Protective Effect Of Different Doses Research Articles

Protective Effects of Crocin Against Hepatic Damages in D-galactose Aging Model in Rats.

Aging is a progressive process which is associated with liver dysfunction and it is due to oxidative stress, inflammation, and cell apoptosis. Long-term D-galactose (D-gal) administration is able to develop an aging model in animals. Crocin as a major active ingredient in saffron has shown anti-inflammatory and hepatoprotective effects via its antioxidant capacity. Thus, the aim of the present study was the assessment of crocin effects on hepatic and metabolic disorders induced by D-gal in rats. Aging model was induced in rats by 56-day administration of D-gal (400 mg/kg/day subcutaneously). Protective effects of different doses of crocin (7.5, 15 and 30 mg/kg/day) in concomitant with D-gal administration were evaluated. Malondialdehyde (MDA) and reduced glutathione (GSH) amounts were measured by means of their reaction, respectively, with thiobarbituric acid and 5,5′-Dithiobis (2-nitrobenzoic acid) (DTNB) under a specific condition. Cyclooxygenase-2 (COX-2), β-galactosidase, induced nitric oxide synthase (iNOS), and carboxymethyllysine (CML) levels were determined by western blotting method. Additionally, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured in serum. D-gal administration significantly elevated ALT, AST, ALP levels, which were markedly inhibited by crocin administration. Crocin suppressed the overgeneration of lipid peroxidation products such as MDA. iNOS was elevated by D-gal administration and was returned to the normal extent by crocin. Therefore, Crocin as a powerful antioxidant and radical scavenger, totally exhibited hepatoprotective effects against D-gal-induced toxicity in rats.

Protective effect of different doses of pycnogenol extract against gamma radiation-induced liver damage in rat

Protective effect of different doses of pycnogenol extract against gamma radiation-induced liver damage in rat

Deletion of the LuxR-type regulator VjbR in Brucella canis affects expression of type IV secretion system and bacterial virulence, and the mutant strain confers protection against Brucella canis challenge in mice

Brucella spp. are facultative intracellular pathogens and zoonotic agents which pose a huge threat to human health and animal husbandry. The B. melitensis, B. abortus, and B. suis cause undulant fever and influenza-like symptoms in humans. However, the effects of B. canis have not been extensively studied. The quorum sensing-dependent transcriptional regulator VjbR influences the Brucella virulence in smooth type Brucella strains, such as B. melitensis, B. abortus and rough type Brucella ovis. However, the function of VjbR in the rough-type B. canis is unknown. In the present study, we discovered that deletion of this regulator significantly affected Brucella virulence in macrophage and mice infection models. The expression levels of virB operon and the ftcR gene were significantly altered in the vjbR mutant strain. We further investigated the protective effect of different doses of the vjbR mutant in mice and the results indicated that VjbR conferred protection against the virulent B. canis strain. This study presents the first evidence that the transcriptional regulator VjbR has important function in B. canis. In addition, according to its reduced virulence and the protective immunity it induces in mice, it can be a potential live attenuated vaccine against B. canis.

Evaluation of the protective effects of Ganoderma atrum polysaccharide on acrylamide-induced injury in small intestine tissue of rats.

This research investigated the protective effects of Ganoderma atrum polysaccharide (PSG-1) on acrylamide (AA) induced intestinal injury in rats. Our results showed that PSG-1 pretreatment effectively reduced the levels of malondialdehyde (MDA), but increased the activity of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and the total glutathione (T-GSH), and significantly reduced oxidative stress in AA treated rats. Furthermore, PSG-1 pretreatment down-regulated pro-inflammatory cytokines i.e. interleukin 2 (IL-2), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) and increased the amounts of anti-inflammatory cytokines i.e. interleukin 4 (IL-4) and interleukin 10 (IL-10), significantly reducing an inflammatory response in the intestines of rats. In AA induced intestinal injury, the tissue uric acid (UA) level and alkaline phosphatase (ALP) activity and the serum level of d-lactic acid (d-lactate), nitric oxide (NO) and endothelin-1 (ET-1) decreased significantly after treatment with PSG-1 and N-acetylcysteine (NAC). Histological observations of the small intestine confirmed the protective effects of different doses of PSG-1. These findings suggested that PSG-1 pretreatment could alleviate AA-induced oxidative stress, reduce inflammatory response, and inhibit AA absorption by protecting the intestinal barrier. Therefore, Ganoderma atrum polysaccharide has the potential to be a dietary supplement ingredient that provides protection against AA-induced gut injury.

