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Effects of Labisia pumila var alata extracts on the lipid profile, serum antioxidant status and abdominal aorta of high-cholesterol diet rats

Dianita R, Jantan I, Jalil J, Amran AZ

Phytomedicine, 2016 Jul 15;23(8):810-7.
PMID: 27288916 DOI: 10.1016/j.phymed.2016.04.004

BACKGROUND: Previous studies on Labisia pumila var. alata (LPva) have showed that it could inhibit low-density lipoprotein (LDL) oxidation and provide protection on myocardial infarction in rats.
HYPOTHESIS/PURPOSE: We hypothesized that LPva extracts can modulate the lipid profiles and serum antioxidant status of hypercholesterolemic rats. In the present study, we investigated the effects of aqueous and 80% ethanol extracts of LPva on atherogenic and serum antioxidant parameters as well as changes in abdominal aorta of high-cholesterol diet rats.
METHODS: The major components of the extracts, gallic acid, flavonoids and alkyl resorcinols were analyzed by using a validated reversed phase HPLC method. The rats were induced to hypercholesterolemic status with daily intake of 2% cholesterol for a duration of 8 weeks. Three different doses (100, 200 and 400mg/kg) of the extracts were administered daily on the 4th week onwards. The rats were then sacrificed and the blood was collected via abdominal aorta and serum was separated by centrifugation for biochemical analysis. Part of the aorta tissues were excised immediately for histopathological examination.
RESULTS: The serum of LPva treated rats showed significant reduction in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels and the abdominal aorta showed a significant decrease of atheroma lesions in treated rats. Serum lipid profiles of treated rats showed a decrease in total cholesterol, total triglycerides and low-density lipoprotein (LDL) levels as compared to control group. The atherogenic indices in treated rats were significantly improved along with an increasing level of serum high-density lipoprotein (HDL). The extracts also exhibited significant increase of antioxidant enzymes and decrease of MDA as a product of lipid peroxidation.
CONCLUSION: LPva extracts can reduce the risk of dyslipidemia by improving the serum lipid profiles and modulating serum antioxidants.

Matched MeSH terms: Rats, Wistar
Fulltext Cystathione gamma lyase/Hydrogen Sulphide Pathway Up Regulation Enhances the Responsiveness of α1A and α1B-Adrenoreceptors in the Kidney of Rats with Left Ventricular Hypertrophy

Ahmad A, Sattar MA, Azam M, Abdulla MH, Khan SA, Hashmi F, et al.

PLoS One, 2016;11(5):e0154995.
PMID: 27191852 DOI: 10.1371/journal.pone.0154995

The purpose of the present study was to investigate the interaction between H2S and NO (nitric oxide) in the kidney and to evaluate its impact on the functional contribution of α1A and α1B-adrenoreceptors subtypes mediating the renal vasoconstriction in the kidney of rats with left ventricular hypertrophy (LVH). In rats the LVH induction was by isoprenaline administration and caffeine in the drinking water together with intraperitoneal administration of H2S. The responsiveness of α1A and α1B to exogenous noradrenaline, phenylephrine and methoxaminein the absence and presence of 5-methylurapidil (5-MeU) and chloroethylclonidine (CEC) was studied. Cystathione gamma lyase (CSE), cystathione β synthase (CBS), 3-mercaptopyruvate sulphar transferase (3-MST) and endothelial nitric oxide synthase (eNOS) were quantified. There was significant up regulation of CSE and eNOS in the LVH-H2S compared to the LVH group (P<0.05). Baseline renal cortical blood perfusion (RCBP) was increased (P<0.05) in the LVH-H2S compared to the LVH group. The responsiveness of α1A-adrenergic receptors to adrenergic agonists was increased (P<0.05) after administration of low dose 5-Methylurapidil in the LVH-H2S group while α1B-adrenergic receptors responsiveness to adrenergic agonists were increased (P<0.05) by both low and high dose chloroethylclonidine in the LVH-H2S group. Treatment of LVH with H2S resulted in up-regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways in the kidney. These up regulation of CSE/H2S, CBS, and 3-MST and eNOS/NO/cGMP pathways enhanced the responsiveness of α1A and α1B-adrenoreceptors subtypes to adrenergic agonists in LVH-H2S. These findings indicate an important role for H2S in modulating deranged signalling in the renal vasculature resulting from LVH development.

