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  1. Fulltext Defatted Kenaf (Hibiscus cannabinus L.) Seed Meal and Its Phenolic-Saponin-Rich Extract Protect Hypercholesterolemic Rats against Oxidative Stress and Systemic Inflammation via Transcriptional Modulation of Hepatic Antioxidant Genes
    Chan KW, Ismail M, Mohd Esa N, Mohamed Alitheen NB, Imam MU, Ooi J, et al.
    Oxid Med Cell Longev, 2018;2018:6742571.
    PMID: 29849908 DOI: 10.1155/2018/6742571
    The present study aimed to investigate the antioxidant and anti-inflammatory properties of defatted kenaf seed meal (DKSM) and its phenolic-saponin-rich extract (PSRE) in hypercholesterolemic rats. Hypercholesterolemia was induced using atherogenic diet feeding, and dietary interventions were conducted by incorporating DKSM (15% and 30%) or PSRE (at 2.3% and 4.6%, resp., equivalent to the total content of DKSM-phenolics and saponins in the DKSM groups) into the atherogenic diets. After ten weeks of intervention, serum total antioxidant capacities of hypercholesterolemic rats were significantly enhanced by DKSM and PSRE supplementation (p < 0.05). Similarly, DKSM and PSRE supplementation upregulated the hepatic mRNA expression of antioxidant genes (Nrf2, Sod1, Sod2, Gsr, and Gpx1) of hypercholesterolemic rats (p < 0.05), except for Gpx1 in the DKSM groups. The levels of circulating oxidized LDL and proinflammatory biomarkers were also markedly suppressed by DKSM and PSRE supplementation (p < 0.05). In aggregate, DKSM and PSRE attenuated the hypercholesterolemia-associated oxidative stress and systemic inflammation in rats, potentially by enhancement of hepatic endogenous antioxidant defense via activation of the Nrf2-ARE pathway, which may be contributed by the rich content of phenolics and saponins in DKSM and PSRE. Hence, DKSM and PSRE are prospective functional food ingredients for the potential mitigation of atherogenic risks in hypercholesterolemic individuals.
    Matched MeSH terms: Rats, Sprague-Dawley
  2. Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats
    Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X
    Drug Dev Res, 2019 09;80(6):837-845.
    PMID: 31301179 DOI: 10.1002/ddr.21567
    The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.
    Matched MeSH terms: Rats, Sprague-Dawley
  3. Fulltext Anti-ulcerogenic activity of dentatin from clausena excavata Burm.f. against ethanol-induced gastric ulcer in rats: Possible role of mucus and anti-oxidant effect
    Sidahmed HMA, Vadivelu J, Loke MF, Arbab IA, Abdul B, Sukari MA, et al.
    Phytomedicine, 2019 Mar 01;55:31-39.
    PMID: 30668441 DOI: 10.1016/j.phymed.2018.06.036
    BACKGROUND: Clausena excavata Burm.f. (Rutaceae) has been used for the treatment of stomach disorders including peptic ulcer.

    PURPOSE: In this study, we aimed to investigate dentatin isolated from C. excavata Burm.f., for anti-ulcer activity against ethanol ulcer model in rats.

    METHODS: Gastric acid output, ulcer index, serum profile, histological evaluation using Hematoxylin and eosin (HE), periodic acid Schiff base stainings and immunohistochemical localization for heat shock proteins 70 (HSP70) were all investigated. Possible involvement of reduced glutathione (GSH), lipid peroxidation, prostaglandin E2 (PGE2), superoxide dismutase (SOD) enzymes, radical scavenging, and anti-Helicobacter pylori activity were investigated.

    RESULTS: Dentatin showed anti-secretory activity against the pylorus ligature model and protected the gastric mucosa from ethanol ulceration, as revealed by the improved macroscopic and histological appearance. Dentatin significantly increased the gastric homogenate content of PGE2 GSH and SOD. Dentatin inhibited the lipid peroxidation as revealed by the reduced gastric content of malondialdehyde (MDA). Moreover, dentatin up-regulated HSP70 expression. However, dentatin showed insignificant anti-H. pylori activity.