Effect of Suramin on Renal Proximal Tubular Cells Damage Induced by Cisplatin in Rats (Histological and Immunohistochemical Study).

Background:Renal toxicity is the most common complication of cispaltin therapy that has broad-spectrum antitumor activity against a variety of human solid tumor. Suramin, a Food and Drug Administration-approved old drug is a polysulfonated compound of napthylurea originally designed to treat trypanosomiasis.Aim:The current work aimed to investigate the possible protective effect of different doses of suramin against cisplatin-induced renal proximal tubular cells (RPTCs) damage.Material and Methods:Fifty adult male rats were used and divided into five equal groups. Group I served as a control, group II received suramin alone (10 mg/kg). Groups III, IV and V were administered cisplatin once (5 mg/kg, intraperitoneally) alone or combined with low dosage suramin (5 mg/kg) or high dosage suramin (10 mg/kg) once intravenously respectively.Results:Compared with control rats, cisplatin administration caused proximal tubules damage, RPTCs vacuolation with pyknotic nuclei, loss of brush border and widespread caspase-3 immunostaining. Cisplatin-induced RPTCs toxicity was further confirmed morphometrically (a significantly decreased proximal tubular epithelium height and increased mean number of caspase-3-immunopositive cells). These changes were accompanied by biochemical alteration manifested as a significant increase of blood urea nitrogen and serum creatinine. Simultaneous administration of high-dose but not low-dose suramin to the cisplatin-treated rats improved the deleterious morphological and morphometrical effects on RPTCs and restored the aforementioned biochemical parameters to control values.Conclusion:In conclusion suramin in a dose dependant manner protects RPTCs from damage induced by cisplatin.

Protective effects of resveratrol against X-ray irradiation by regulating antioxidant defense system

Ionizing radiation interacts with biomolecules to produce free radicals, which can damage all components of the cell. The aim of this study was to evaluate the protective effects of different doses of resveratrol against X-ray-induced damage in male rat. The animals were divided into five groups, each composed of six rats: two groups as control groups received saline or ethanol (ethanol in saline, 25%, V/V as a vehicle). Two groups received resveratrol (5 and 10 mg/kg.bwt) for 30 days before X-ray exposure. One group received X-ray. The rats were sacrificed 24 h after the last exposure, blood samples were collected and serum level of malondialdehyde (MDA), total antioxidant capacity (TAC), and the activities of superoxide dismutase (SOD) and catalase (CAT) were measured by spectrophotometric method. X-ray irradiation significantly increased the levels of MDA and decreased TAC as well as SOD activity as compared with control groups. Furthermore, resveratrol pretreatment led to remarkable decrease in MDA concentration and increase in the activities of SOD and CAT as well as TAC compared to those of controls. Our results revealed antioxidant properties of resveratrol and suggest it as a potent radioprotector to ameliorate X-irradiation induced damage in the body.

Effects of ascorbic acid on the expression of p53 and Bcl-2 protein in NIH/3T3 cells exposed to nickel

Objective: To study the protective effect of Ascorbic acid (AA) on the injury of nickel-exposed mouse embryonic fibroblasts (NIH/3T3) . Methods: A model of damage induced by 50 μg/mL nickel refining dust was established to determine the relative survival rate of cells, superoxide dismutase (SOD) , lactate dehydrogenase (LDH) and glutathione peroxidase. (GSH-Px) activity, hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA) content, and p53 (wild-type) , Bcl-2 protein expression. To investigate the protective effect of different doses of ascorbic acid (25, 50, 100 mmol/L) on nickel-refined dust-induced NIH/3T3 cell injury. Results: The study showed that ascorbic acid Ⅲ group can make the NIH/3T3 cell survival rate increased significantly; Apoptosis rate was reduced; The vitality of SOD and GSH-Px increased significantly, and the difference was statistically significant (P<0.05) . At the same time, the level of MDA and H(2)O(2) and the activity of extracellular LDH enzyme were significantly reduced, and the difference was statistically significant (P<0.05) . The results showed that nickel refining dust induced cell damage through up-regulation of p53 protein and down-regulation of Bcl-2 protein expression; ascorbic acid interventions, the expression level of Bcl-2 protein in ascorbic acid II and III groups was higher than that of nickel refining dust group, and the difference was statistically significant (P<0.05); The expression level of p53 protein in each dose group of ascorbic acid was lower than that of nickel refined dust group, and the difference was statistically significant (P<0.05). Conclusion: With the increase of concentration of ascorbic acid, oxidative damage levels, antioxidant enzyme levels, reduce cell apoptosis, reduce expression of p53, increased expression of Bcl-2. It showed that ascorbic acid had protective effect on NIH/3T3 cell injury induced by nickel refining dust.

