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  1. The effect of intravenous infusion of L-arginine, glycine and D-lysine on urinary calcium excretion in the rat
    Singh HJ
    Jpn. J. Physiol., 1995;45(2):327-36.
    PMID: 7563967
    Standard renal clearance techniques were used to compare the effects of intravenous infusions of L-arginine, D-lysine and glycine on urinary calcium excretion in the rat. A significant calciuric response was evident following the infusion of all three amino acids in all the animals. The maximal effect was evident in rats receiving L-arginine. The mechanism for the increased urinary calcium excretion in rats infused with L-arginine and D-lysine appeared more due to a decreased fractional reabsorption of this cation as no significant changes in the glomerular filtration rate (GFR) were evident in these two groups. The calciuria in rats receiving glycine appears due to increased filtered load secondary to the increased GFR, suggesting that the mechanism for calciuria evident following protein ingestion or amino acid infusion may vary and may be dependent upon the amino acid ingested or infused.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  2. Effect of dietary palm oils on mammary carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene
    Sundram K, Khor HT, Ong AS, Pathmanathan R
    Cancer Res, 1989 Mar 15;49(6):1447-51.
    PMID: 2493981
    Female Sprague-Dawley rats, 50 days of age, were treated with a single dose of 5 mg of 7,12-dimethylbenz(a)anthracene intragastrically. 3 days after carcinogen treatment, the rats were put on semisynthetic diets containing 20% by weight of corn oil (CO), soybean oil (SBO), crude palm oil (CPO), refined, bleached, deodorized palm oil (RBD PO) and metabisulfite-treated palm oil (MCPO) for 5 months. During the course of experiments, rats fed on different dietary fats had similar rate of growth. Rats fed 20% CO or SBO diet have higher tumor incidence than rats fed on palm oil (PO) diets; however differences of mean tumor latency periods among the groups were not statistically significant. At autopsy, rats fed on high CO or SBO diets had significantly more tumors than rats fed on the three PO diets. Our results showed that high PO diets did not promote chemically induced mammary tumorigenesis in female rats when compared to high CO or SBO diets. CO and SBO differ greatly from the palm oils in their contents of tocopherols, tocotrienols, and carotenes. But further experiments would be required to determine whether the observed differences in tumor incidence and tumor numbers were due to the differences in these minor components or due to the unique triglyceride structure of the palm oils. Analysis of the fatty acid profiles of plasma total lipids of tumor-bearing rats and of the tumor total lipids showed that, with the exception of arachidonic acid, the fatty acid profiles reflect the nature of the dietary fats. At autopsy, there were no differences in the plasma total cholesterol contents among rats fed on different dietary fats, but rats fed on palm oil diets had a significantly higher plasma triglyceride level than that of rats fed CO or SBO diets. As for the tumor lipids, there were no significant differences in the triglyceride, diglyceride, and phospholipid levels when the CO or SBO groups were compared to the palm oil groups.
    Matched MeSH terms: Rats, Inbred Strains; Rats
  3. Inhibition of rat testicular microsomal steroidogenesis by oxytocin and metyrapone
    Kwan TK, Gower DB
    Biochem. Int., 1988 Apr;16(4):629-37.
    PMID: 3390195
    Capillary gas chromatographic 'steroid profiling' has been utilised to separate and quantify the metabolites (derivatized as methyloximes and/or trimethylsilyl ethers) formed from pregnenolone after incubation with rat testicular microsomes. A wide range of steroid metabolites was found, indicating that both the 5-ene and 4-ene pathways of testosterone biosynthesis were operating, as well as 16 alpha-hydroxylation, 20 beta-reduction and the formation of several C19 steroids (the 16-androstenes). At the concentration used, Metyrapone markedly inhibited 16 alpha- and 17-hydroxylation and side-chain cleavage of 17-hydroxylated C21 steroids. 16-Androstene production was also markedly inhibited and the formation of other metabolites was affected to lesser extents. Oxytocin abolished the formation of all C21 and C19 metabolites of pregnenolone.