Matched MeSH terms: Rats, Wistar
Protective effect of diallylsulphide against mercuric chloride-induced hepatic injury in rats

Ansar S, Iqbal M

Hum Exp Toxicol, 2016 Dec;35(12):1305-1311.
PMID: 26825963

The present study was undertaken to evaluate the effect of diallylsulphide (DAS) against mercuric chloride (HgCl2)-induced oxidative stress in rat livers. Rats were randomly divided into four groups of six rats each and exposed to HgCl2 (50 mg/kg/body weight (b.w.)) intraperitoneally and/or DAS (200 mg/kg/b.w.) by gavage. HgCl2 administration enhanced alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels (p < 0.05) with reduction in the levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). However, treatment with DAS markedly attenuated HgCl2-induced biochemical alterations in liver and serum transaminases (AST and ALT; p < 0.05). Further, biochemical results were confirmed by histopathological changes as compared to HgCl2-intoxicated rats. Histopathology of liver also showed that administration of DAS significantly reduced the damage generated by HgCl2 The present study suggests that DAS shows antioxidant activity and plays a protective role against mercury-induced oxidative damage in the rat livers.

Matched MeSH terms: Rats, Wistar
Fulltext Nanotoxic profiling of novel iron oxide nanoparticles functionalized with perchloric acid and SiPEG as a radiographic contrast medium

Mohamed MI, Mohammad MK, Abdul Razak HR, Abdul Razak K, Saad WM

Biomed Res Int, 2015;2015:183525.
PMID: 26075217 DOI: 10.1155/2015/183525

Emerging syntheses and findings of new metallic nanoparticles (MNPs) have become an important aspect in various fields including diagnostic imaging. To date, iodine has been utilized as a radiographic contrast medium. However, the raise concern of iodine threats on iodine-intolerance patient has led to search of new contrast media with lower toxic level. In this animal modeling study, 14 nm iron oxide nanoparticles (IONPs) with silane-polyethylene glycol (SiPEG) and perchloric acid have been assessed for toxicity level as compared to conventional iodine. The nanotoxicity of IONPs was evaluated in liver biochemistry, reactive oxygen species production (ROS), lipid peroxidation mechanism, and ultrastructural evaluation using transmission electron microscope (TEM). The hematological analysis and liver function test (LFT) revealed that most of the liver enzymes were significantly higher in iodine-administered group as compared to those in normal and IONPs groups (P < 0.05). ROS production assay and lipid peroxidation indicator, malondialdehyde (MDA), also showed significant reductions in comparison with iodine group (P < 0.05). TEM evaluation yielded the aberration of nucleus structure of iodine-administered group as compared to those in control and IONPs groups. This study has demonstrated the less toxic properties of IONPs and it may postulate that IONPs are safe to be applied as radiographic contrast medium.

Matched MeSH terms: Rats, Wistar
Fulltext The use of Piper sarmentosum leaves aqueous extract (Kadukmy™) as antihypertensive agent in spontaneous hypertensive rats

Mohd Zainudin M, Zakaria Z, Megat Mohd Nordin NA

BMC Complement Altern Med, 2015 Mar 10;15:54.
PMID: 25887182 DOI: 10.1186/s12906-015-0565-z