The Preventive Effects of Different Doses of Glucomannan on Experimental Aflatoxicosis in Japanese Quails

ABSTRACT This experimental study was performed to investigate whether there is a protective effect of different doses of Glucomannan using against aflatoxicosis in Japanese quail, and pathological changes and relative organ weights were compared. In the experiment, 60 one-day old male Japanese quails were used as divided into six different groups. Experimental groups were designated as Control(C), aflatoxin(A), glucomannan(GM), 2-fold dose of glucomannan(2GM), aflatoxin+glucomannan(A+GM) and aflatoxin+2-fold dose of glucomannan(A+2GM). While control group quails fed the standard ration as ad libitum, other groups were fed with the administrations additionally to standard diet respectively; 2mg/kg of aflatoxin to group A, 1g/kg of glucomannan to group GM, 2g/kg of glucomannan to group 2GM, 2mg/kg of aflatoxin and 1g/kg glucomannan to group A+GM, 2mg/kg of aflatoxin and 2g/kg glucomannan to group A+2GM. All quails were euthanized at day 21 of the study and organs, (liver, spleen, kidney, thymus and bursa of Fabricius) were removed, weighed and subjected to routine histopathological procedures. Although any important macroscopic changes were not observed in the C, GM and 2GM groups, significant pathological changes were found in the groups of A, A+GM and A+2GM. In the A+GM group, the partial reduction in the severity of microscopic lesions were seen in liver, bursa of Fabricius, thymus and spleen, however a significant reduction in severity of lesions was noticed in A+2GM group. As a result of the study, 2g/kg of glucomannan has been found pathologically to be more effective than 1g/kg glucomannan in terms of the protection against aflatoxicosis by giving orally.

EFFECTS OF ROSUVASTATIN IN EXPERIMENTALLY-INDUCED CARDIAC ISCHEMIA AND ON AORTIC VASCULAR REACTIVITY.

Myocardial infarction (MI) continues to be a major public health problem in the world. The present study aimed to elucidate the protective effect of different doses of rosuvastatin and cilostazol, as well as their combination on isoprenaline-induced MI in rats as well as their effects on isolated aorta. Methods: I- Adult rats received different doses of rosuvastatin (1,2,5,10, & 20mg/kg), cilostazol (18mg/kg) and combination of rosuvastatin 1mg/kg and cilostazol 18mg/kg by oral gavage daily for 16 days, then rats were subcutaneously injected with two doses 24-h apart of 150mg/kg isoprenaline in the last two days. ECG pattern was monitored, myocardial injury markers (CK-MB and LDH) and inflammatory biomarker (CRP) were measured in serum. MDA, catalase and SOD were quantified in cardiac homogenates and heart tissue damage was examined by histopathology. II- Effects of rosuvastatin (0.2 µg/ml – 6.4 µg/ml), cilostazol (7.5 µg/ml – 480 µg/ml) and combination cilostazol (30 µg/ml) and rosuvastatin (0.2 µg/ml – 6.4 µg/ml) on NE-induced contraction in rabbit aortic strip were recorded. Each dose of either rosuvastatin or cilostazol were incubated for 10 min and 15min respectively then NE (0.5 µg/ml) was added and the contraction was recorded for one and half min. Results: I- Pretreatment with different doses of rosuvastatin (1,2,5 & 10), cilostazol 18mg/kg and the combination markedly ameliorated ISO-induced alterations in ECG, cardiac markers, inflammatory marker, oxidative markers and heart architecture. However, protection disappeared at higher dose of rosuvastatin 20mg/kg. II- Addition of either rosuvastatin (0.2-6.4 µg/ml), cilostazol (7.5-480µg/ml) or combination rosuvastatin (0.2-6.4 µg/ml) and cilostazol 30µg/ml produced a significant decrease in the height of NE-induced contraction in a dose dependent manner. Conclusion: I-This study provides evidence that rosuvastatin, cilostazol and their combination possess cardioprotective effect on isoprenaline-induced myocardial infarction. II- The drugs had vasorelaxant effect on aorta. Mechanism of drug action are discussed.

Effect of different doses of pregabalin on skeletal muscle ischaemia-reperfusion injury in rats.

