered a major risk factor for cancers of the upper respiratory tract. Here we assessed the oxidative effects of subchronic ethanol consumption on DNA and lipids by measuring biomarkers 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and malondialdehyde (MDA), respectively. Physiological responses of pigs (n = 4) administered ethanol in drinking water for 39 days were compared with those of water-fed pigs (n = 4). Alcoholisation resulted in serum ethanol concentration of 1.90 g L^?1 and in a moderate but significant increase in alanine aminotransferase activity, an index of liver injury. However, between the alcoholised and control groups there were no significant differences in the levels of 8-oxodG (8-oxodG per 10⁶ 2′deoxyguanosine) from leucocytes (2.52 ± 0.42 Vs 2.39 ± 0.34) or from target organs, liver, cardia and oesophagus. Serum MDA levels were also similar in ethanol-fed pigs (0.33 ± 0.04 μM) and controls (0.28 ± 0.03 μM). Interestingly, levels of 8-oxodG in cardia were positively correlated with those in oesophagus (Spearman correlation coefficient R = 1, P < 0.0001). Our results suggest that alcohol consumption may not cause oxidative damage to DNA and lipids as measured by 8-oxodG and MDA, respectively. The duration of alcoholisation and the potential alcohol-induced nutritional deficiency may be critical determinants of ethanol toxicity. Relevant biomarkers, such as factors involved in sensitization to ethanol-induced oxidative stress are required to better elucidate the relationship between alcohol consumption, oxidative stress and carcinogenesis.     

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: A novel study

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague–Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl₄ treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl₄, were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl₄ in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl₄-induced oxidative damage in rats.     

Oxidative and proteolytic profiles of the right and left heart in a model of cancer-induced cardiac cachexia

Cardiac cachexia is a syndrome that has received increased attention in recent years. Although an association between proteolysis and cardiac cachexia has been proposed, the direct influence of oxidative stress on the process has not been demonstrated. In the present study, the right (RH) and left (LH) hearts (atrium and ventricle of each side of the heart) were collected from rats at the 5th and 10th days after phosphate buffer (control) orWalker-256 solid tumour implantation. Immediately after sacrifice, cachexia was determined in tumour-bearing animals by the formula: [(inicial body weight − final body weight + tumour weight + weight gain of control group)/(initial body weight + body mass gain of control group)] × 100%; RH and LH were stored until use. Oxidative stress and proteolysis were determined in each collected sample. In addition, heart samples were collected from a separate set of animals to determine the thickness of the left and right ventricles. Cachexia values increased over time after tumour implantation from 6.85% at the 5th day to 17.76% at the 10th day. There was no significant difference in LH wet weight and ventricle thickness compared with the control, where as RH wet weight (0.109 ± 0.09 g at the 5th day and 0.093 ± 0.09 g at the 10th day) and thickness (420 ± 16 μm at the 5th day and 279 ± 08 μm at the 10th day) were significantly decreased at both time points when compared with control values (0.153 ± 0.06 g and 607 ± 21 μm, respectively). tert-Butyl-stimulated chemiluminescence analysis revealed a significant increase in the LH and decrease in the RH oxidative stress profiles. Carbonylated proteins increased in the LH (140%, p < 0.05) and RH (100%, p < 0.05) at the 5th day, and significantly decreased in both sides on the 10th day compared to controls. Chemotrypsin-like, caspase-like, and calpain-like activities were evaluated by chemiluminescence, and only calpain-like activity was found to increase at the 5th day in the RH. In the LH, all proteolytic activities systems were decreased when compared with controls. Together, these results demonstrate that oxidative stress appears to play a different role in mass modulation on the LH and RH. The proteolytic systems evaluated herein also appear to have different effects on the responses developed during cardiac cachexia in the two sides of the heart.     

β-Caryophyllene,a natural sesquiterpene,modulates carbohydrate metabolism in streptozotocin-induced diabetic rats

The study was designed to evaluate the antihyperglycemic effects of β-caryophyllene (BCP), a natural sesquiterpene from spices on streptozotocin (STZ) induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (40 mg/kg b.w.) in adult male Wistar rats. Diabetic rats exhibited an increase in glucose and HbA_1c with a significant fall in insulin and hemoglobin levels. Aberrations in carbohydrate metabolic enzymes were noticed in liver, kidney and skeletal muscle of diabetic rats. A fall in liver and skeletal muscle glycogen with alterations in glycogen synthase and phosphorylase activities was also observed. Oral administration of BCP in dose dependent manner and glibenclamide (600 μg/kg b.w.), a standard oral hypoglycemic drug to diabetic rats for 45 days significantly decreased glucose with increased plasma insulin levels and ameliorated the altered activities of carbohydrate metabolic enzymes to near normal. The insulinotropic effect of BCP was supported by immunohistochemical studies. BCP at a dose of 200 mg/kg b.w. exerted significant antidiabetic effects than other two doses (100 and 400 mg/kg b.w.). We conclude that administration of BCP has beneficial effects in glucose homeostasis in diabetic rats.     

Aspartate and glutamate prevents isoproterenol-induced cardiac toxicity by alleviating oxidative stress in rats

The protective effect of aspartate and glutamate in isoproterenol induced myocardial infarction (MI) was investigated in experimental animals. Male albino wistar rats were pretreated with aspartate [100 mg (kg body weight)-1day-1] or glutamate [100 mg (kg body weight)-1day-1] intraperitoneally for a period of 7 days. Following amino acid treatment, MI was induced in rats by subcutaneous injection of isoproterenol [200 mg (kg body weight)-1day-1] for 2 days. After 24 h following the last injection, the animals were sacrificed and the biochemical analysis was carried out. The activities of cardiac marker enzymes (alanine transaminase, aspartate transaminase, lactate dehydrogenase and creatine phosphokinase) were increased significantly (P<0.05) in the serum of MI induced rats as compared to control rats. The levels of glutathione and mitochondrial ATP and the activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase) were decreased whereas lipid peroxides increased significantly (P<0.05) in the heart of MI induced rats as compared to control rats. However, pretreatment with aspartate or glutamate to MI induced rats significantly (P<0.05) reduced the activities of cardiac marker enzymes and increased the activities of antioxidant enzymes as compared to MI induced rats. Aspartate or glutamate pretreatment also increased the levels of glutathione and mitochondrial ATP while decreased the level of lipid peroxides in the cardiac tissue. The overall effects of aspartate and glutamate in reducing the oxidative stress in MI induced rats are similar. There was no significant difference between the control rats and aspartate or glutamate treated control rats. The present study shows that aspartate and glutamate could reduce oxidative stress in MI induced rats.