BACKGROUND: The National Health and Morbidity Survey in 2011 estimated that 35.1% (5.7 million) of Malaysian adults aged 18 and older suffer from hypertension. Hypertension is still treated by conventional medicine despite its exact aetiology being unknown. Studies showed that oxidative stress and low availability of nitric oxide (NO) causes an increase in vascular wall tension and increase blood pressure. Piper sarmentosum (PS) a traditional Malay herbal plant is well known for its high antioxidant content. Antioxidant is useful in improving cardiovascular diseases particularly hypertension. Thus, it is beneficial to determine the effect of PS leaves aqueous extract (Kadukmy™) on the blood pressure, NO level, oxidative stress markers and serum cholesterol level of the Spontaneous Hypertensive Rats (SHR).
METHODS: Rats were devided into five groups consisting of three treatment groups and two control groups. Baseline blood investigations were done before and following commencement of treatment. Spontaneous hypertensive rats were treated for 28 consecutive days and the blood pressure was measured weekly.
RESULTS: Kadukmy™ administration showed a significant reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) (P

Matched MeSH terms: Rats, Wistar
Inhibitory effect of phenethyl isothiocyanate against benzo[a] pyrene-induced rise in CYP1A1 mRNA and apoprotein levels as its chemopreventive properties

Abdull Razis AF, Konsue N, Ioannides C

Asian Pac J Cancer Prev, 2015;16(7):2679-83.
PMID: 25854346

BACKGROUND: Phenethyl isothiocyanate (PEITC), the most comprehensively studied aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly through modulation of biotransformation enzymes responsible for metabolizing carcinogens in the human body. Humans are often exposed to carcinogenic factors, some of which through the diet, such as polycyclic aromatic hydrocarbon benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy.
OBJECTIVE: To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels.
MATERIALS AND METHODS: Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and 5 μM in the presence of PEITC (1-25 μM) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting.
RESULTS: Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A.
CONCLUSIONS: It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential.

Matched MeSH terms: Rats, Wistar
Fulltext 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease

Xu J, Jiang H, Li J, Cheng KK, Dong J, Chen Z

PLoS One, 2015;10(4):e0119654.
PMID: 25849323 DOI: 10.1371/journal.pone.0119654

Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.

Matched MeSH terms: Rats, Wistar
Histamine induced decrease of lecithin levels in broncho-alveolar lavage fluid of rats is mediated by H2 receptor

Rao GJ

Asian Pac J Allergy Immunol, 2000 Sep;18(3):169-71.
PMID: 11270474

Lecithin, a major surface active substance of the surfactant system of the lung, was estimated in broncho-alveolar lavage (BAL) fluid in four groups of healthy adult male albino rats. Rats from group I were not administered any drug and acted as controls. Group II were administered histamine diphosphate. Group III were given H1 blocker (pyrilamine maleate) followed by histamine diphosphate. Group IV received H2 blocker (ranitidine hydrochloride) followed by histamine diphosphate. Lecithin content of BAL fluid in the control group was compared with that in the other three groups. A significant decrease in lecithin content was observed in the rats that received either histamine diphosphate or H1 blocker followed by histamine diphosphate. However, compared to control rats no significant difference in lecithin content was seen in rats that received H2 blocker followed by histamine diphosphate. The results clearly indicate that the decrease in surface active lecithin content in BAL fluid following administration of histamine diphosphate was unaffected by prior administration of H1 blocker, but was blocked by prior administration of H2 blocker. It was concluded that histamine induced decrease in lecithin content of BAL fluid is mediated through H2 receptors. Since the predominant source of intra-alveolar lecithin are Type II cells of the alveolar epithelium, It is possible that Type II cells have H2 receptors, stimulation of which resulted in decreased intraalveolar lecithin.

Matched MeSH terms: Rats, Wistar
Polyphenol-enriched extract of oil palm fronds (Elaeis guineensis) promotes vascular relaxation via endothelium-dependent mechanisms