Analgesic, anti-inflammatory and anti-apoptotic effects of pregabalin have been shown previously. In this study, we investigated the protective effect of different doses of pregabalin on skeletal muscle IR injury in rats. 24 rats were randomly divided into 4 groups (Control, Ischaemia-Reperfusion (IR), IR-Pregabalin 50 mg, IR-Pregabalin 200 mg). Following IR, serum Ischemia Modified Albumin (IMA) and tissue Paraoxonase (PON) were studied and gastrocnemius muscle tissue was removed for histopathologic examination. Interstitial inflammation was higher in the IR group than in the control and Pregabalin 200 mg groups (p = 0.037, p = 0.037, respectively). Congestion was higher in the IR group than in the control, Pregabalin 50 and 200 mg groups (p = 0.001, p = 0.004, p = 0.004, respectively). PON was lower in the IR group than in the Control, Pregabalin 50 and 200 mg groups (p = 0.001, p = 0.007, p = 0.015, respectively). IMA was higher in the IR group than in the Control, Pregabalin 50 and 200 mg groups (p < 0.0001, all). We think that administration of pregabalin, more prominent at 200 mg, can reverse the injury that occurs in the skeletal muscle of IR-induced rats. Pregabalin can be safely used for analgesia in cases of IR (Tab. 2, Fig. 9, Ref. 41).

Cistanche tubulosa Protects Dopaminergic Neurons through Regulation of Apoptosis and Glial Cell-Derived Neurotrophic Factor: in vivo and in vitro.

Parkinson’s disease (PD) is a neurodegenerative disease with the pathological hallmark of reduced nigrostriatal dopamine. In traditional Chinese medicine (TCM) clinical practice, the nanopowder of Cistanche tubulosa has therapeutic effects on PD. To identify the therapeutic mechanism, this study tested the protective effect of different doses of MPP+-induced toxicity in MES23.5 cells using the MTT assay and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice (vehicles). Immunohistochemistry was used to assess cytomorphology and tyrosine hydroxylase (TH) expression. Behavioral tests in vehicles, high performance liquid chromatography (HPLC) tests in dopamine, immunohistochemistry and western blot analysis were used to detect the expression of TH, glial cell line-derived neurotrophic factor (GDNF) and its receptors. Our results demonstrated that the C. tubulosa nanopowder improved the viability of MPP+-treated cells, increased TH expression and reduced the number of apoptotic cells. It also increased Bcl2 protein expression and suppressed Bax protein expression in MPP+-treated cells in a dose-dependent manner. In addition, C. tubulosa nanopowder improved the behavioral deficits in vehicle mice, reduced the stationary duration of swimming, enhanced the ability for spontaneous activity and increased the expression of GDNF, the GDNF family receptor alpha (GFRα1) and Ret in cells of the substantia nigra (SN). Furthermore, the protein expression of GDNF, GFRα1 and Ret increased after treatment with different doses of C. tubulosa nanopowder, with a significant difference between the high-dose and vehicle groups. The protein expression of Bcl2 and Bax were similar in the in vivo and in vitro, which suggested that C. tubulosa nanopowder has anti-apoptotic effects in neurons.

The dose-dependent protective effect of curcumin on hepatocyte of rats with sepsis

To observe the protective effect of different doses of curcumin on hepatocytes of rats with sepsis. 100 healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, and low, medium, high dose curcumin intervention groups (L-cur, M-cur, H-cur groups), with 20 rats in each group. The animal model of sepsis was reproduced by cecal ligation and puncture (CLP) method, and in the sham operation group the cecum was just taken out and returned. In the L-cur, M-cur, H-cur groups curcumin was immediately injected after CLP with a dose of 50, 100, 150 mg/kg, respectively, and the rats in sham operation group and sepsis group were given the same amount of normal saline. Five rats in each group were sacrificed at 2, 6, 12, 24 hours after operation, and the hepatic tissues and blood samples were obtained. The pathological changes in hepatic tissues were observed under a microscope, and hepatocytes apoptosis and apoptosis index (AI) of hepatocytes were determined with transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method, and the levels of serum procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined with enzyme linked immunosorbent assay (ELISA) method. Microscopic examination showed that the damage degree of hepatic tissues was significantly increased in sepsis group; the number of apoptotic cells and damage degree of hepatic tissues were increased gradually over time. The damage degree of hepatic tissues in curcumin groups was lessened as compared with sepsis group, especially in M-cur group. There were no significant changes in AI and serum PCT, TNF-α, and IL-1β levels at any of the time points tested in the sham operation group. The AI, serum PCT, TNF-α, and IL-1β levels in the sepsis group were significantly higher than those in the sham operation group from 2 hours after operation on [AI: (23.59±2.00)% vs. (2.02±0.13)%, PCT (μg/L): 2.41±0.21 vs. 0.81±0.01, TNF-α (ng/L): 217.28±14.24 vs. 80.02±2.26, IL-1β (ng/L): 61.84±3.21 vs. 25.78±1.29, all P < 0.05], and they showed a gradually increasing tendency. AI reached peak value at 24 hours after operation [(52.05±1.31)%]; PCT, TNF-α and IL-1β reached the peak values at 12 hours after operation [(8.68±0.58) μg/L, (314.13±14.39) ng/L, (132.24±2.58) ng/L, respectively]. Curcumin intervention significantly reduced the levels of AI, TNF-α, PCT and IL-1β in hepatocytes of septic rats, especially in M-cur group [AI: (11.56±0.96)% vs. (23.59±2.00)% at 2 hours, (30.35±1.20)% vs. (52.05±1.31)% at 24 hours; PCT (μg/L): 1.13±0.19 vs. 2.41±0.21 at 2 hours, 5.09±0.42 vs. 8.68±0.58 at 12 hours; TNF-α (ng/L): 124.73±7.47 vs. 217.28±14.24 at 2 hours, 168.68±6.95 vs. 314.13±14.39 at 12 hours; IL-1β (ng/L): 35.05±1.00 vs. 61.84±3.21 at 2 hours, 84.06±3.42 vs. 132.24±2.58 at 12 hours; all P < 0.05]. Curcumin can inhibit the inflammatory reaction of hepatocytes of rats, prevent apoptosis, and protect the hepatocytes of rats with sepsis. The concentration of curcumin with the most significant effect is 100 mg/kg, which is the medium dosage.

