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  1. Fulltext Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet)
    Taha MM, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S
    Chem Biol Interact, 2010 Aug 05;186(3):295-305.
    PMID: 20452335 DOI: 10.1016/j.cbi.2010.04.029
    Zerumbone (ZER), a monosesquiterpene found in the subtropical ginger (Zingiber zerumbet Smith), possesses antiproliferative properties to several cancer cells lines, including the cervical, skin and colon cancers. In this study, the antitumourigenic effects of ZER were assessed in rats induced to develop liver cancer with a single intraperitoneal injection of diethylnitrosamine (DEN, 200 mg/kg) and dietary 2-acetylaminofluorene (AAF) (0.02%). The rats also received intraperitoneal ZER injections at 15, 30 or 60 mg/kg body wt. twice a week for 11 weeks, beginning week four post-DEN injection. The hepatocytes of positive control (DEN/AAF) rats were smaller with larger hyperchromatic nuclei than normal, showing cytoplasmic granulation and intracytoplasmic violaceous material, which were characteristics of hepatocarcinogenesis. Histopathological evaluations showed that ZER protects the rat liver from the carcinogenic effects of DEN and AAF. Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AP) and alpha-fetoprotein (AFP) were significantly lower (P<0.05) in ZER-treated than untreated rats with liver cancer. The liver malondialdehyde (MDA) concentrations significantly (P<0.05) increased in the untreated DEN/AAF rats indicating hepatic lipid peroxidation. There was also significant (P<0.05) reduction in the hepatic tissue glutathione (GSH) concentrations. The liver sections of untreated DEN/AAF rats also showed abundant proliferating cell nuclear antigen (PCNA), while in ZER-treated rats the expression of this antigen was significantly (P<0.05) lowered. By the TUNEL assay, there were significantly (P<0.05) higher numbers of apoptotic cells in DEN/AAF rats treated with ZER than those untreated. Zerumbone treatment had also increased Bax and decreased Bcl-2 protein expression in the livers of DEN/AAF rats, which suggested increased apoptosis. Even after 11 weeks of ZER treatment, there was no evidence of abnormality in the liver of normal rats. This study suggests that ZER reduces oxidative stress, inhibits proliferation, induces mitochondria-regulated apoptosis, thus minimising DEN/AAF-induced carcinogenesis in rat liver. Therefore, ZER has great potential in the treatment of liver cancers.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  2. Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats
    Gupta M, Gulati M, Kapoor B, Kumar B, Kumar R, Kumar R, et al.
    J Ethnopharmacol, 2021 Jul 15;275:114115.
    PMID: 33852947 DOI: 10.1016/j.jep.2021.114115
    ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant.

    AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta.

    MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied.

    RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner.

    CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

    Matched MeSH terms: Rats, Wistar; Rats
  3. Pharmacological evaluation of vanillic acid in rotenone-induced Parkinson's disease rat model
    Sharma N, Khurana N, Muthuraman A, Utreja P
    Eur J Pharmacol, 2021 Jul 15;903:174112.
    PMID: 33901458 DOI: 10.1016/j.ejphar.2021.174112
    In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P 
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  4. The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats
    Armenia A, Munavvar AS, Abdullah NA, Helmi A, Johns EJ
    Br J Pharmacol, 2004 Jun;142(4):719-26.