Abeywardena M, Runnie I, Nizar M, Suhaila M, Head R, Suhaila Momamed

Asia Pac J Clin Nutr, 2002;11 Suppl 7:S467-72.
PMID: 12492636

Plant-based polyphenolic compounds have been reported to possess cardiovascular health benefits. Several dietary sources, including herbs and spices, fruits and vegetables, and tea and wine, contain an array of biologically active compounds that have been shown to be effective in retarding oxidation of low-density lipoproteins (LDL) and promoting vascular relaxation. In the present study four different plant sources, both edible and non-edible, were evaluated for potential activity. Organic extracts enriched in polyphenols were prepared from palm fronds (Elaesis guineensis); lemongrass (Cymbopogon citrates); papaya shoots (Carica papaya) and green chilli (Capsicum frutescenes) and tested for their ability to prevent in vitro oxidation of LDL, and for potential vascular relaxation actions. Rings of rat thoracic aorta and isolated perfused mesenteric vascular beds were mounted in organ baths, contracted using a half-maximal dose of noradrenaline and exposed to cumulative additions of test extracts. Palm frond extract resulted in considerable relaxation (>75%) in both preparations and was found to be endothelium-dependent as removal of endothelium or inhibition of endogenous nitric oxide (NO) led to a total loss in relaxant activity. Lemongrass extract caused a greater relaxation action in the mesenteric preparation compared to aortic rings, and appears to be mediated via NO-independent and non-prostanoid mechanisms. Of the extracts tested, palm fronds also demonstrated the highest antioxidant capacity, as determined by the ferric reducing activity/potential assay, and resulted in a significant delay (P < 0.05) in the oxidation of LDL. Collectively, these preliminary findings lend further support to the potential cardiovascular actions of plant polyphenols and also identify oil palm fronds as containing constituents that promote vascular relaxation via endothelium-dependent mechanisms.

Matched MeSH terms: Rats, Wistar
Cyproterone acetate and reversal of the impaired endometrial decidualization in streptozotocin-diabetic pseudopregnant rats

Zakaria R, Ismail Z, Chatterjee A

Pharmacol Res, 2000 Aug;42(2):183-6.
PMID: 10887050

Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when the uterus was sensitized by a sequence of oestrogen and progesterone. In this study, we examined whether the impaired expression of endometrial decidualization in the pseudopregnant rat is linked with diabetes-associated hypersecretion of testosterone. Rats were made pseudopregnant by sterile mating. Diabetes was induced by streptozotocin on day 1 p.c. Deciduogenic stimulus was given on day 5 p.c. Treatment of cyproterone acetate (10 mg kg(-1)) was scheduled from day 5 through day 9 p.c. Animals were killed on day 10 p.c, and the degree of endometrial decidual growth, plasma levels of oestradiol, progesterone, ACTH and testosterone were determined. Results showed that compared to controls there was a concomitant drop in endometrial decidual growth concurrently with impaired levels of oestradiol and progesterone in diabetic pseudopregnant rats. ACTH and testosterone levels were, however, profoundly elevated. Cyproterone acetate treatment in the diabetic pseudopregnant rat resulted in a simultaneous elevation of oestradiol and progesterone, which eventually helped the endometrial differentiation to decidua in the diabetic pseudopregnant rat parallel to controls. Present experimental data suggest that diabetes-associated impaired endometrial decidualization in the pseudopregnant rat is possibly caused by testosterone-induced oestrogen deficiency.

Matched MeSH terms: Rats, Wistar
Differential effect of adrenocorticosteroids on 11 beta-hydroxysteroid dehydrogenase bioactivity at the anterior pituitary and hypothalamus in rats

Idrus RB, Mohamad NB, Morat PB, Saim A, Abdul Kadir KB

Steroids, 1996 Aug;61(8):448-52.
PMID: 8870163

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been identified in a wide variety of tissues. The differential distribution of 11 beta-OHSD suggests that this enzyme has locally defined functions that vary from region to region. The aim of this study was to investigate the effects of the glucocorticoids B and dexamethasone (DM), the mineralocorticoid deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All treatments were in vivo except GE, which was used in vitro. At the end of treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity, expressed as the percentage conversion of B to A in the presence of NADP, 11 beta-OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the HT. Adrenalectomy significantly increased the enzyme activity in the AP (P < 0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P < 0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity significantly. We conclude that the modulation of 11 beta-OHSD is both steroid specific and tissue specific.

Matched MeSH terms: Rats, Wistar
Fulltext Increased exposure to sodium during pregnancy and lactation changes basal and induced behavioral and neuroendocrine responses in adult male offspring

Silva MS, Lúcio-Oliveira F, Mecawi AS, Almeida LF, Ruginsk SG, Greenwood MP, et al.