Evaluation the protective effect of diphenhydramin against acute toxicity induced by levamisole in male mice

The aim of this study was to evaluate the protective effect of different doses of diphenhydramin against acute toxicosiswith Levamisole. The Mechanism of levamisole induced acute toxicity and that of protective effect of diphenhydramin againstLevamisole toxicosis also examined on the level of cholinesterase (ChE) activity. Subcutanous injection of 100mg/kglevamisole in male mice with induced cholinergic over stimulation and death in 100% of animals. The Toxicosis was notrelated to the significantly decreased in plasma, red blood cells and brain ChE activity. Injection low dose of diphenhydramin2.5mg/kg S.C. 15 min before levamisole produced protective effect against acute toxicity with levamisole. Significantlydecreased the severity of toxicosis and increased survival rates to 100%. Diphenhydramin at low dose alone or with acute doseof levamisole did not Produced Significantly inhibition in ChE activity.The data suggested that the toxic effect of Levamisolewas not related to inhibition of ChE. The low dose of diphenhydramin protected mice from Levamisole toxicity. The antidoataleffect of diphenhydramin not at the level of protection from ChE inhibition. There was no adverse interaction between twodrugs.

Study of Protective Action of Spondias pinnata Bark extract on Rat Liver and Kidney against Etoposide Induced Chemical Stress

Introduction: System injury, manifested as metabolic dysfunction is a common side effect of chemotherapy. Chemical stress on hepatic and kidney cells can be evaluated by biochemical analysis, including serum aminotransferases, glutathione levels and extent of lipid peroxidation. Combined treatment of chemotherapy along with the natural products such as phytochemicals may be a newer approach to reduce the side effects and betterment of chemotherapy. Objective: The present study was conducted to assay kidney and liver associated parameters on animals exposed to etoposide, and the protective effect of different doses of Spondias pinnata bark extract on normal cells. In this study, total 24 male Wistar rats ( either sex) aged between 60 to 90 days were considered. Each group consisted of six rats. Levels of Alanine and Aspartate aminotransferases were estimated using semi-auto analyser and GSH, GST, TAO and LPx by spectrophotometry. Results and Conclusion: Data analyzed using Graph Pad 5.0. Variation in the analyzed parameters were found between control, chemotherapy and Spondias pinnata groups. Results of the study show that significant increase in TBARS levels indicative of etoposide induced oxidative stress could be prevented by treatment with S. pinnata. GST levels also support the preventive action of S. pinnata against etoposide induced stress. However, TAO and transaminases remain unaltered in the study groups

Effect of Ascorbic Acid on Noise Induced Hearing Loss in Rats.