    CONCLUSION: Dentatin possesses gastro-protective activity, which could be attributed to the anti-secretory, mucus production, anti-oxidant, and HSP70 activities.

    Matched MeSH terms: Rats, Sprague-Dawley
  4. Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level
    Fakurazi S, Hairuszah I, Nanthini U
    Food Chem Toxicol, 2008 Aug;46(8):2611-5.
    PMID: 18514995 DOI: 10.1016/j.fct.2008.04.018
    Initiation of acetaminophen (APAP) toxicities is believed to be promoted by oxidative stress during the event of overdosage. The aim of the present study was to evaluate the hepatoprotective action of Moringa oleifera Lam (MO), an Asian plant of high medicinal value, against a single high dose of APAP. Groups of five male Sprague-Dawley rats were pre-administered with MO (200 and 800 mg/kg) prior to a single dose of APAP (3g/kg body weight; p.o). Silymarin was used as an established hepatoprotective drug against APAP induced liver injury. The hepatoprotective activity of MO extract was observed following significant histopathological analysis and reduction of the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in groups pretreated with MO compared to those treated with APAP alone. Meanwhile, the level of glutathione (GSH) was found to be restored in MO-treated animals compared to the groups treated with APAP alone. These observations were comparable to the group pretreated with silymarin prior to APAP administration. Group that was treated with APAP alone exhibited high level of transaminases and ALP activities besides reduction in the GSH level. The histological hepatocellular deterioration was also evidenced. The results from the present study suggested that the leaves of MO can prevent hepatic injuries from APAP induced through preventing the decline of glutathione level.
    Matched MeSH terms: Rats, Sprague-Dawley
  5. Absorption of andrographolides from Andrographis paniculata and its effect on CCl(4)-induced oxidative stress in rats
    Akowuah GA, Zhari I, Mariam A, Yam MF
    Food Chem Toxicol, 2009 Sep;47(9):2321-6.
    PMID: 19540299 DOI: 10.1016/j.fct.2009.06.022
    A simple and validated high-performance liquid chromatography (HPLC) method with UV detection has been used to determine the content of andrographolide (AP) and 14-deoxy-11,12-didehydroandrographolide (DIAP) in rat plasma after oral dose of methanol extract (1 g/kg body weight) of Andrographis paniculata leaf. An increase in plasma concentration of AP and DIAP was observed from 30 min to 3 h after oral administration of the extract. The maximum plasma concentrations of AP and DIAP were 1.42+/-0.09 microg/ml and 1.31+/-0.04 microg/ml, respectively. Fourteen days oral treatment of rats with the methanol extract (1 g/kg body weight) followed by CCl(4) administration preserved catalase (CAT), and superoxide dismutase (SOD) activities in erythrocytes, whereas plasma lipid peroxidation, alanine transaminase (ALT) and aspartate transaminase (AST) activities were restored to values comparable with control values. Treatment of rats with CCl(4) did not showed significant alteration (p>0.05) in plasma total antioxidant status (TAS) as compare to values of control group.
    Matched MeSH terms: Rats, Sprague-Dawley
  6. The methanolic fraction of Centratherum anthelminticum seed downregulates pro-inflammatory cytokines, oxidative stress, and hyperglycemia in STZ-nicotinamide-induced type 2 diabetic rats
    Arya A, Cheah SC, Looi CY, Taha H, Mustafa MR, Mohd MA
    Food Chem Toxicol, 2012 Nov;50(11):4209-20.
