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.     

Effects of N-methyl-d-aspartate (dizocilpine) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (LY215490) receptor antagonists on the voiding reflex induced by perineal stimulation in the neonatal rat

The present study was undertaken to examine the role of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-d-aspartate glutamate receptors in the regulation of voiding reflexes induced by perineal stimulation in the neonatal rat. Four-, six- and 10-day-old awake rats were used in the experiments and perineal stimulation was applied using the tip of a 1-ml syringe to evoke voiding. Voided volume and residual volume were measured. In 10-day-old rats, LY215490 (3–10 mg/kg, i.p.), a competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist, significantly inhibited reflex voiding, increasing the residual volume 34–53-fold. A 3 mg/kg dose decreased the urine release by 55%, whereas 10 mg/kg totally suppressed the voiding reflex induced by the perineal stimulation. LY215490 (10 mg/kg, i.p.) produced similar effects in four- and six-day-old rats. Dizocilpine (1–3 mg/kg, i.p.), a non-competitive N-methyl-d-aspartate receptor antagonist, also significantly decreased the urine release (62–82%) and increased residual volume (180–230-fold). Combined administration of LY215490 (1 mg/kg, i.p.) and dizocilpine (0.3 mg/kg, i.p.) to 10-day-old rats, in doses that individually had no effect on perineal stimulation-evoked voiding, depressed voided volume by 65%.These results indicate that, in neonatal rats, glutamatergic transmission in the spinal cord has an essential role in reflex micturition induced by perineal stimulation, and that facilitatory interactions between α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and N-methyl-d-aspartate glutamatergic mechanisms are important for voiding, as noted previously in adult rats.     

Regulation of cardiac oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with aqueous extract of Pimpinella tirupatiensis tuberous root

Plants with antidiabetic activities provide important source for the development of new drugs in the management of diabetes mellitus. The main aim of this study was to evaluate the protective effect of aqueous extract (AE) of Pimpinella tirupatiensis (Pt) tuberous root on cardiac oxidative stress and lipid peroxidation (LPO) in non-diabetic and streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar rats by a single administration of STZ (40 mg/kg intraperitoneal (i.p). AE (750 mg/kg/b.w./day) and glibenclamide (GLB) (20 mg/kg/b.w./day) were administrated orally by intra oral gastric tube for 30 days. After 4 weeks of hyperglycaemia the enzymatic and non-enzymatic factors were measured in cardiac tissue of diabetic and control groups. Xanthine oxidase activity (XOD), Uric acid (UA) and malondialdehyde (MDA) content were significantly (p < 0.01) elevated by 48, 48 and 50% respectively and the contents of glutathione (GSH), ascorbic acid (AA) were significantly (p < 0.01) diminished by 45 and 42% respectively in diabetic rats when compared to normal. Treatment with AE and GLB normalized the content of UA, GSH, AA, MDA and the activity of XOD. No significant changes were observed in control rats treated with AE. This data suggests that hyperglycemia induces oxidative stress in the heart, but the oxidative stress defense mechanisms in the heart tissue are fairly efficacious against oxidative injury by the treatment with AE and GLB. The present study reveals that AE may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus.     

Comparison of the protective effects of various antiulcer agents alone or in combination on indomethacin-induced gastric ulcers in rats

The aim of this study which was structured with the objective of determination of the optimum protective therapy against the long term NSAID therapy-induced ulcers was to compare the gastro-protective effects of various antiulcer drugs (ranitidine, omeprazole, bismuth and misoprostol) alone or in combination with each other in different doses on indomethacin-induced gastric ulcers in rats.In this experimental study the protective effect of misoprostol (100 μg/kg/day and 10 μg/kg/day i.g.), omeprazole (5 mg/kg/day and 1.5 mg/kg/day i.p.), ranitidine (40 mg/kg/day and 10 mg/kg/day i.p.), bismuth (70 mg/kg/day and 15 mg/kg/day i.g.), combinations of misoprostol (10 μg/kg/day i.g.) plus omeprazole (1.5 mg/kg/day i.p.) and misoprostol (10 μg/kg/day i.g.) plus ranitidine (10 mg/kg/day i.p.) are investigated on indomethacin (50 mg/kg/day s.c.) induced gastric ulcers. Half an hour before indomethacin administration, each group received the above treatment regimens for 5 days. After 5-day treatment, the rats were sacrificed and histopathological and hematological examinations were performed. The following regimens were found to be effective in the prevention of indomethacin-induced gastric lesions: 100 μg/kg misoprostol, 10 μg/kg misoprostol, 5 mg/kg omeprazole, combination of 10 μg/kg misoprostol plus 1.5 mg/kg omeprazole and 10 μg/kg misoprostol plus 10 mg/kg ranitidine. The prevention rates achieved by these treatments were 71.4%, 50%, 47.6%, 52.4% and 50%, respectively. As a result of this study, misoprostol and omeprazol were found to be effective in protection against NSAID-induced gastric problems; while, ranitidine and bismuth were not. Also, the combinations of these agents were not found to have additive or synergistic effects.     

Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats

The aim of this study was focused on investigating the possible protective effect of NS against GS-induced nephrotoxicity. Twenty four Wistar-albino rats were divided into four equal groups as follows: control group, GS group (100 mg/kg intraperitoneal – i.p.), NSL+GS group (0.2 ml/kg+100 mg/kg i.p.) and NSH+GS group (0.4 ml/kg+100 mg/kg i.p.). Plasma creatinine and urea levels significantly increased as a result of nephrotoxicity in the GS group. Also, creatinine and urea levels significantly decreased in NSL+GS and NSH+GS groups. In the GS group, plasma MDA and NO levels increased significantly (p<0.05) and erythrocyte SOD and GSH-Px activities decreased significantly (p<0.05) when compared with control group. NS administration with GS injection resulted in significantly decreased MDA and NO generation and increased SOD and GSH-Px activities when compared with GS group. Proximal tubular necrosis, vacuolation, desquamation and degeneration in epithelial cells of the proximal tubules, hyaline casts in tubular lumen, mononuclear cell infiltration, glomerular and basement membrane alterations were histopathologically detected in the kidneys of the GS group. Co-treatments with NS (low and high dose) considerably decreased the renal damage when compared with the GS group. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GS both in the biochemical and histopathological parameters.     

Immunohistochemical and histological evaluations of cyclophosphamide-induced acute cardiotoxicity in wistar rats: The role of turmeric extract (curcuma)

Chemotherapy-induced cardiac derangement is a major concern in health sector. Cyclophosphamide as a chemotherapeutic agent induces acute cardiotoxicity through its toxic metabolite, acrolein. This study evaluated the effect of ethanol extract of turmeric on cyclophosphamide-induced acute cardiotoxicity in Wistar rats. Thirty-five healthy Wistar rats, weighing 200–250 g were randomly assigned into 7 groups (Groups A, B, C, D, E, F and G) N = 5. Group A was the control, group B was negative control, and group C was administered 200 mg/kg of turmeric extract (orally) only. While groups B, D, E, F and G were all administered 100 mg/kg cyclophosphamide (i.p) for 10 days. Groups D and E were administered 100 mg/kg and 200 mg/kg of turmeric extract (orally) respectively for 72 hours before cyclophosphamide administration. Groups F and G were concomitantly administered 100 mg/kg cyclophosphamide (i.p) with doses of 100 mg/kg and 200 mg/kg of turmeric extract (orally) respectively. The rats were sacrificed under ketamine anesthesia (30 mg/kg i.m). The left ventricle of the heart was excised. One-way ANOVA was used to analyze data. Results revealed that there was statistically significant (P < 0.05) difference in body weight change, CK–MB, and LDH across all experimental groups; which were significantly lower in cyclophosphamide group. Histology and Immunohistochemistry revealed that there were morphological alterations in the myocardium of the left ventricle in group B while turmeric extract ameliorated cyclophosphamide-induced damage in the myocardium in other experimental groups. In conclusion, cyclophosphamide-induced myocardial alterations were significantly ameliorated through administration of ethanol extract of turmeric.     

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.     

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.     