    Matched MeSH terms: Rats, Inbred Strains; Rats
  4. Steroid profiling in the study of rat testicular steroidogenesis
    Kwan TK, Pertiwi AK, Taylor NF, Gower DB
    Biochim. Biophys. Acta, 1988 Sep 23;962(2):214-9.
    PMID: 3167079
    Twenty authentic steroids, derivatized as O-methyl oximes (MO), trimethylsilyl (TMS) ethers or as MO-TMS ethers have been subjected to capillary gas chromatography using two different columns. Virtually all of the steroid derivatives have been resolved, one difficult pair to separate being 5,16-androstadien-3 beta-ol and 5 alpha-androst-16-en-3 beta-ol on the non-selective phase OV-1. Where syn and anti forms of MO derivatives arose, these were also resolved under the conditions utilised. This technique of 'steroid profiling' has been applied to the separation and quantification of metabolites of pregnenolone which were formed during incubations of the microsomal and cytosolic fractions from rat testes. The majority of the metabolites were found in the microsomal incubation. These compounds included some odorous 16-androstenes as well as other C21 and C19 steroids, the formation of which was consistent with the 5-ene and 4-ene pathways of testosterone biosynthesis being operative. In addition, evidence was obtained for 16 alpha-hydroxylation of C21 steroids. Very much less metabolic activity was found in the cytosolic fraction of rat testes. Metabolic pathways have been proposed which both confirm and extend earlier work. We conclude that the rat testis can only form some of the odorous, possibly pheromonal, 16-androstenes and that these are quantitatively less important than in the porcine testis.
    Matched MeSH terms: Rats, Inbred Strains; Rats
  5. Vasorelaxation induced by common edible tropical plant extracts in isolated rat aorta and mesenteric vascular bed
    Runnie I, Salleh MN, Mohamed S, Head RJ, Abeywardena MY
    J Ethnopharmacol, 2004 Jun;92(2-3):311-6.
    PMID: 15138017
    In this study, the vasodilatory actions of nine edible tropical plant extracts were investigated. Ipomoea batatas (sweet potato leaf), Piper betle (betel leaf), Anacardium occidentale (cashew leaf), Gynandropsis gynandra (maman leaf), Carica papaya (papaya leaf), and Mentha arvensis (mint leaf) extracts exhibited more than 50% relaxing effect on aortic ring preparations, while Piper betle and Cymbopogon citratus (lemongrass stalk) showed comparable vasorelaxation on isolated perfused mesenteric artery preparation. The vascular effect on the aortic ring preparations were mainly endothelium-dependent, and mediated by nitric oxide (NO) as supported by the inhibition of action in the presence of N(omega)-nitro-L-arginine (NOLA), an nitric oxide synthase (NOS) inhibitor, or by the removal of endothelium. In contrast, vasodilatory actions in resistance vessels (perfused mesenteric vascular beds) appear to involve several biochemical mediators, including NO, prostanoids, and endothelium-dependent hyperpolarizing factors (EDHFs). Total phenolic contents and antioxidant capacities varied among different extracts and found to be independent of vascular relaxation effects. This study demonstrates that many edible plants common in Asian diets to possess potential health benefits, affording protection at the vascular endothelium level.
    Matched MeSH terms: Rats, Inbred WKY; Rats
  6. Fulltext Hippocampal amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluA1 (AMPA GluA1) receptor subunit involves in learning and memory improvement following treatment with Centella asiatica extract in adolescent rats
    Binti Mohd Yusuf Yeo NA, Muthuraju S, Wong JH, Mohammed FR, Senik MH, Zhang J, et al.
    Brain Behav, 2018 09;8(9):e01093.
    PMID: 30105867 DOI: 10.1002/brb3.1093
    INTRODUCTION: Centella asiatica is an herbal plant that contains phytochemicals that are widely believed to have positive effects on cognitive function. The adolescent stage is a critical development period for the maturation of brain processes that encompass changes in physical and psychological systems. However, the effect of C. asiatica has not been extensively studied in adolescents. The aim of this study was therefore to investigate the effects of a C. asiatica extract on the enhancement of learning and memory in adolescent rats.