    PMID: 22939938 DOI: 10.1016/j.fct.2012.08.012
    This study aimed to ascertain the potential of Centratherum anthelminticum seeds methanolic fraction (CAMFs) for the management of type 2 diabetes and its associated complications. CAMFs was initially tested on β-TC6 cells for H(2)O(2)-induced nuclear factor-κB (NF-κB) translocation effects. The result displayed that CAMFs significantly inhibited NF-κB translocation from cytoplasm into the nucleus, dose-dependently. Furthermore, a 12-week sub-chronic CAMFs study was carried out on streptozotocin (STZ)-nicotinamide-induced type 2 diabetic rat model to evaluate glycemia, essential biochemical parameters, lipid levels, oxidative stress markers, and pro-inflammatory cytokines level. Our study result showed that CAMFs reduced hyperglycemia by increasing serum insulin, C-peptide, total protein, and albumin levels, significantly. Whereas, elevated blood glucose, glycated hemoglobin, lipids and enzyme activities were restored to near normal. CAMFs confirmed antioxidant potential by elevating glutathione (GSH) and reducing malondialdehyde (MDA) levels in diabetic rats. Interestingly, CAMFs down-regulated elevated tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the tissues and serum of the diabetic rats. We conclude that CAMFs exerted apparent antidiabetic effects and demonstrated as a valuable candidate nutraceutical for insulin-resistant type 2 diabetes and its associated complications such as dyslipidemia, oxidative stress, and inflammation.
    Matched MeSH terms: Rats, Sprague-Dawley
  7. Diazinon-induced oxidative stress and renal dysfunction in rats
    Shah MD, Iqbal M
    Food Chem Toxicol, 2010 Dec;48(12):3345-53.
    PMID: 20828599 DOI: 10.1016/j.fct.2010.09.003
    Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphoro thioate), an organo-phosphate insecticide, has been used worldwide in agriculture and domestic for several years, which has led to a variety of negative effects in non target species including humans. However, its nephrotoxic effects and mechanism of action has not been fully elucidated so far. Therefore, the present study was aimed at evaluating the nephrotoxic effects of diazinon and its mechanism of action with special reference to its possible ROS generating potential in rats. Treatment of rats with diazinon significantly enhances renal lipid peroxidation which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidise, glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione S-transferase) and depletion in the level of glutathione reduced. In contrast, the activities of renal γ-glutamyl transpeptidase and quinone reductase were increased. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen and serum creatinine. Additionally, the impairment of renal function corresponds histopathologically. In summary, our results indicate that diazinon treatment eventuates in decreased renal glutathione reduced, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.
    Matched MeSH terms: Rats, Sprague-Dawley
  8. Protective effects of Etlingera elatior extract on lead acetate-induced changes in oxidative biomarkers in bone marrow of rats
    Haleagrahara N, Jackie T, Chakravarthi S, Rao M, Pasupathi T
    Food Chem Toxicol, 2010 Oct;48(10):2688-94.
    PMID: 20600524 DOI: 10.1016/j.fct.2010.06.041
    Several environmental toxins with toxic effects to the bone marrow have been identified. Pathology associated with lead intoxication is due to the cellular damage mediated by free radicals. In the current study, we examined the effect of Etlingera elatior extract on lead-induced changes in the oxidative biomarkers and histology of bone marrow of rats. Sprague-Dawley rats were exposed to 500 ppm lead acetate in their drinking water for 14 days. E. elatior extract was treated orally (100mg/kg body weight) in combination with, or after lead acetate treatment. The results showed that there was a significant increase in lipid hydroperoxide, protein carbonyl content and a significant decrease in total antioxidants, super oxide dismutase, glutathione peroxidase and glutathione--S-transferase in bone marrow after lead acetate exposure. Treatment with E. elatior decreased lipid hydroperoxides and protein carbonyl contents and significantly increased total antioxidants and antioxidant enzymes. Treatments with E. elatior extract also reduced, lead-induced histopathological damage in bone marrow. In conclusion, these data suggest that E. elatior has a powerful antioxidant effect, and it protects the lead acetate-induced bone marrow oxidative damage in rats.
    Matched MeSH terms: Rats, Sprague-Dawley
  9. N-acetylcysteine offers cardioprotection by decreasing cardiac lipid hydroperoxides and 8-isoprostane level in isoproterenol-induced cardiotoxicity in rats
    Haleagrahara N, Julian V, Chakravarthi S
    Cardiovasc Toxicol, 2011 Dec;11(4):373-81.