After presbycusis, noise-induced hearing loss is the second most common cause of acquired hearing loss. Numerous studies have shown that high-intensity noise exposure increasesfree radical species;therefore, use ofantioxidants to detoxify the free radicals can prevent cellular damage in the cochlea. We studied the potential hearing protective effect of different doses of ascorbic acid administered prior to noise exposure in rats. Twenty-four male albino Wistar rats were randomly allocated into four groups: groups A, B, and C received 1250, 250, and 50 mg/kg/day of ascorbic acid, respectively, and group D acted as the control group. After 14 days of ascorbic acid administration, the rats were exposed to noise (105 dB sound pressure level for 2 h). Distortion product otoacoustic emissions (DPOAE) were recorded prior to starting the ascorbic acid as baseline and 1 h after the noise exposure. The amplitude decrease was 14.99 dB for group A, 16.11 dB for group B, 28.82 dB for group C, and 29.91 dB for the control group. Moderate and high doses of ascorbic acid significantly reduced the transient threshold shift in the rats. The results of present study support the concept of cochlea protection by antioxidant agents. This dose-dependent protective effect was shown through the use of ascorbic acid treatment prior to noise exposure.

The protective effect of different doses of dexamethasone on acute kidney injury induced by sepsis in mice

To investigate the effect of different doses of dexamethasone (DEX) on sepsis induced acute kidney injury (AKI). One hundred and thirty healthy male Kunming mice were randomly divided into sham group, sepsis group, physiological-dose DEX group (0.12 mg/kg), stress-dose DEX group (1.2 mg/kg), and high-dose DEX group (12 mg/kg). The sepsis model was reproduced by cecal ligation and puncture (CLP) method. Histopathological changes in the kidney were observed at 24 hours and 48 hours after CLP. The expressions of glucocorticoid receptor-α (GR-α) in the kidney were detected by immunohistochemistry. The levels of GR-α mRNA and nuclear factor-ΚB (NF-ΚB) mRNA were determined by real-time polymerase chain reaction (PCR). The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the plasma were measured by enzyme linked immunosorbent assay (ELISA). Compared with sham group mice, sepsis mice showed serious impairment in renal tubules. The mRNA and protein expression of GR-α were decreased, and NF-ΚB mRNA, plasma TNF-α and IL-1β were elevated. Compared with sepsis group, the histopathological changes in the kidney were mitigated with different levels in groups treated with different doses of DEX. GR-α protein and mRNA were up-regulated, NF-ΚB mRNA and plasma TNF-α, IL-1β were down-regulated obviously. The best effect could be seen in physiological DEX group [AKI score: 24 hours 1.480±0.334 vs. 3.040±0.517, 48 hours 1.840±0.167 vs. 3.400±0.400; GR-α protein (A value): 24 hours 0.102±0.009 vs. 0.088±0.005, 48 hours 0.103±0.008 vs. 0.085±0.006; GR-α mRNA: 24 hours 0.0400(0.0300, 0.0400) vs. 0.0100(0.0093, 0.0100), 48 hours 0.0350(0.0300, 0.0475) vs. 0.0100(0.0010, 0.0138); NF-ΚB mRNA: 24 hours 0.009±0.001 vs. 0.012±0.000,48 hours 0.011±0.000 vs. 0.013±0.001; TNF-α: 24 hours 105.84±3.84 ng/L vs. 135.52±4.49 ng/L, 48 hours 111.35±3.67 ng/L vs. 141.22±4.46 ng/L; IL-1β: 24 hours 45.71±2.93 ng/L vs. 64. 12±3.62 ng/L, 48 hours 57.04±3.04 ng/L vs. 74.87±3.67 ng/L; P<0.05 or P<0.01]. DEX given in physiological-dose could increase renal GR-α level and alleviate the sepsis induced kidney injury. The protective effect was much better than that of high dose DEX.

Protective effects of caffeic acid phenethyl ester on dose-dependent intoxication of rats with paraquat

Paraquat (PQ; 1,1'dimethyl-bipyridilium 4,4'-dichloride), which is used extensively throughout the world, is highly toxic to humans. We aimed to investigate the protective effects of different doses of caffeic acid phenethyl ester (CAPE) on PQ-intoxicated rats. A total of 80 rats were divided into the following eight groups, comprising 10 rats in each group: group 1: control; group 2: administered with CAPE (10 µmol/kg); group 3: administered with 15 mg/kg PQ (PQ15 group); group 4: administered with 30 mg/kg PQ (PQ30 group); group 5: administered with 45 mg/kg PQ (PQ45 group); group 6: administered with 15 mg/kg PQ + CAPE; group 7: administered with 30 mg/kg PQ + CAPE and group 8: administered with 45 mg/kg PQ + CAPE. Both PQ and CAPE were injected intraperitoneally. Pancreatic tissue was examined with both haematoxylin and eosin and immunochemical staining. The ratio of the immunohistochemical staining area to the total pancreatic area of the β cells revealed that statistically significant differences were observed only between the PQ and PQ + CAPE groups (p < 0.05). The evaluation of the data suggests that CAPE can be used to prevent acute effects of PQ intoxication.