    METHODS: The locomotor activity, learning, and memory were assessed by using open field test and water T-maze test. This study also examined changes in neuronal cell morphology using cresyl violet and apoptosis staining. We also performed immunohistochemical study to analyse the expression of the glutamate AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) GluA1 subunit and the GABA receptor (γ-Aminobutyric Acid) subtype GABAA α1 subunit in the hippocampus of the same animals.

    RESULTS: We found no significant changes in locomotor activity (p > 0.05). The water T-maze data showed that 30 mg/kg dose significantly (p  0.05). Histological data revealed no neuronal morphological changes. Immunohistochemical analysis revealed increased expression of the AMPA GluA1 receptor subunit but there was no effect on GABAA receptor α1 subunit expression in the CA1 and CA2 subregions of the hippocampus.

    CONCLUSIONS: The C. asiatica extract therefore improved hippocampus-dependent spatial learning and memory in a dose-dependent manner in rats through the GluA1-containing AMPA receptor in the CA1 and CA2 sub regions of the hippocampus.

    Matched MeSH terms: Rats, Wistar; Rats
  7. Fulltext Effects of calcium supplements on fracture healing in a rat osteoporotic model
    Shuid AN, Mohamad S, Mohamed N, Fadzilah FM, Mokhtar SA, Abdullah S, et al.
    J Orthop Res, 2010 Dec;28(12):1651-6.
    PMID: 20572125 DOI: 10.1002/jor.21180
    Fracture healing is a complex process, which is further complicated if the bone is osteoporotic. Calcium is one of the important minerals in bone and has been found to prevent osteoporosis but its role in fracture healing of osteoporotic bone is still unclear. We carried out a study on the effects of calcium supplementation on the late phase healing of fractured osteoporotic bone using an ovariectomized rat model. Twenty-four female Sprague-Dawley rats were divided into three groups: sham-operated (SO), ovariectomized-control (OVXC), and ovariectomized + calcium supplements (Ca). The right femurs of all the rats were fractured at mid-epiphysis and a K-wire was inserted for internal fixation. After 2 months of treatment, the rats were sacrificed and the femora were dissected out for radiological and biomechanical assessment. As expected, osteoporosis resulted in impaired healing as shown by the poor radiological and biomechanical properties of the OVXC group. CT scans showed significantly lower callus volumes in the SO and Ca groups compared to the OVXC group. Radiological scoring of fracture healing and callus staging of the SO and Ca groups were better than the OVXC group. However, the biomechanical parameters of the Ca group were significantly lower than the SO group and similar to the OVXC group. Therefore, calcium supplements may appear to improve fracture healing of osteoporotic bone but failed to improve strength.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  8. The effect of losartan and carvedilol on renal haemodynamics and altered metabolism in fructose-fed Sprague-Dawley rats
    Abdulla MH, Sattar MA, Abdullah NA, Johns EJ
    J Physiol Biochem, 2012 Sep;68(3):353-63.
    PMID: 22281695 DOI: 10.1007/s13105-012-0147-1
    The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  9. Short- and long-term effects of glycyrrhizic acid in repetitive stress
    Ainsah O, Nabishah BM, Osman CB, Khalid BA
    Clin Exp Pharmacol Physiol, 1999 7 1;26(5-6):444-8.
    PMID: 10386236
    1. This study was carried out to determine the effect of short-term and long-term ingestion of glycyrrhizic acid on the response to 2 h of restraint stress by measuring locomotor activity and plasma corticosterone levels. 2. Male Sprague-Dawley rats were randomly assigned into four groups, each group having eight rats. Group 1 (control) was given ordinary tap water, while groups 2 (short term), 3 and 4 (both long term) were given tap water containing 1 mg/mL glycyrrhizic acid to drink for 10 days, 4 weeks and 9 weeks, respectively. All the rats were subjected to 2 h of restraint stress and the locomotor activity assessed using an activity test in an open field arena followed by blood sampling to determine the plasma corticosterone level. These procedures were repeated daily for 14 days. 3. The basal locomotor activity scores for rats given glycyrrhizic acid for 10 days or 4 weeks were similar to those of controls; however, that of the rats treated long term with glycyrrhizic acid was significantly lower (21.0 +/- 3.0 squares crossed; P < 0.0005). Following the first period of restraint stress there was a highly significant decrease in locomotor activity, which remained significantly lower until the seventh and subsequent periods, indicating an adaptation to the repeated stress had occurred. Although the decrease in locomotor activity was partially blocked and adaptation to repetitive stress was enhanced in the rats given glycyrrhizic acid for 10 days, this was not seen in rats treated with glycyrrhizic acid for 4 or 9 weeks. The corticosterone levels in control rats were significantly elevated for 4-5 days following the exposure to repetitive stress but decreased gradually from day 7 onwards. However, both short- and long-term glycyrrhizic acid-treated rats had higher plasma corticosterone levels than the controls (P < 0.05). 