    PMID: 21796404 DOI: 10.1007/s12012-011-9132-0
    This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague-Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P 
    Matched MeSH terms: Rats, Sprague-Dawley
  10. Fulltext No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats
    Hong YH, Betik AC, Premilovac D, Dwyer RM, Keske MA, Rattigan S, et al.
    Am J Physiol Regul Integr Comp Physiol, 2015 May 15;308(10):R862-71.
    PMID: 25786487 DOI: 10.1152/ajpregu.00412.2014
    Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.
    Matched MeSH terms: Rats, Sprague-Dawley
  11. Fulltext The Efficacy of Processing Strategies on the Gastroprotective Potentiality of Chenopodium quinoa Seeds
    Mariod AA, Salama SM
    ScientificWorldJournal, 2020;2020:6326452.
    PMID: 32549800 DOI: 10.1155/2020/6326452
    The current study has been conducted to evaluate the effect of different processing techniques on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and the gastroprotective potential of Chenopodium quinoa red seeds in acute gastric injury induced by absolute ethanol in rats. Seven groups of female Sprague Dawley rats were assigned to normal and absolute ethanol (absolute EtOH) groups, given distilled water, reference control omeprazole (OMP, 20 mg/kg), pressure-cooked quinoa seeds (QP, 200 mg/kg), first stage-germinated quinoa seeds (QG, 200 mg/kg), Lactobacillus plantarum bacteria-fermented quinoa seeds (QB, 200 mg/kg), and Rhizopus oligosporus fungus-fermented quinoa seeds (QF, 200 mg/kg). One hour after treatment, all groups were given absolute ethanol, except for the normal control rats. All animals were sacrificed after an additional hour, and the stomach tissues were examined for histopathology of hematoxylin and eosin staining, immunohistochemistry of cyclooxygenase 2 (COX-2), and nitric oxide synthase (iNOS). Stomach homogenates were evaluated for oxidative stress parameters and prostaglandin E2 (PGE2). Gene expression was performed for gastric tumor necrosis factor alpha (TNF-α) and nuclear factor kappa of B cells (NF-kB). QB and QG recorded the highest DPPH scavengers compared to QF and QP. The gastroprotective potential of QB was comparable to that of OMP, followed by QF, then QG, and QP as confirmed by the histopathology, immunohistochemistry, and gene expression assessments. In conclusion, differently processed red quinoa seeds revealed variable antioxidant capacity and gastroprotective potential, while the bacterial fermented seeds (QB) showed the highest potential compared to the other processing techniques. These results might offer promising new therapy in the treatment of acute gastric injury.
    Matched MeSH terms: Rats, Sprague-Dawley
  12. Fulltext Hepatoprotective Effect of Supercritical Carbon Dioxide Extracted Dabai Pulp Oil and Its Defatted Pulp
    Kadir NAAA, Azlan A, Abas F, Ismail IS
    Molecules, 2021 Jan 28;26(3).
    PMID: 33525363 DOI: 10.3390/molecules26030671
    All food scientists must utilize plants for their application as functional foods to reduce hypercholesterolemia incidence through diet. Canarium odontophyllum (dabai) is a novel source for new healthy oil and functional foods. In this work, we evaluate the hepatoprotective effects of supercritical carbon dioxide (SC-CO2) extracted dabai pulp oil (DPO) and defatted dabai pulp (DDP) against hypercholesterolemia elicited by a high-cholesterol diet in rats. Our results show that DPO and DDP supplementation exerted beneficial hypocholesterolemic effects against the high-cholesterol diet-fed rat. Nevertheless, supplementation with DDP revealed superior total cholesterol, low-density lipoprotein, and HMG-CoA reductase lowering efficacy (p < 0.05). Supplementation of either DPO or DDP did not significantly affect AST and ALT levels than normal rats (p > 0.05). Therefore, DDP and DPO are considered as having no toxicological significance. The histological section of rats treated with DPO and DDP showed improved steatosis in hepatocytes. HPLC analysis revealed that DPO and DDP contained syringic acid, which plays an important role in the beneficial effect. In conclusion, our results support the hypocholesterolemic and hepatoprotective effects of DPO and DDP in the hypercholesterolemic rats model.