    PMID: 15172958
    1. Diabetes and hypertension are both associated with an increased risk of renal disease and are associated with neuropathies, which can cause defective autonomic control of major organs including the kidney. This study aimed to examine the alpha(1)-adrenoceptor subtype(s) involved in mediating adrenergically induced renal vasoconstriction in a rat model of diabetes and hypertension. 2. Male spontaneously hypertensive rats (SHR), 220-280 g, were anaesthetized with sodium pentobarbitone 7-day poststreptozotocin (55 mg x kg(-1) i.p.) treatment. The reductions in renal blood flow (RBF) induced by increasing frequencies of electrical renal nerve stimulation (RNS), close intrarenal bolus doses of noradrenaline (NA), phenylephrine (PE) or methoxamine were determined before and after administration of nitrendipine (Nit), 5-methylurapidil (5-MeU), chloroethylclonidine (CEC) and BMY 7378. 3. In the nondiabetic SHR group, mean arterial pressure (MAP) was 146+/-6 mmHg, RBF was 28.0+/-1.4 ml x min(-1) x kg(-1) and blood glucose was 112.3+/-4.7 mg x dl(-1), and in the diabetic SHR Group, MAP was 144+/-3 mmHg, RBF 26.9+/-1.3 ml(-1) min x kg(-1) and blood glucose 316.2+/-10.5 mg x dl(-1). Nit, 5-MeU and BMY 7378 blunted all the adrenergically induced renal vasoconstrictor responses in SHR and diabetic SHR by 25-35% (all P<0.05), but in diabetic rats the responses induced by RNS and NA treated with 5-MeU were not changed. By contrast, during the administration of CEC, vasoconstrictor responses to all agonists were enhanced by 20-25% (all P<0.05) in both the SHR and diabetic SHR. 4. These findings suggest that alpha(1A) and alpha(1D)-adrenoceptor subtypes contribute in mediating the adrenergically induced constriction of the renal vasculature in both the SHR and diabetic SHR. There was also an indication of a greater contribution of presynaptic adrenoceptors, that is, alpha(1B)-, and/or alpha(2)-subtypes.
    Matched MeSH terms: Rats, Inbred SHR; Rats
  5. Fulltext Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation
    Batumalaie K, Amin MA, Murugan DD, Sattar MZ, Abdullah NA
    Sci Rep, 2016 06 02;6:27236.
    PMID: 27250532 DOI: 10.1038/srep27236
    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings.
    Matched MeSH terms: Rats
  6. Ellagic acid in Emblica officinalis exerts anti-diabetic activity through the action on β-cells of pancreas
    Fatima N, Hafizur RM, Hameed A, Ahmed S, Nisar M, Kabir N
    Eur J Nutr, 2017 Mar;56(2):591-601.
    PMID: 26593435 DOI: 10.1007/s00394-015-1103-y
    PURPOSE: The present study was undertaken to explore the possible anti-diabetic mechanism(s) of Emblica officinalis (EO) and its active constituent, ellagic acid (EA), in vitro and in vivo.

    METHOD: Neonatal streptozotocin-induced non-obese type 2 diabetic rats were treated with a methanolic extract of EO (250 or 500 mg/kg) for 28 days, and blood glucose, serum insulin, and plasma antioxidant status were measured. Insulin and glucagon immunostaining and morphometry were performed in pancreatic section, and liver TBARS and GSH levels were measured. Additionally, EA was tested for glucose-stimulated insulin secretion and glucose tolerance test.

    RESULTS: Treatment with EO extract resulted in a significant decrease in the fasting blood glucose in a dose- and time-dependent manner in the diabetic rats. It significantly increased serum insulin in the diabetic rats in a dose-dependent manner. Insulin-to-glucose ratio was also increased by EO treatment. Immunostaining of pancreas showed that EO250 increased β-cell size, but EO500 increased β-cells number in diabetic rats. EO significantly increased plasma total antioxidants and liver GSH and decreased liver TBARS. EA stimulated glucose-stimulated insulin secretion from isolated islets and decreased glucose intolerance in diabetic rats.

    CONCLUSION: Ellagic acid in EO exerts anti-diabetic activity through the action on β-cells of pancreas that stimulates insulin secretion and decreases glucose intolerance.

    Matched MeSH terms: Rats
  7. Antioxidant and anti-inflammatory activities contribute to the prophylactic effect of semi-purified fractions obtained from the crude methanol extract of Muntingia calabura leaves against gastric ulceration in rats
    Balan T, Sani MH, Mumtaz Ahmad SH, Suppaiah V, Mohtarrudin N, Zakaria ZA
    J Ethnopharmacol, 2015 Apr 22;164:1-15.
    PMID: 25540923 DOI: 10.1016/j.jep.2014.12.017
    In traditional medicine, the leaves, flowers, barks and roots of Muntingia calabura L. (Muntingiaceae) have been employed as a treatment for various ailments including dyspepsia and to relieve pain caused by gastritis and peptic ulcer disease. The methanolic extract of Muntingia calabura leaves (MEMC) has been proven in the previous study to possess significant antiulcer activity. In this study, we attempted to determine the prophylactic effect of the fractions obtained from MEMC against ethanol-induced gastric lesion in rats and the involvement of antioxidants and anti-inflammatory mediators.