Pyruvate attenuates cardiac dysfunction and oxidative stress in isoproterenol-induced cardiotoxicity

Pyruvate, a potent endogenous antioxidant and an important metabolic fuel is essential for the cardiac function and tissue defense mechanism. The present study was evaluated to investigate whether pyruvate attenuates the development of cardiotoxicity in isoproterenol (ISO)-induced myocardial infarction by assessing hemodynamic, biochemical and histopathological parameters. Subcutaneous injection of ISO (85 mg/kg) administered for 2 days at an interval of 24 h was used for induction of cardiotoxicity. ISO administration significantly decreased arterial pressure indices, heart rate, contractility {(+)LVdP/dt} and relaxation {(?)LVdP/dt} and increased left ventricular end-diastolic pressure. In addition, a significant reduction in activities of myocardial creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels along with increase in thiobarbituric acid reactive substances were also observed following ISO administration. However, pretreatment with pyruvate (0.25, 0.5 and 1.0 g/kg, p.o.) favorably modulated all most every studied parameters in ISO-induced myocardial injury. Furthermore, protective effect of pyruvate was confirmed by histopathological studies. Rats pretreated only with pyruvate did not produce significant change in hemodynamic, biochemical and histopathological parameters. Pyruvate at 0.50 and 1.0 g/kg doses was found to exert optimal cardioprotective effect against ISO-induced myocardial infarction. The results of our study suggest that pyruvate possessing antioxidant activity has a significant cardioprotective effect against ISO-induced myocardial injury.     

Crocus sativus L. (saffron) attenuates isoproterenol-induced myocardial injury via preserving cardiac functions and strengthening antioxidant defense system

Saffron (dried stigmas of Crocus sativus L.), a naturally derived plant product, has long been used as a traditional ancient medicine against various human diseases. The aim of the series of experiments was to systematically determine whether saffron exerts cardioprotection in isoproterenol-induced myocardial damage. Male Wistar rats (150–175 g) were divided into five groups: control, isoproterenol (ISO) and three saffron (200, 400 and 800 mg/kg) treatment groups. Aqueous extract of saffron or vehicle was administered orally to rats for four weeks. On days 28 and 29, the animals in ISO and saffron treatment groups were administered ISO (85 mg/kg, s.c.) at an interval of 24 h. On day 30, after recording hemodynamics and left ventricular functions, animals were sacrificed for biochemical, histopathological and electromicroscopical examinations. Isoproterenol challenged animals showed depressed hemodynamics and left ventricular functions as evident by decreased left ventricular rate of peak positive and negative pressure change and elevated left ventricular end-diastolic pressure. Structural and ultrastructural studies further confirmed the damage which was reconfirmed by increased thiobarbituric acid reactive substances (p < 0.001) and decreased creatine kinase-MB and lactate dehydrogenase (p < 0.001). In addition, significant reduction in superoxide dismutase and catalase (p < 0.001) was observed in ISO group. Our results suggested that saffron at all the doses exerted significant cardioprotective effect by preserving hemodynamics and left ventricular functions, maintaining structural integrity and augmenting antioxidant status. Among the different doses used, saffron at 400 mg/kg dose exhibited maximum protective effects which could be due to maintenance of the redox status of the cell reinforcing its role as an antioxidant.     

The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats

This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl₄) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200–250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl₄ (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl₄ as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 μg/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 μg/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl₄. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl₄ induced acute hepatic damage.     

Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats

Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM₁₀ coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m³, 12.5 mg/m³, and 25 mg/m³), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m³, 12.5 mg/m³, and 25 mg/m³). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p > 0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p > 0.05), but there was a significant difference in MUC5AC expression (p < 0.05). We concluded that subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar reactive hyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats.     

Introduction of trifluoromethyl group into diphenyl diselenide molecule alters its toxicity and protective effect against damage induced by 2-nitropropane in rats

This study was undertaken to investigate if the introduction of trifluoromethyl (F₃C) group into diphenyl diselenide (PhSe)₂ molecule causes acute toxicity in rats. It was further examined if the presence of F₃C group in (PhSe)₂ molecule alters the protective effect caused by (PhSe)₂ against damage induced by 2-nitropropane (2-NP) in rats. To investigate the potential oral toxicity of (PhSe)₂ and (F₃CPhSe)₂, rats received a single oral application of (PhSe)₂ (7.8–312 mg/kg) or (F₃CPhSe)₂ (11.2–448 mg/kg). Calculated lethal dose (LD₅₀) for (PhSe)₂ and (F₃CPhSe)₂ was estimated to be 312 mg/kg (=1 mmol/kg) and 234 mg/kg (=0.52 mmol/kg), respectively. Oral administration of (PhSe)₂ in rats did not change plasma alanine and aspartate aminotransferase activities (AST and ALT) as well as urea and creatinine levels. The introduction of F₃C group into (PhSe)₂ molecule increased AST activity in plasma of rats. (PhSe)₂ (3.2 mg/kg=10 μmol/kg) and (F₃CPhSe)₂ (4.48 mg/kg=10 μmol/kg) protected ALT, AST and γ-glutamyl transferase (γ-GT) activities against the increase caused by oral administration of 2-NP (120 mg/kg) in rats. (PhSe)₂ and (F₃CPhSe)₂ ameliorated hepatic catalase activity altered by 2-NP in rats. These results indicate that the chemical alteration into (PhSe)₂ molecule introduced toxicity and altered its protective effect against damage induced by 2-NP in rats.     