    Matched MeSH terms: Rats, Sprague-Dawley
  13. Fulltext Differential Action of Connexin Hemichannel and Pannexin Channel Therapeutics for Potential Treatment of Retinal Diseases
    Mat Nor MN, Rupenthal ID, Green CR, Acosta ML
    Int J Mol Sci, 2021 Feb 10;22(4).
    PMID: 33578721 DOI: 10.3390/ijms22041755
    Dysregulation of retinal function in the early stages of light-induced retinal degeneration involves pannexins and connexins. These two types of proteins may contribute to channels that release ATP, leading to activation of the inflammasome pathway, spread of inflammation and retinal dysfunction. However, the effect of pannexin channel block alone or block of both pannexin channels and connexin hemichannels in parallel on retinal activity in vivo is unknown. In this study, the pannexin channel blocker probenecid and the connexin hemichannel blocker tonabersat were used in the light-damaged rat retina. Retinal function was evaluated using electroretinography (ERG), retinal structure was analyzed using optical coherence tomography (OCT) imaging and the tissue response to light-induced injury was assessed immunohistochemically with antibodies against glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1 (Iba-1) and Connexin43 (Cx43). Probenecid did not further enhance the therapeutic effect of connexin hemichannel block in this model, but on its own improved activity of certain inner retina neurons. The therapeutic benefit of blocking connexin hemichannels was further evaluated by comparing these data against results from our previously published studies that also used the light-damaged rat retina model. The analysis showed that treatment with tonabersat alone was better than probenecid alone at restoring retinal function in the light-damaged retina model. The results assist in the interpretation of the differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases.
    Matched MeSH terms: Rats, Sprague-Dawley
  14. Fulltext Functional subtypes of renal alpha1-adrenoceptor in diabetic and non-diabetic 2K1C Goldblatt renovascular hypertension
    Armenia A, Sattar MA, Abdullah NA, Khan MA, Johns EJ
    Acta Pharmacol Sin, 2008 May;29(5):564-72.
    PMID: 18430364 DOI: 10.1111/j.1745-7254.2008.00788.x
    This study investigates the subtypes of the alpha1-adrenoceptor mediating the adrenergically-induced renal vasoconstrictor responses in streptozotocin-induced diabetic and non-diabetic 2-kidney one clip (2K1C) Goldblatt hypertensive rats.
    Matched MeSH terms: Rats, Sprague-Dawley
  15. Neuroprotective effect of poly(lactic-co-glycolic acid) nanoparticle-bound brain-derived neurotrophic factor in a permanent middle cerebral artery occlusion model of ischemia in rats
    Kamarudin SN, Iezhitsa I, Tripathy M, Alyautdin R, Ismail NM
    Acta Neurobiol Exp (Wars), 2020;80(1):1-18.
    PMID: 32214270
    Poly (lactide‑co‑glycolide) (PLGA) nanoparticles (NPs) are biodegradable carriers that participate in the transport of neuroprotective drugs across the blood brain barrier (BBB). Targeted brain‑derived neurotrophic factor (BDNF) delivery across the BBB could provide neuroprotection in brain injury. We tested the neuroprotective effect of PLGA nanoparticle‑bound BDNF in a permanent middle cerebral artery occlusion (pMCAO) model of ischemia in rats. Sprague‑Dawley rats were subjected to pMCAO. Four hours after pMCAO, two groups were intravenously treated with BDNF and NP‑BDNF, respectively. Functional outcome was assessed at 2 and 24 h after pMCAO, using the modified neurologic severity score (mNSS) and rotarod performance tests. Following functional assessments, rats were euthanized blood was taken to assess levels of the neurobiomarkers neuron‑specific enolase and S100 calcium‑binding protein β (S100β), and the brain was evaluated to measure the infarct volume. The NP‑BDNF‑treated group showed significant improvement in mNSS compared with pMCAO and BDNF‑treated groups and showed improved rotarod performance. The infarct volume in rats treated with NP‑BDNFs was also significantly smaller. These results were further corroborated by correlating differences in estimated NSE and S100β. NP‑BDNFs exhibit a significant neuroprotective effect in the pMCAO model of ischemia in rats.