    Matched MeSH terms: Rats, Sprague-Dawley
  8. Fulltext Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats
    Atangwho IJ, Yin KB, Umar MI, Ahmad M, Asmawi MZ
    BMC Complement Altern Med, 2014;14:426.
    PMID: 25358757 DOI: 10.1186/1472-6882-14-426
    This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.
    Matched MeSH terms: Rats
  9. Para-phenylenediamine-induces apoptosis via a pathway dependent on PTK-Ras-Raf-JNK activation but independent of the PI3K/Akt pathway in NRK-52E cells
    Kasi RA, Moi CS, Kien YW, Yian KR, Chin NW, Yen NK, et al.
    Mol Med Rep, 2015 Mar;11(3):2262-8.
    PMID: 25411820 DOI: 10.3892/mmr.2014.2979
    para‑Phenylenediamine (p‑PD) is a potential carcinogen, and widely used in marketed hair dye formulations. In the present study, the role of the protein tyrosine kinase (PTK)/Ras/Raf/c‑Jun N‑terminal kinase (JNK) and phosphoinositide 3‑kinase (PI3k)/protein kinase B (Akt) pathways on the growth of NRK‑52E cells was investigated. The results demonstrated that p‑PD reduced cell viability in a dose‑dependent manner. The cell death due to apoptosis was confirmed by cell cycle analysis and an Annexin‑V‑fluorescein isothiocyanate binding assay. Subsequent to staining with 2',7'‑dichlorofluorescin diacetate, the treated cells demonstrated a significant increase in reactive oxygen species (ROS) generation compared with the controls. The effects of p‑PD on the signalling pathways were analysed by western blotting. p‑PD‑treated cells exhibited an upregulated phospho‑stress‑activated protein kinase/JNK protein expression level and downregulated Ras and Raf protein expression levels; however, Akt, Bcl‑2, Bcl‑XL and Bad protein expression levels were not significantly altered compared with the control. In conclusion, p‑PD induced apoptosis by a PTK/Ras/Raf/JNK‑dependent pathway and was independent of the PI3K/Akt pathway in NRK‑52E cells.
    Matched MeSH terms: Rats
  10. Quercetin induces morphological and proliferative changes of rat's uteri under estrogen and progesterone influences
    Shahzad H, Giribabu N, Muniandy S, Salleh N
    Int J Clin Exp Pathol, 2014;7(9):5484-94.
    PMID: 25337190
    This study investigated the effect of 10 or 100 mg/kg/day quercetin on the uterus of ovariectomized adult female rats receiving sex-steroid replacement regime mimicking changes in hormonal profiles during the reproductive cycle. Following seven days of treatment with estrogen and progesterone with or without quercetin, uteri were harvested for histological and proliferative cell nuclear antigen (PCNA) protein and mRNA expression and PCNA protein distribution analyses. Our findings indicated that co-administration of 10 mg/kg/day quercetin with estrogen and progesterone caused a significant decrease in the size of uterine lumen and epithelial heights with lower PCNA protein and mRNA expression as compared to estrogen plus progesterone-only treatment (P < 0.05). Concomitant treatment with estrogen and progesterone with 100 mg/kg/day quercetin resulted in a marked increase in the number of glands with increased PCNA protein and mRNA expression. Significantly higher PCNA distribution was observed in the stroma and glands as compared to estrogen plus progesterone-only treatment (P < 0.05). In conclusion, at 10 mg/kg/day, quercetin affects uterine morphology but not proliferation, however at 100 mg/kg/day, quercetin induced significant stromal and glandular proliferation which could predispose the uterus towards neoplastic development.
    Matched MeSH terms: Rats, Sprague-Dawley
  11. Possible role of GABA-B receptor modulation in MPTP induced Parkinson's disease in rats
    Tyagi RK, Bisht R, Pant J, Kumar P, Majeed AB, Prakash A
    Exp. Toxicol. Pathol., 2015 Feb;67(2):211-7.