Effect of quercetin against dichlorvos induced nephrotoxicity in rats

This study was carried out to determine the effect of quercetin against renal injury induced by dichlorvos (DDVP) in rats. Rats were randomly assigned to control, DDVP-treated (7.2 mg/kg bw), three different doses of quercetin-treated (2 mg/kg bw, 10 mg/kg bw, 50 mg/kg bw) and different doses of quercetin plus DDVP-treated groups. DDVP was administered daily to rats through their drinking water, and quercetin was administered by intragastric gavage for 90 days. By the end of the 90th day in the DDVP-treated group, the following indices significantly increased compared with the control (P < 0.01): activities of catalase, glutathione peroxidase and superoxide dismutase; level of malondialdehyde in kidney tissues; serum levels of creatinine and urea nitrogen; and level of β2-microglobulin, level of retinol-conjugated protein, and activity of N-acetyl-β-d-glucosaminidase in urine; by contrast, urine uric acid levels significantly decreased. However, in the quercetin (50 mg/kg bw) plus DDVP group, the aforementioned indices were significantly decreased compared with the DDVP-treated group (P < 0.05), except the urine uric acid levels were significantly increased (P < 0.05). Thus, rat exposure to DDVP caused renal injury, including renal tubular, glomerular filtration, and oxidative stress. These toxic effects were also regulated by high-dose quercetin. Histopathological examination revealed that exposure to DDVP induced extensive cell vacuolar denaturation, but milder histopathological alterations in the kidney tissues of rats co-treated with DDVP and quercetin (50 mg/kg bw) were observed. These results indicated that quercetin at 50 mg/kg bw can partly prevent the kidney injury induced by DDVP.     

Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading

The present study aimed to compare levels of VEGFR2 and MMP-9 among control, epithelial dysplasia (ED) and oral squamous cell carcinoma (OSCC) groups. We analyzed 48 patients with oral leukoplakia (OL), 20 patients with OSCC and 21 patients without OL and OSCC. Immunohistochemistry of VEGFR2 and MMP9 were performed and compared among groups. Analysis of tissue immunolocalization of VEGFR2 and MMP-9 assumed non-parametrical distribution and comparison between groups was performed using the Mann–Whitney and Kruskal–Wallis statistical tests. VEGFR2 and MMP9 immunoexpression appeared to correlate with the degree of dysplasia and was observed to increase in lesions with more severe dysplasia as compared to those with lower degrees of dysplasia. Immunoreactivity of MMP-9 was lower in the OL samples compared to the OSCC samples (p = 0.004). We observed no difference in VEGFR2 protein levels between OL and OSCC samples. A positive correlation was found between VEGFR2 and MMP-9 in OL samples (r = +0.452, p = 0.001), however, no correlation was found in OSCC samples (r = −0.042, p = 0.861). In conclusion, the results of the current study suggest that expression of MMP9 and VEGFR2 is associated with ED grading and MMP9 levels are increased in OSCC.     

Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy

Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague–Dawley rats (n=10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P<0.001). The changes were nearly prevented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetylaspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P<0.01) and MK-801 (P<0.05) still showed significant reduction as compared with sham controls.Thus we conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides a better neuroprotective effect than MK-801. With a better therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application.     