    Matched MeSH terms: Rats, Sprague-Dawley
  16. Palmatine Inhibits Up-Regulation of GRP78 and CALR Protein in an STZ-Induced Diabetic Rat Model
    Okechukwu PN, Ekeuku SO, Chan HK, Eluri K, Froemming GRA
    Curr Pharm Biotechnol, 2021;22(2):288-298.
    PMID: 32744968 DOI: 10.2174/1389201021666200730124208
    BACKGROUND: Diabetes Mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) which is due to the destruction of insulin-producing β-cells in the islets of Langerhans in the pancreas. It is associated with oxidative and endoplasmic reticulum stress. The plant alkaloid Palmatine has been previously reported to possess antidiabetic and antioxidant properties as well as other protective properties against kidney and liver tissue damage.

    OBJECTIVE: Here, we investigated the ability of Palmatine to reduce the up-regulation of chaperone proteins Glucose Regulatory Protein 78 (GRP78), and Calreticulin (CALR) protein in a Streptozotocin (STZ)-induced diabetic rat model.

    METHODS: Streptozotocin (STZ) induced diabetes in Sprague Dawley rats treated with 2mg/kg of Palmatine for 12 weeks after the elevation of plasma glucose levels above 11mmol/L post-STZ administration. Proteins were extracted from the pancreas after treatment and Two-Dimensional gel electrophoresis (2-DE), PDQuest 2-D analysis software genomic solutions and mass spectrometer were used to analyze differentially expressed protein. Mass Spectrometry (MS/MS), Multidimensional Protein Identification Technology (MudPIT) was used for protein identification.

    RESULTS: There was an up-regulation of the expression of chaperone proteins CALR and GRP78 and down-regulation of the expression of antioxidant and protection proteins peroxidoxin 4 (Prdx4), protein disulfide isomerase (PDIA2/3), Glutathione-S-Transferase (GSTs), and Serum Albumin (ALB) in non-diabetic rats. Palmatine treatment down-regulated the expression of chaperone proteins CALR and GRP78 and up-regulated the expression of Prdx4, PDIA2/3, GST, and ALB.

    CONCLUSION: Palmatine may have activated antioxidant proteins, which protected the cells against reactive oxygen species and endoplasmic stress. The result is in consonance with our previous report on Palmatine.

    Matched MeSH terms: Rats, Sprague-Dawley
  17. The molecular mechanisms of probiotic strains in improving ageing bone and muscle of d-galactose-induced ageing rats
    Hor YY, Ooi CH, Lew LC, Jaafar MH, Lau AS, Lee BK, et al.
    J Appl Microbiol, 2021 Apr;130(4):1307-1322.
    PMID: 32638482 DOI: 10.1111/jam.14776
    AIM: The aim of this study was to evaluate the molecular mechanisms of Lactobacillus strains in improving ageing of the musculoskeletal system.

    METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P 

    Matched MeSH terms: Rats, Sprague-Dawley
  18. Fulltext Mikania micrantha Extract Inhibits HMG-CoA Reductase and ACAT2 and Ameliorates Hypercholesterolemia and Lipid Peroxidation in High Cholesterol-Fed Rats
    Ibrahim A, Shafie NH, Mohd Esa N, Shafie SR, Bahari H, Abdullah MA
    Nutrients, 2020 Oct 09;12(10).