4. In conclusion, repetitive restraint stress caused decreased locomotor activity associated with increased plasma corticosterone levels, both of which, in normal rats, decreased with adaptation to stress. The stress response was partially blocked and adaptation enhanced in rats given glycyrrhizic acid for 10 days, but not in rats given glycyrrhizic acid for 4 and 9 weeks. Glycyrrhizic acid ingestion caused high plasma corticosterone.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  10. Purified ingredient-based high-fat diet is superior to chow-based equivalent in the induction of metabolic syndrome
    Cheng HS, Phang SCW, Ton SH, Abdul Kadir K, Tan JBL
    J Food Biochem, 2019 02;43(2):e12717.
    PMID: 31353646 DOI: 10.1111/jfbc.12717
    The present study aimed to outline the physiological and metabolic disparity between chow- and purified ingredient-based high-fat diets and their efficacy in the induction of metabolic syndrome (MetS). Male, 3-week-old Sprague Dawley rats were randomly assigned to chow-based control diet, chow-based high-fat diet, purified control diet, and purified high-fat diet for 12 weeks. Physical and biochemical changes were documented. Chow-based diets, irrespective of the lipid content, resulted in significantly lower weight gain and organ weight compared to purified ingredient-based diets. Circulating insulin, total proteins, albumin, and certain lipid components like the triglycerides, total cholesterol, and high-density lipoprotein-cholesterol were also lower in the chow-based diet groups. Both chow- and purified high-fat diets induced central obesity, hypertension, and hyperglycaemia, but the latter was associated with earlier onset of the metabolic aberrations and additionally, dyslipidaemia. In conclusion, purified high-fat diet is a better diet for MetS induction in rats. PRACTICAL APPLICATIONS: Modeling metabolic syndrome is commonly accomplished with the use of chow- or purified ingredient diets enriched with carbohydrates and/or lipids, but the differences and associated drawbacks are unclear. This study highlights that chow- or modified chow-based diets have a tendency to introduce unwanted metabolic changes which are inconsistent with the progression of metabolic syndrome. Thus, the use of these diets in metabolic disease study should be avoided. On the other hand, purified high-fat diet which can effectively induce the features of metabolic syndrome is highly recommended.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  11. Leptin enhances N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced tumour growth in gastric mucosa of male Sprague-Dawley rats
    Isyraqiah F, Kutty MK, Durairajanayagam D, Singh HJ
    Mol Biol Rep, 2019 Dec;46(6):5967-5975.
    PMID: 31444698 DOI: 10.1007/s11033-019-05030-z
    Individuals who are obese are at a greater risk of developing gastric cancer. They are however also hyperleptinaemic. Chronic leptin treatment has been shown to upregulate numerous cancer-causing genes in the stomach of male Sprague-Dawley rats. It is however unclear if leptin enhances the effect of gastric carcinogens in vivo. This study was therefore done to investigate the effect of leptin on gastric carcinogenesis in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Twenty-four, 6-week old male Sprague-Dawley rats were divided equally into three groups: G1 served as age-matched controls; G2 was treated with MNNG in drinking water ad libitum (200 mg L-1); G3 was given leptin and MNNG. Rats were euthanized after 40 weeks of treatment and their stomachs were removed for histopathology, microarray, and RT-qPCR analysis. Fisher's exact test and one-way ANOVA were used to analyse the data. Fifty percent of the MNNG-treated rats developed gastric hyperplasia (p 
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  12. Fulltext The differential roles of caspase family members in mediating PF4-induced breast cancer apoptosis
    Tengku Din TADAA, Abdul Jalal MI, Seeni A, Shamsuddin S, Jaafar H
    Malays J Pathol, 2018 Dec;40(3):303-312.
    PMID: 30580361
    INTRODUCTION: This study focused on PF4 effects on caspase-3,-6, -7, -8 and -9 which regulate the apopotosis process in breast cancer.

    MATERIALS AND METHODS: Breast tumours were induced in forty 21-day-old female Sprague Dawley rats (SDRs) using MNU until tumour size reached 14.5 mm (SD: 0.5 mm). The rats were then divided into two groups: Group 1 (control injected with 0.9% saline; n = 20), and Group 2 (platelet factor 4 (PF4); n = 20). PF4 was administered through focal intralesional injection at 20 μg/lesion dose. Following 5-day treatment, the SDRs were sacrificed. Subsequently, representative sections from the tumour were obtained for haematoxylin and eosin (H&E) staining. The expressions of caspase-3, -6, -7, -8 and -9 were evaluated using immunohistochemistry (IHC) staining.