Kenaf seed supercritical fluid extract reduces aberrant crypt foci formation in azoxymethane-induced rats

Kenaf (Hibiscus cannabinus) a plant of the family Malvaceae, is a valuable fiber plant native to India and Africa. Kenaf seeds contain alpha-linolenic acid, phytosterol such as β-sitosterol, vitamin E and other antioxidants with chemopreventive properties. In the present study we examined the hypothesis that kenaf seed ‘supercritical fluid extract’ (SFE) extract could suppress the early colon carcinogenesis in vivo by virtue of its bioactive compounds. To accomplish this goal, 60 male rats were randomly assigned to 5 groups which were (1) negative control group [not induced with azoxymethane (AOM)]; (2) positive control group (induced with AOM but received no treatment); (3) group treated with 500 mg/kg kenaf seed SFE extract; (4) group treated with 1000 mg/kg kenaf seed SFE extract; (5) group treated with 1500 mg/kg kenaf seed SFE extract. At 7 weeks of age, all rats except the negative control group received 15 mg/kg of AOM injection subcutaneously once a week for 2 weeks. Rats were euthanized at 13 weeks of the experiment. Number of ACF (mean ± SD) ranged from 84.4 ± 4.43 to 179.5 ± 12.78 in group 2, 3, 4, 5. ACF reductions compared with the untreated group were 45.3, 51.4 and 53.1% in rats fed with 500, 1000 and 1500 mg/kg body weight, respectively. There were no significant differences in weight gain among groups. Our finding indicates that kenaf seed SFE extract reduced AOM-induced ACF in Sprague–Dawley male rats.     

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.     

Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats

The hepatoprotective, curative and anti-oxidant properties of aqueous extract of Hybanthus enneaspermus (Violaceae) used against CCl4-induced liver damage in rats were investigated in the present study. Liver damage was induced by CCl4 (1 ml/kg i.p.), and silymarin was used as a standard drug to compare hepatoprotective, curative and antioxidant effects of the extract. Rats were treated with aqueous extract of H. enneaspermus at a dose of either 200 or 400 mg/kg after division into pre-treatment (once daily for 14 days before CCl4 intoxication) and post-treatment (2, 6, 24 and 48 h after CCl4 intoxication) groups. Pre-treatment and post-treatment with aqueous extract of H. enneaspermus showed significant hepatoprotection by reducing the aspartate transaminase, alanine transaminase, and alkaline phosphatase enzymatic activities and total bilirubin levels which had been raised by CCl4 administration. Pre- and post-treatment with aqueous extract significantly decreased hepatic lipid peroxidation as well as producing a corresponding increase in tissue total thiols. Post-treatment with aqueous extract improved ceruloplasmin levels. The histopathological examination of rat liver sections treated with aqueous extract confirms the serum biochemical observations. The present study results demonstrate the protective, curative and anti-oxidant effects of H. enneaspermus aqueous extract used against CCl4-induced hepatotoxicity in rats, and suggest a potential therapeutic use of H. enneaspermus as an alternative for patients with acute liver diseases.     

Hepatic metabolism of ibuprofen in rats under acute hypobaric hypoxia

Hypobaric hypoxia induced at high altitude causes a subnormal oxygen concentration in cells which affects the drug metabolic and pharmacokinetic (PK) capacity of the body. The metabolism and PK of drugs like ibuprofen may be impaired under hypoxia and may require a different than usual therapeutic dose regimen to ensure safe therapy. The present investigation was undertaken to evaluate the effect of acute hypobaric hypoxia (AHH) on hepatic metabolism and PK of ibuprofen in rats. Animals were exposed to simulated altitude of 7620 m (～25,000 ft) for AHH exposure (6 and 24 h) in a decompression chamber and were administrated with single dose of ibuprofen (80 mg/kg body weight, p.o.). The results showed that GST activity was significantly reduced at 6 h (15%) and 24 h (23%) (p < 0.05) in hypoxic group as compared to normoxic. A significant increase by 20–24% (p < 0.05) in AST level was observed after AHH exposure. LDH activity also exhibited significant increase (p < 0.05) after 24 h of AHH. A significant down-regulated CYP2C9 level and mild histopathological changes were observed after 24 h of AHH. Furthermore, PK variables viz. elimination half-life (T½) and mean residence time (MRT) of ibuprofen exhibited significant increase by 42% and 51% (p < 0.05) respectively after 24 h of AHH. Thus, results suggest that AHH exposure of 24 h significantly affects phase II conjugation pathway, CYP2C9 level, AST level, liver histology and PK parameters. This asserts that AHH can impair disposition of ibuprofen however, it requires further investigation under chronic hypobaric hypoxic conditions.