    PMID: 25547370 DOI: 10.1016/j.etp.2014.12.001
    Accumulating evidence strongly suggests that gamma amino butyric acid (GABA) receptors play a crucial role in the pathogenesis of Parkinson's disease (PD). Therefore, the present study was designed to investigate the role of GABA-B receptor modulation in experimental models of MPTP-induced PD. MPTP was administered repeatedly on 1st, 7th and 14th day intranigrally for the induction of PD in Male Wistar rats. Baclofen (10 and 20mg/kg) and GABA-B antagonist CGP35348 (10mg/kg) were given after induction of PD for 14 days. Different behavioural tasks were performed during 1st, 14th, 21st, 28th days after MPTP injection and biochemical parameters were estimated on day 28th. Central administration of MPTP showed significant impairment of motor behaviour and marked increase of oxidative damage LPO and GSH in striatum and cortex. Pro-inflammatory cytokines like TNF-α and IL-β were significantly increased in striatum region of MPTP treated rats. However, post treatment with baclofen significantly improved the motor abnormalities and attenuated the oxidative damage and neuro-inflammation in MPTP treated rats. CGP35348, GABA-B receptor antagonist, reversed the protective effect of baclofen GABA-B receptor play role in the neuroprotection. The present study concluded that baclofen produce beneficial effect against MPTP induced PD like symptoms rats through GABAergic mechanism.
    Matched MeSH terms: Rats, Wistar
  12. Anterior and posterior segment changes in rat eyes with chronic steroid administration and their responsiveness to antiglaucoma drugs
    Razali N, Agarwal R, Agarwal P, Kapitonova MY, Kannan Kutty M, Smirnov A, et al.
    Eur J Pharmacol, 2015 Feb 15;749:73-80.
    PMID: 25481859 DOI: 10.1016/j.ejphar.2014.11.029
    Steroid-induced ocular hypertension (SIOH) is associated with topical and systemic use of steroids. However, SIOH-associated anterior and posterior segment morphological changes in rats have not been described widely. Here we describe the pattern of intraocular pressure (IOP) changes, quantitative assessment of trabecular meshwork (TM) and retinal morphological changes and changes in retinal redox status in response to chronic dexamethasone treatment in rats. We also evaluated the responsiveness of steroid-pretreated rat eyes to 5 different classes of antiglaucoma drugs that act by different mechanisms. Up to 80% of dexamethasone treated animals achieved significant and sustained IOP elevation. TM thickness was significantly increased and number of TM cells was significantly reduced in SIOH rats compared to the vehicle-treated rats. Quantitative assessment of retinal morphology showed significantly reduced thickness of ganglion cell layer (GCL) and inner retina (IR) in SIOH rats compared to vehicle-treated rats. Estimation of retinal antioxidants including catalase, superoxide dismutase and glutathione showed significantly increased retinal oxidative stress in SIOH animals. Furthermore, steroid-treated eyes showed significant IOP lowering in response to treatment with 5 different drug classes. This indicated the ability of SIOH eyes to respond to drugs acting by different mechanisms. In conclusion, SIOH was associated with significant morphological changes in TM and retina and retinal redox status. Additionally, SIOH eyes also showed IOP lowering in response to drugs that act by different mechanisms of action. Hence, SIOH rats appear to be an inexpensive and noninvasive model for studying the experimental antiglaucoma drugs for IOP lowering and neuroprotective effects.
    Matched MeSH terms: Rats, Sprague-Dawley
  13. Fulltext Impact of ellagic acid in bone formation after tooth extraction: an experimental study on diabetic rats
    Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Hussaini J, Khor GH
    ScientificWorldJournal, 2014;2014:908098.
    PMID: 25485304 DOI: 10.1155/2014/908098
    To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction.
    Matched MeSH terms: Rats, Sprague-Dawley
  14. Antioxidative and chemopreventive effects of Nephrolepis biserrata against carbon tetrachloride (CCl4)-induced oxidative stress and hepatic dysfunction in rats
    Shah MD, Gnanaraj C, Haque AT, Iqbal M
    Pharm Biol, 2015 Jan;53(1):31-9.
    PMID: 25243876 DOI: 10.3109/13880209.2014.909502
    Nephrolepis biserrata L. (Nephrolepidaceae) has been used in folk medicine for protection against different diseases.
    Matched MeSH terms: Rats, Sprague-Dawley
  15. Fulltext Ferulago angulata activates intrinsic pathway of apoptosis in MCF-7 cells associated with G1 cell cycle arrest via involvement of p21/p27
    Karimian H, Moghadamtousi SZ, Fadaeinasab M, Golbabapour S, Razavi M, Hajrezaie M, et al.