    RESULTS: The majority of breast tumour specimens were of aggressive types [ncontrol = 13 (65%); nPF4 = 12 (60%)]. Invasive ductal carcinoma not otherwise specified (IDC-NOS) was the most commonly observed breast tumour histology for control and PF4 groups (n = 8 (40%) in respective groups). PF4-treated group exhibited significant differences in the caspase-3, -6 and -8 expression levels compared to the control group (all p < 0.001). There were no significant differences in caspase-7 (p = 0.347) and caspase-9 (p = 0.373) expression levels between both groups.

    CONCLUSION: This study found that PF4 acts via the caspase-mediated extrinsic apoptosis pathway without the involvement of the intrinsic pathway.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  13. Fulltext Polymeric Microsphere Formulation for Colon Targeted Delivery of 5-Fluorouracil Using Biocompatible Natural Gum Katira
    Karan S, Choudhury H, Chakra BK, Chatterjee TK
    Asian Pac J Cancer Prev, 2019 07 01;20(7):2181-2194.
    PMID: 31350983 DOI: 10.31557/APJCP.2019.20.7.2181
    Controlled release delivery system of chemotherapeutic agents at the site of colon endorses modern drug-entrapped
    delivery tools, which release the entrappedagents at a controlled rate for anextended period providing patient compliance
    and additional protection from the degradinggastric environment. Thus, the present study was aimed to develop
    and optimize a novel polymeric microsphere of 5-fluorouracil (5-FU) using natural gum katira to obtain an optimal
    therapeutic response at the colon. Due course of experimentation, in-vivo safety profile of the gum katira in an animal
    model was established. Modified solvent extraction/evaporation technique wasemployed to encapsulate 5-FU in the
    natural polymeric microsphere and was characterized using in-vitro studies to investigate particle size, morphology,
    encapsulation efficiency and release of the drug from developed formulation. Formulated and optimized polymeric
    microsphere of 5-FU using gum katira polymer own optimal physicochemical characteristics with a fine spherical particle
    with size ranged from 210.37±7.50 to 314.45±7.80 μm.Targeted microsphere exhibited good cytotoxicity and also has
    high drug entrapment efficiency, and satisfactory release pattern of the drug within a time frame of 12 h. Finally, we
    foresee that the optimized polymeric gum katiramicrosphere of 5-FU could be a promising micro-carrier for efficient
    colon drug targeting delivery tool with improved chemotherapeutic efficacy against colon cancer.
    Matched MeSH terms: Rats, Wistar; Rats
  14. Determining weight-bearing tissue condition using peak reactive hyperemia response trend and ultrasonographic features: Implications for pressure ulcer prevention
    Yapp JH, Raja Ahmad RMK, Mahmud R, Mohtarrudin N, Mohamad Yusof L, Abdul Rahim E, et al.
    Wound Repair Regen, 2019 05;27(3):225-234.
    PMID: 30667138 DOI: 10.1111/wrr.12698
    Frequent repositioning is important to prevent pressure ulcer (PU) development, by relieving pressure and recovering damages on skin areas induced by repetitive loading. Although repositioning is the gold standard to prevent PU, there is currently no strategy for determining tissue condition under preventive approaches. In this study, the peak reactive hyperemia (RH) trends and ultrasonographic (US) features are compared with the tissue condition under histopathological examination to determine the potential use of these features in determining the tissue condition noninvasively. Twenty-one male Sprague-Dawley rats (seven per group), with body weight of 385-485 g, were categorized into three groups and subjected to different recovery times, each with three repetitive loading cycles at skin tissues above of right trochanter area. The first, second, and third groups were subjected to short (3 minutes), moderate (10 minutes), and prolonged (40 minutes) recovery, respectively, while applying fixed loading time and pressure (10 minutes and 50 mmHg, respectively), to provide different degree of recovery and tissue conditions (tissue damage and tissue recovery). Peak RH was measured in the three cycles to determine RH trend (increasing, decreasing, and inconsistent). All rat tissues were evaluated using ultrasound at pre- and post-experiment and rated by two raters to categorize the severity of tissue changes (no, mild, moderate, and severe). The tissue condition was also evaluated using histopathological examination to distinguish between normal and abnormal tissues. Most of the samples with increasing RH trend is related to abnormal tissue (71%); while inconsistent RH trends is more related to normal tissue (82%). There is no relationship between the tissue conditions evaluated under ultrasonographic and histopathological examination. Peak RH trend over repetitive loading may serve as a new feature for determining the tissue condition that leading to pressure ulcer.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  15. Fulltext Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats
    Sucedaram Y, Johns EJ, Husain R, Abdul Sattar M, H Abdulla M, Nelli G, et al.
    J Inflamm Res, 2021;14:689-710.
    PMID: 33716510 DOI: 10.2147/JIR.S299083
    Purpose: We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver.