β‐Cryptoxanthin supplementation inhibits carcinogen‐initiated and nicotine‐promoted lung tumor development in AJ mice

Recent epidemiologic studies show that increased dietary β‐cryptoxanthin (BCX) intake, rather than β‐carotene used in earlier human trials, is associated with reduced risk of lung cancer. However, BCX efficacy on lung carcinogenesis has not been reported. Here, we report the protective effects of different doses of BCX against lung carcinogenesis at the initiation and promotion stages in AJ mouse models. In the tobacco carcinogen NNK‐initiated lung carcinogenesis model, we found a 52–63% reduction of lung tumor multiplicity in mice pre‐treated with BCX at 0.2 and 2 mg kg BW‐1 d‐1, as compared to the NNK group, P&lt;0.01. In the NNK‐initiated and nicotine‐promoted lung cancer model, we found that nicotine not only induced emphysema, a risk for lung cancer, but also increased greatly lung tumor multiplicity of the NNK‐treated mice. Notably, BCX at 2 and 4 mg kg BW‐1 d‐1 prevented nicotine‐induced emphysema and decreased tumor multiplicity by 86–91%, P&lt;0.01. BCX protection was associated with suppressions of lung AKT activation, IL‐6 and early growth response‐1 mRNA. Unlike β‐carotene reported in prior animal studies, BCX induced retinoic acid receptor‐β mRNA. By HPLC analysis, liver BCX, not retinol, increased in the BCX supplemented mice. Our data suggest that BCX is a unique chemopreventive agent for lung cancer prevention, which is likely to be independent of its provitamin A activity.Grant Funding Source : NIH R01CA104932

Effect of exogenousphosphocreatine on cardiomycytic apoptosis and expression of Bcl-2 and Bax aftercardiopulmonary resuscitation in rats

：Objective To observe thechanges of cell apoptosis and levels of Bcl-2 and Bax protein in myocardium aftercardiopulmonary resuscitation (CPR) in rats and to study the protective effects ofdifferent doses of exogenous phosphocreatine (creatine phosphate, CP) on cell apoptosis.Methods A total of 32 male adult SD rats were randomly divided into 4 groups, namelycontrol group ( group A), CPR group (group B), low dose CP group (group C, phosphocreatine0. 5 g/kg given at beginning of CPR and 1.0 g/ kg 2 hour after CPR) and high dose CP group( group D, phosphocreatine 1.0 g/kg at beginning of CPR and 2. 0 g/kg 2 hours after CPR) .Cardiac arrest was induced by asphyxiation and CPR was started 7 min after asphyxiation itgroups B, C and D. Myocardium samples were taken 24 hours after CPR for detectingmyocardium cell apoptosis by TUNEL method. The levels of Bcl-2 and Bax protein weremeasured by using immunohistochemistry. Experimental data were processed with varianceanalysis in SPSS package. Results Compared with group A, myocardium cell apoptosis index(AI), and the levels of Bcl-2 and Bax proteinincreased significantly in groups B, C and D(P ＜0. 01 ), and Bcl-2/Bax ratio decreased significantly (P ＜0.01 ) . Compared with group B, myocardium cell AI and levels of Bcl-2 and Bax proteindecreased significantly in groups C and D ( P ＜0. 01 ), andBcl-2/Bax ratio increased significantly ( P ＜0. 01 ).Compared with group C, myocardium cell AI and levels of Bcl-2 and Bax decreasedsignificantly in group D (P ＜ 0. 05 ), and Bcl-2/Bax ratioincreased significantly ( P ＜ 0. 05 ) . Conclusion Exogenous phosphocreatine, especiallyinlarge dose, could inhibit apoptosis of myocardium cells and alleviate myocardium injuryafter CPR in rats. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Myocardialinjury; Phosphocreatine; Apoptosis; Bcl-2; Bax; TUNEL

Effect of Different Doses of Wheatgrass in Prevention of Carbon Tetrachloride Induced Hepatotoxicity in Rats