Physiol Rep, 2017 Mar;5(6).
PMID: 28336818 DOI: 10.14814/phy2.13210

Excessive sodium (Na+) intake in modern society has been associated with several chronic disorders such as hypertension. Several studies suggest that early life events can program physiological systems and lead to functional changes in adulthood. Therefore, we investigated behavioral and neuroendocrine responses under basal conditions and after 48 h of water deprivation in adult (60-day-old Wistar rats) male, Wistar rats originating from dams were offered only water or 0.15 mol/L NaCl during pregnancy and lactation. Early life salt exposure induced kidney damage, as shown by a higher number of ED-1 positive cells (macrophages/monocytes), increased daily urinary volume and Na+ excretion, blunted basal water intake and plasma oxytocin levels, and increased plasma corticosterone secretion. When challenged with water deprivation, animals exposed to 0.15 mol/L NaCl during early life showed impaired water intake, reduced salt preference ratio, and vasopressin (AVP) secretion. In summary, our data demonstrate that the perinatal exposure to excessive Na+ intake can induce kidney injury in adult offspring and significantly affect the key mechanisms regulating water balance, fluid intake, and AVP release in response to water deprivation. Collectively, these novel results highlight the impact of perinatal programming on the homeostatic mechanisms regulating fluid and electrolyte balance during exposure to an environmental stress (i.e. dehydration) in later life.

Matched MeSH terms: Rats, Wistar
Tocotrienol offers better protection than tocopherol from free radical-induced damage of rat bone

Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S

Clin Exp Pharmacol Physiol, 2005 Sep;32(9):761-70.
PMID: 16173934

1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.

Matched MeSH terms: Rats, Wistar
Design, synthesis, in vitro evaluation, molecular docking and ADME properties studies of hybrid bis-coumarin with thiadiazole as a new inhibitor of Urease

Alomari M, Taha M, Imran S, Jamil W, Selvaraj M, Uddin N, et al.

Bioorg Chem, 2019 11;92:103235.
PMID: 31494327 DOI: 10.1016/j.bioorg.2019.103235

Hybrid bis-coumarin derivatives 1-18 were synthesized and evaluated for their in vitro urease inhibitory potential. All compounds showed outstanding urease inhibitory potential with IC50 value (The half maximal inhibitory concentration) ranging in between 0.12 SD 0.01 and 38.04 SD 0.63 µM (SD standard deviation). When compared with the standard thiourea (IC50 = 21.40 ± 0.21 µM). Among these derivatives, compounds 7 (IC50 = 0.29 ± 0.01), 9 (IC50 = 2.4 ± 0.05), 10 (IC50 = 2.25 ± 0.05) and 16 (IC50 = 0.12 ± 0.01) are better inhibitors of the urease compared with thiourea (IC50 = 21.40 ± 0.21 µM). To find structure-activity relationship molecular docking as well as absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Various spectroscopic techniques like 1H NMR, 13C NMR, and EI-MS were used for characterization of all synthesized analogs. All compounds were tested for cytotoxicity and found non-toxic.

Matched MeSH terms: Rats, Wistar
Sperm parameters quality and reproductive effects of methanolic extract of Alchornea cordifolia leaves on senescent male rats

Ngaha Njila MI, Massoma Lembè D, Koloko BL, Yong Meng G, Ebrahimi M, Awad EA, et al.

Andrologia, 2019 Oct;51(9):e13359.
PMID: 31353623 DOI: 10.1111/and.13359

The effect of the methanolic extract of Alchornea cordifolia leaves on the fertility of senescent male rats was assessed in this study. 40 rats received daily distilled water, testosterone, 200 and 400 mg/kg of extract of Alchornea cordifolia. The reproductive organs weight, the gonadotropins, testosterone and cholesterol level, the sperm parameters, histology of the testes and epididymis were assessed. The weight of testes and prostate (400 mg/kg) significantly increased (p

Matched MeSH terms: Rats, Wistar
PKC inhibitor reversed the suppressive effect of orexin-A on IPSCs of locus coeruleus neurons in naloxone-induced morphine withdrawal

Davoudi M, Vijeepallam K, Azizi H, Mirnajafi-Zadeh J, Semnanian S

J Neural Transm (Vienna), 2019 11;126(11):1425-1435.
PMID: 31493096 DOI: 10.1007/s00702-019-02064-2

The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14-P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.