    Drug Des Devel Ther, 2014;8:1481-97.
    PMID: 25278746 DOI: 10.2147/DDDT.S68818
    Ferulago angulata is a medicinal plant that is traditionally known for its anti-inflammatory and antiulcer properties. The present study was aimed to evaluate its anticancer activity and the possible mechanism of action using MCF-7 as an in vitro model. F. angulata leaf extracts were prepared using solvents in the order of increasing polarity. As determined by MTT assay, F. angulata leaves hexane extract (FALHE) revealed the strongest cytotoxicity against MCF-7 cells with the half maximal inhibitory concentration (IC50) value of 5.3 ± 0.82 μg/mL. The acute toxicity study of FALHE provided evidence of the safety of the plant extract. Microscopic and flow cytometric analysis using annexin-V probe showed an induction of apoptosis in MCF-7 by FALHE. Treatment of MCF-7 cells with FALHE encouraged the intrinsic pathway of apoptosis, with cell death transducing signals that reduced the mitochondrial membrane potential with cytochrome c release from mitochondria to cytosol. The released cytochrome c triggered the activation of caspase-9. Meanwhile, the overexpression of caspase-8 suggested the involvement of an extrinsic pathway in the induced apoptosis at the late stage of treatment. Moreover, flow cytometric analysis showed that FALHE treatment significantly arrested MCF-7 cells in the G1 phase, which was associated with upregulation of p21 and p27 assessed by quantitative polymerase chain reaction. Immunofluorescence and the quantitative polymerase chain reaction analysis of MCF-7 cells after treatment with FALHE revealed an upregulation of Bax and a downregulation of Bcl-2 proteins. These findings proposed that FALHE suppressed the proliferation of MCF-7 cells via cell cycle arrest and the induction of apoptosis through intrinsic pathway.
    Matched MeSH terms: Rats
  16. Fulltext Biocompatibility and toxicity of poly(vinyl alcohol)/N,O-carboxymethyl chitosan scaffold
    Kamarul T, Krishnamurithy G, Salih ND, Ibrahim NS, Raghavendran HR, Suhaeb AR, et al.
    ScientificWorldJournal, 2014;2014:905103.
    PMID: 25298970 DOI: 10.1155/2014/905103
    The in vivo biocompatibility and toxicity of PVA/NOCC scaffold were tested by comparing them with those of a biocompatible inert material HAM in a rat model. On Day 5, changes in the blood parameters of the PVA/NOCC-implanted rats were significantly higher than those of the control. The levels of potassium, creatinine, total protein, A/G, hemoglobulin, erythrocytes, WBC, and platelets were not significantly altered in the HAM-implanted rats, when compared with those in the control. On Day 10, an increase in potassium, urea, and GGT levels and a decrease in ALP, platelet, and eosinophil levels were noted in the PVA/NOCC-implanted rats, when compared with control. These changes were almost similar to those noted in the HAM-implanted rats, except for the unaltered potassium and increased neutrophil levels. On Day 15, the total protein, A/G, lymphocyte, monocyte, and eosinophil levels remained unaltered in the PVA/NOCC-implanted rats, whereas urea, A/G, WBC, lymphocyte, and monocyte levels remained unchanged in the HAM-implanted rats. Histology and immunohistochemistry analyses revealed inflammatory infiltration in the PVA/NOCC-implanted rats, but not in the HAM-implanted rats. Although a low toxic tissue response was observed in the PVA/NOCC-implanted rats, further studies are necessary to justify the use of this material in tissue engineering applications.
    Matched MeSH terms: Rats, Sprague-Dawley
  17. Abuse potential and adverse cognitive effects of mitragynine (kratom)
    Yusoff NH, Suhaimi FW, Vadivelu RK, Hassan Z, Rümler A, Rotter A, et al.
    Addict Biol, 2016 Jan;21(1):98-110.
    PMID: 25262913 DOI: 10.1111/adb.12185
    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug.
    Matched MeSH terms: Rats
  18. Fenofibrate and dipyridamole treatments in low-doses either alone or in combination blunted the development of nephropathy in diabetic rats
    Balakumar P, Varatharajan R, Nyo YH, Renushia R, Raaginey D, Oh AN, et al.