© 2011, INASL 39 HEPATOTOXICITY Effect of Different Doses of Wheatgrass in Prevention of Carbon Tetrachloride Induced Hepatotoxicity in Rats JK Kamboj*, SV Rana*, DK Dhawan**, K Vahiphei*** Departments of *Gastroenterology and **Pathology, PGIMER, Chandigarh, ***Department of Biophysics, Punjab University, Chandigarh Introduction: Wheatgrass (Triticum aestivum), rich in chlorophyll and various antioxidants, is promoted to treat a number of conditions including common cold, cough, fever, eczema and burns, etc. Aim: To determine the protective effect of different doses of wheatgrass in hepatic tissue of Wistar rats damaged by CCl4. Material and Methods: Wheatgrass was administered orally at different doses of 20 mg, 40 mg, 60 mg and 80 mg/100 g by body weight in drinking water for 4 weeks along with CCl4 injection given subcutaneously at a dose of 2 mL/Kg body weight twice a week. Wheatgrass dose was started 2 weeks prior to first injection of CCl4. Carbon tetrachloride was also administered in control group for 4 weeks and one group was given only wheatgrass at a maximum dose of 80 mg/100 g by body weight/day to check any adverse effect of wheatgrass on liver. The effect to different treatments was studied on serum enzymes like alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats at different time intervals of 2 and 4 weeks and the rat liver was analyzed histologically at the end of study. Results: Serum ALP, AST, ALT activity was significantly increased when estimated at the intervals of 2 and 4 weeks as compared to baseline values in CCl4 group. Interestingly, supplementation of wheatgrass to rats helped in regulating the altered activities of ALP, AST and ALT in serum at 4 weeks. However, wheatgrass treatment to rats did not indicate any significant change in the activities of all abovementioned liver enzymes at the interval of 2 weeks. Histologically, there was necrosis, portal triaditis and lobular inflammation in CCl4 group. Maximum protection was observed biochemically and histologically with wheatgrass dose of 80 mg/100 g body weight Conclusion: Carbon tetrachloride caused liver toxicity and wheatgrass treatment prevented the increase in liver enzymes and histology depending on the dose of wheatgrass. Conflict of Interest: None Relation of NAT2, CYP2E1 and GST Gene Polymorphisms with Anti-tuberculosis Treatment Induced Hepatotoxicity in North Indian Patients SV Rana*, SK Sharma**, RP Ola*, SK Arora***, SK Sinha*, JK Kamboj*, K Singh* Department of Superspecialty of *Gastroenterology, **Biophysics and ***Immunopathology, PGIMER, Chandigarh Background: Antituberculosis treatment (ATT) induced hepatitis is attributed to isoniazid (INH). Isoniazid is metabolized by hepatic N-acetyltransferase-2 (NAT-2) and cytochrome P-450 2E1 (CYP2E1) to form hepatotoxins. Glutathione-S-transferase (GST) plays an important role in prevention of ATT-induced hepatotoxicity. Deficiency of GST activity because of homozygous null mutations at GSTM1 and GSTT1 loci may modulate susceptibility to ATT-induced hepatotoxicity. Aim: To evaluate whether polymorphisms of NAT-2, GST and CYP2E1 gene were associated with ATT-induced hepatotoxicity in North Indian patients. Methods: In this prospective study, 250 patients treated with ATT for tuberculosis were genotyped for polymorphisms of NAT-2, GST and CYP2E1. NAT-2, CYP2E1 and GST genotypes were determined by PCR and multiplex PCR with restriction fragment length polymorphism analysis (RFLP). Results: Two hundred fifty tuberculosis (TB) patients on ATT (153 males) were studied. Out of 250 patients, 32 (12.8%) developed hepatotoxicity. NAT-2 gene allele 4/4 was present in 18/32 (56.2%) of hepatotoxicity patients while in 76/218 (34.8%) in non-hepatotoxicity patients. Allele 4/6, 5/5, 6/6 and 7/7 were not present in hepatotoxicity patients while these were present in non-hepatotoxicity patients. In GST, out of 32 hepatotoxicity patients, 5 (15.6%) showed GSTM1, 9 out of 32 (28.0%) GSTT1 and 18 out of 32 (56.3%) GSTT1/ GSTM1/s-globulin. While 69 out of 218 (31.7%) showed GSTM1, 34 (15.6%) GSTT1, and 115 (52.7%) GSTT1/GSTM1/s-globulin in nonhepatotoxicity patients. For CYP2E1 c1/c1, c2/c2 and c1/c2 genotypes in INH-NH patients were 61.1%, 16.6% and 22.2% respectively while in INH-H patients 50.0%, 25.0% and 25.0% respectively. Conclusion: This study suggests that NAT-2 gene allele 4/4 was significantly higher in INH-induced hepatotoxicity as compared to nonhepatotoxicity group. There was no significant difference in CYP2E1 and GST genotypes between both the groups. Conflict of Interest: None 03_JCEH-Abstract.indd 39 3/18/2011 11:13:05 AM