Matched MeSH terms: Rats, Wistar
Guggulsterone, a farnesoid X receptor antagonist lowers plasma trimethylamine-N-oxide levels: An evidence from in vitro and in vivo studies

Gautam A, Paudel YN, Abidin S, Bhandari U

Hum Exp Toxicol, 2019 Mar;38(3):356-370.
PMID: 30526076 DOI: 10.1177/0960327118817862

The current study investigated the role of guggulsterone (GS), a farnesoid X receptor antagonist, in the choline metabolism and its trimethylamine (TMA)/flavin monooxygenases/trimethylamine-N-oxide (TMAO) inhibiting potential in a series of in vitro and in vivo studies as determined by high-performance liquid chromatography (HPLC), mass spectroscopy (MS), and liquid chromatography (LC)-MS techniques. Atherosclerosis (AS) was successfully induced in a group of experimental animals fed with 2% choline diet for 6 weeks. Serum lipid profiles such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured. Pro-inflammatory cytokines levels, markers for a hepatic injury, and oxidative stress markers were assessed. Interestingly, GS reduced the level of TMA/TMAO in both in vitro and in vivo studies as demonstrated by the peaks obtained from HPLC, MS, and LC-MS. Furthermore, GS exhibited cardioprotective and antihyperlipidemic effects as evidenced by the attenuation of levels of several serum lipid profiles and different atherogenic risk predictor indexes. GS also prevented hepatic injury by successfully restoring the levels of hepatic injury biomarkers to normal. Similarly, GS inhibited the production of pro-inflammatory cytokines levels, as well as GS, enhanced antioxidant capacity, and reduced lipid peroxidation. Histopathological study of aortic sections demonstrated that GS maintained the normal architecture in AS-induced rats. On the basis of results obtained from current investigation, we suggest that GS might have a great therapeutic potential for the treatment of AS.

Matched MeSH terms: Rats, Wistar
Fulltext Protective effect of Centella asiatica against D-galactose and aluminium chloride induced rats: Behavioral and ultrastructural approaches

Chiroma SM, Hidayat Baharuldin MT, Mat Taib CN, Amom Z, Jagadeesan S, Adenan MI, et al.

Biomed Pharmacother, 2019 Jan;109:853-864.
PMID: 30551539 DOI: 10.1016/j.biopha.2018.10.111

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the commonest cause of dementia among the aged people. D-galactose (D-gal) is a senescence agent, while aluminium is a known neurotoxin linked to pathogenesis of AD. The combined administration of rats with d-gal and aluminium chloride (AlCl3) is considered to be an easy and a cheap method to obtain an animal model of AD. The plant Centella asiatica (CA) is reported to exert neuroprotective effects both in vitro and in vivo. Therefore, this study explored the protective effects of CA on cognition and brain ultrastructure in d-gal and AlCl3 induced rats.
MATERIALS AND METHODS: Rats were exposed to d-gal 60 mg/kg/b.wt/day + AlCl3 200 mg/kg/b.wt/day and CA (200, 400 and 800 mg/kg/b.wt/day) and 1 mg/kg/b.wt/day of donepezil for 70 days. Different cognitive paradigms viz. T maze spontaneous alternation, modified elevated plus maze and novel object recognition test, were used to evaluate full lesions of the hippocampus, spatial learning and memory and non-spatial learning and memory respectively. Nissl's staining was used to determine the survival of hippocampus CA1 pyramidal cells, while transmission electron microscopy was used to check the ultrastructural changes.
RESULTS: The results revealed that d-gal and AlCl3 could significantly impair behavior and cognitive functions, besides causing damage to the hippocampal CA1 pyramidal neurons in rats. In addition, it also caused ultrastructural morphological alterations in rat hippocampus. Conversely, co-administration o;f CA, irrespective of the dosage used, alleviated the cognitive impairments and pathological changes in the rats comparable to donepezil.
CONCLUSION: In conclusion the results suggest that CA could protect cognitive impairments and morphological alterations caused by d-gal and AlCl3 toxicity in rats. Biochemical and molecular studies are ongoing to elucidate the probable pharmacodynamics of CA.