    Pharmacol Res, 2014 Dec;90:36-47.
    PMID: 25263930 DOI: 10.1016/j.phrs.2014.08.008
    Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins. Hematoxylin-eosin, periodic acid Schiff and Masson trichrome staining confirmed renal pathological changes in diabetic rats that included glomerular capsular wall distortion, mesangial cell expansion, glomerular microvascular condensation, tubular damage and degeneration and fibrosis. Low-dose fenofibrate (30mg/kg, p.o., 4 weeks) and low-dose dipyridamole (20mg/kg, p.o., 4 weeks) treatment either alone or in combination considerably reduced renal structural and functional abnormalities in diabetic rats, but without affecting the elevated glucose level. Fenofibrate, but not dipyridamole, significantly prevented the lipid alteration and importantly the uric acid elevation in diabetic rats. Lisinopril (5mg/kg, p.o., 4 weeks, reference compound), prevented the hyperglycemia, lipid alteration and development of diabetic nephropathy. Lipid alteration and uric acid elevation, besides hyperglycemia, could play key roles in the development of nephropathy. Low-doses of fenofibrate and dipyridamole treatment either alone or in combination markedly prevented the diabetes-induced nephropathy. Their combination was as effective as to their individual treatment, but not superior in preventing the development of diabetic nephropathy.
    Matched MeSH terms: Rats, Sprague-Dawley
  19. Fulltext Chemopreventive evaluation of a Schiff base derived copper (II) complex against azoxymethane-induced colorectal cancer in rats
    Hajrezaie M, Hassandarvish P, Moghadamtousi SZ, Gwaram NS, Golbabapour S, Najihussien A, et al.
    PLoS One, 2014;9(3):e91246.
    PMID: 24618844 DOI: 10.1371/journal.pone.0091246
    Based on the potential of Schiff base compounds to act as sources for the development of cancer chemotherapeutic agents, this in vivo study was performed to investigate the inhibitory properties of the synthetic Schiff base compound Cu(BrHAP)2 on colonic aberrant crypt foci (ACF).
    Matched MeSH terms: Rats
  20. Bone regeneration performance of surface-treated porous titanium
    Amin Yavari S, van der Stok J, Chai YC, Wauthle R, Tahmasebi Birgani Z, Habibovic P, et al.
    Biomaterials, 2014 Aug;35(24):6172-81.
    PMID: 24811260 DOI: 10.1016/j.biomaterials.2014.04.054
    The large surface area of highly porous titanium structures produced by additive manufacturing can be modified using biofunctionalizing surface treatments to improve the bone regeneration performance of these otherwise bioinert biomaterials. In this longitudinal study, we applied and compared three types of biofunctionalizing surface treatments, namely acid-alkali (AcAl), alkali-acid-heat treatment (AlAcH), and anodizing-heat treatment (AnH). The effects of treatments on apatite forming ability, cell attachment, cell proliferation, osteogenic gene expression, bone regeneration, biomechanical stability, and bone-biomaterial contact were evaluated using apatite forming ability test, cell culture assays, and animal experiments. It was found that AcAl and AnH work through completely different routes. While AcAl improved the apatite forming ability of as-manufactured (AsM) specimens, it did not have any positive effect on cell attachment, cell proliferation, and osteogenic gene expression. In contrast, AnH did not improve the apatite forming ability of AsM specimens but showed significantly better cell attachment, cell proliferation, and expression of osteogenic markers. The performance of AlAcH in terms of apatite forming ability and cell response was in between both extremes of AnH and AsM. AcAl resulted in significantly larger volumes of newly formed bone within the pores of the scaffold as compared to AnH. Interestingly, larger volumes of regenerated bone did not translate into improved biomechanical stability as AnH exhibited significantly better biomechanical stability as compared to AcAl suggesting that the beneficial effects of cell-nanotopography modulations somehow surpassed the benefits of improved apatite forming ability. In conclusion, the applied surface treatments have considerable effects on apatite forming ability, cell attachment, cell proliferation, and bone ingrowth of the studied biomaterials. The relationship between these properties and the bone-implant biomechanics is, however, not trivial.
    Matched MeSH terms: Rats, Wistar
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