    Methods: Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies.

    Results: HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD.

    Conclusion: Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.

    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  16. Fulltext Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry
    Alkhateeb Y, Jarrar QB, Abas F, Rukayadi Y, Tham CL, Hay YK, et al.
    Molecules, 2020 Jul 06;25(13).
    PMID: 32640512 DOI: 10.3390/molecules25133069
    2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5-80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0-24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0-24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  17. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: a mechanistic study
    Arya A, Al-Obaidi MM, Shahid N, Bin Noordin MI, Looi CY, Wong WF, et al.
    Food Chem Toxicol, 2014 Sep;71:183-96.
    PMID: 24953551 DOI: 10.1016/j.fct.2014.06.010
    The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  18. Total isoflavones from soybean and tempeh reversed scopolamine-induced amnesia, improved cholinergic activities and reduced neuroinflammation in brain
    Ahmad A, Ramasamy K, Jaafar SM, Majeed AB, Mani V
    Food Chem Toxicol, 2014 Mar;65:120-8.
    PMID: 24373829 DOI: 10.1016/j.fct.2013.12.025
    The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1β and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  19. Analysis of urinary andrographolides and antioxidant status after oral administration of Andrographis paniculata leaf extract in rats
    Akowuah GA, Zhari I, Mariam A
    Food Chem Toxicol, 2008 Dec;46(12):3616-20.
    PMID: 18824206 DOI: 10.1016/j.fct.2008.09.008
    A simple high-performance liquid chromatography (HPLC) method was developed to determine the content of andrographolide (AP) and 14-deoxy-11,12-dideoxyandrographolide (DIAP) in a pooled urine of rat obtained within 24h after an oral dose of Andrographis paniculata leaf extract at 1g/kg body weight. Cumulative urinary excretion of AP and DIAP in 24h after oral administration of the extract was 0.88% and 1.61% of oral dose administered, respectively. The extract showed significant reduction (p<0.05) of MDA levels and elevation of total antioxidant status in rat urine samples collected in 24 after oral administration.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
  20. Toxicology study of vanillin on rats via oral and intra-peritoneal administration
    Ho K, Yazan LS, Ismail N, Ismail M
    Food Chem Toxicol, 2011 Jan;49(1):25-30.
    PMID: 20807560 DOI: 10.1016/j.fct.2010.08.023
    Vanillin is useful as anti-sickle cell anemia, anti-mutagen and anti-bacteria agent. However, vanillin must be administered at high concentration and cannot be oxidized by the upper gastrointestinal track of patients to be medically effective. In this study, we assessed the toxic effect of vanillin when administered in an un-oxidized form at high concentrations (150 and 300 mg/kg) via oral and intra-peritoneal injection. It was found that 300 mg/kg vanillin injection caused the rats to be unconscious without exerting any toxic effect on blood cells, kidney and liver. Besides, it showed blood protective property. Further analysis with GenomeLab GeXP genetic system on brain tissues showed that the expression of most xenobiotic metabolism, cell progression, tumor suppressor, DNA damage and inflammation genes were maintained at normal level. However, the expression of a few xenobiotic metabolism, cell cycle arrest and apoptosis genes were up-regulated by 5% ethanol injection. Nevertheless, when 5% ethanol was injected with the presence of vanillin, the expression was back to normal level. It is postulated that vanillin might have neuro-protective property. In conclusion, vanillin is not toxic at high concentration in both oral and intra-peritoneal injection and could provide blood and brain protective properties.
    Matched MeSH terms: Rats, Sprague-Dawley; Rats
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