Matched MeSH terms: Rats, Wistar
Quercetin exerts preventive, ameliorative and prophylactic effects on cadmium chloride - induced oxidative stress in the uterus and ovaries of female Wistar rats

Nna VU, Usman UZ, Ofutet EO, Owu DU

Food Chem Toxicol, 2017 Apr;102:143-155.
PMID: 28229914 DOI: 10.1016/j.fct.2017.02.010

This study examined the possible protective effect of quercetin(QE) on cadmium chloride (CdCl2) - induced reproductive toxicity in female rats. Cadmium (Cd) accumulated in the uterus and ovaries of rats, decreased antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and raised the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the uterus and ovaries of rats. Serum concentrations of estradiol, progesterone, follicle stimulating hormone and luteinizing hormone decreased significantly after CdCl2 administration. Caspase-3 activity significantly increased in the ovaries, with an increase in Bax and a decrease in Bcl-2 protein expressions after CdCl2 treatment. Histopathology of the ovaries revealed significant decrease in follicle number, while the uterus showed cyst-like endometrial glands. All three models of QE treatment [pre-treatment (QE + CdCl2), post-treatment (CdCl2+QE), simultaneous treatment (CdCl2/QE)] decreased Cd accumulation, MDA, H2O2, and increased SOD, CAT and GPx activities in the uterus and ovaries, decreased apoptosis of follicular cells, and increased serum reproductive hormones. However, the QE pre-treated model offered better protection against CdCl2 relative to the other two models. These results suggest that, QE exerts multi-mechanistic protective effects against cadmium toxicity attributable to its antioxidant and anti-apoptotic actions.

Matched MeSH terms: Rats, Wistar
S-allylcysteine improves ischemia/reperfusion alteration on cardiac function, antioxidant, and mitochondrial permeability

Aziz NF, Ramalingam A, Latip J, Zainalabidin S

Life Sci, 2021 Mar 15;269:119080.
PMID: 33465387 DOI: 10.1016/j.lfs.2021.119080

S-Allylcysteine (SAC) is an extensively studied natural product which has been proven to confer cardioprotection. This potentiates SAC into many clinical relevance possibilities, hence, the use of it ought to be optimally elucidated. To further confirm this, an ischemia/reperfusion model has been used to determine SAC at 10 mM and 50 mM on cardiac function, cardiac marker, and mitochondrial permeability. Using Langendorff setup, 24 adult male Wistar rats' hearts were isolated to be perfused with Kreb-Henseleit buffer throughout the ischemia/reperfusion method. After 20 min of stabilization, global ischemia was induced by turning off the perfusion for 35 min followed by 60 min of reperfusion with either Kreb-Henseleit buffer or SAC with the dose of 10 mM or 50 mM. The cardiac function was assessed and coronary effluent was collected at different timepoints throughout the experiment for lactate dehydrogenase (LDH) measurement. The harvested hearts were then used to measure glutathione while isolated mitochondria for mPTP analysis. SAC-reperfused hearts were shown to prevent the aggravation of cardiac function after I/R induction. It also dose-dependently upregulated glutathione reductase and glutathione level and these were also accompanied by significant reduction of LDH leakage and preserved mitochondrial permeability. Altogether, SAC dose-dependently was able to recover the post-ischemic cardiac function deterioration alongside with improvement of glutathione metabolism and mitochondrial preservation. These findings highly suggest that SAC when sufficiently supplied to the heart would be able to prevent the deleterious complications after the ischemic insult.

Matched MeSH terms: Rats, Wistar

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