    PMID: 33050310 DOI: 10.3390/nu12103077
    The present study aimed to determine the effect of an ethyl acetate extract of Mikania micrantha stems (EAMMS) in hypercholesterolemia-induced rats. Rats were divided into a normal group (NC) and hypercholesterolemia induced groups: hypercholesterolemia control group (PC), simvastatin group (SV) (10 mg/kg) and EAMMS extract groups at different dosages of 50, 100 and 200 mg/kg, respectively. Blood serum and tissues were collected for haematological, biochemical, histopathological, and enzyme analysis. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, malondialdehyde (MDA) level, as well as enzymes of HMG-CoA reductase (HMGCR) and acetyl-CoA acetyltransferase 2 (ACAT2), were measured. Feeding rats with high cholesterol diet for eight weeks resulted in a significantly (p < 0.05) increased of TC, TG, LDL-C, AST, ALT and MDA levels. Meanwhile, the administration of EAMMS extract (50, 100 and 200 mg/kg) and simvastatin (10 mg/kg) significantly reduced (p < 0.05) the levels of TC, TG, LDL-C and MDA compared to rats in the PC group. Furthermore, all EAMMS and SV-treated groups showed a higher HDL-C level compared to both NC and PC groups. No significant difference was found in the level of ALT, AST, urea and creatinine between the different dosages in EAMMS extracts. Treatment with EAMMS also exhibited the highest inhibition activity of enzyme HMGCR and ACAT2 as compared to the control group. From the histopathological examination, liver tissues in the PC group showed severe steatosis than those fed with EAMMS and normal diet. Treatment with EAMMS extract ameliorated and reduced the pathological changes in the liver. No morphological changes showed in the kidney structure of both control and treated groups. In conclusion, these findings demonstrated that EAMMS extract has anti-hypercholesterolemia properties and could be used as an alternative treatment for this disorder.
    Matched MeSH terms: Rats, Sprague-Dawley
  19. Fulltext Clinacanthus nutans Leaves Extract Reverts Endothelial Dysfunction in Type 2 Diabetes Rats by Improving Protein Expression of eNOS
    Azemi AK, Mokhtar SS, Rasool AHG
    Oxid Med Cell Longev, 2020;2020:7572892.
    PMID: 32879653 DOI: 10.1155/2020/7572892
    Diabetes mellitus is associated with endothelial dysfunction; it causes progressive vascular damage resulting from an impaired endothelium-dependent vasorelaxation. In the diabetes state, presence of hyperglycemia and insulin resistance predisposes to endothelial dysfunction. Clinacanthus nutans, widely used as a traditional medicine for diabetes is reported to have hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory properties. However, the possibility of C. nutans affecting the vascular endothelial function in diabetes remains unclear. This study was aimed at evaluating the effects of C. nutans methanolic leaves extract (CNME) on endothelial function in a type 2 diabetes (T2DM) rat model. Sixty male Sprague-Dawley rats were divided into five groups (n = 12 per group): nondiabetic control, nondiabetic treated with four weeks of CNME (500 mg/kg/daily), untreated diabetic rats, diabetic treated with metformin (300 mg/kg/daily), and diabetic treated with CNME (500 mg/kg/daily). T2DM was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) to rats fed with high-fat diet (HFD). Endothelial-dependent and endothelial-independent relaxations and contractions of the thoracic aorta were determined using the organ bath. Aortic endothelial nitric oxide synthase (eNOS) expression was determined using Western blotting. Endothelial-dependent relaxation was reduced in diabetic rats. Both diabetic groups treated with CNME or metformin significantly improved the impairment in endothelium-dependent vasorelaxation; this was associated with increased expression of aortic eNOS protein. CNME- and metformin-treated groups also reduced aortic endothelium-dependent and aortic endothelium-independent contractions in diabetics. Both of these diabetic-treated groups also reduced blood glucose levels and increased body weight compared to the untreated diabetic group. In conclusion, C. nutans improves endothelial-dependent vasodilatation and reduces endothelial-dependent contraction, thus ameliorating endothelial dysfunction in diabetic rats. This may occur due to its effect on increasing eNOS protein expression.
    Matched MeSH terms: Rats, Sprague-Dawley
  20. Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function
    Parker LM, Damanhuri HA, Fletcher SP, Goodchild AK
    Brain Res, 2015 Apr 16;1604:25-34.
    PMID: 25662772 DOI: 10.1016/j.brainres.2015.01.049
    Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.
    Matched MeSH terms: Rats, Sprague-Dawley
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