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Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Ameliorates Nonspatial Learning and Memory Deficits in Rats with Hypercholesterolemia and Alzheimer's Disease

Rahman MA, Hossain S, Abdullah N, Aminudin N

Int J Med Mushrooms, 2020;22(11):1067-1078.
PMID: 33426838 DOI: 10.1615/IntJMedMushrooms.2020036354

Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting memory and learning of aged people. Hypercholesterolemia had been implicated as one of the stark hallmarks of AD. Recent AD control guidelines have suggested lifestyle modification to slow down the progression of AD. In this regard, medicinal mushroom Ganoderma lucidum seems apt. In the present study, hot water extract of G. lucidum (200 mg/kg body weight) was fed to the hypercholesterolemic and AD model rats for 8 weeks. Nonspatial memory and learning abilities of the model animals was assessed using novel object recognition (NOR) test, rotarod test, and locomotor/open-field test. Then, the animals were sacrificed and transmission electron micrograph (TEM) view of the hippocampal neurons was assessed. In all the nonspatial memory and learning tests, the G. lucidum HWE fed rats performed better indicating improved memory and learning abilities. TEM view showed regular arrangement of the neurons in the G. lucidum HWE fed rats compared with those of the deranged arrangement of the AD rats. G. lucidum might have aided in restoring the memory and learning abilities of the AD model animals through maintaining neuronal structure and function. Thus, G. lucidum could be suggested as a medicotherapeutic agent against AD.

Matched MeSH terms: Rats, Wistar
Stingless Bee Honey Reduces Anxiety and Improves Memory of the Metabolic Disease-induced Rats

Arshad N', Lin TS, Yahaya MF

CNS Neurol Disord Drug Targets, 2020;19(2):115-126.
PMID: 31957619 DOI: 10.2174/1871527319666200117105133

BACKGROUND: Scientific studies support the evidence of the involvement of Metabolic Syndrome (MetS) in the progression of neurodegenerative diseases through oxidative stress. Consumption of antioxidant compounds was found to be beneficial for brain-health as it reduced the brain oxidative stress level and improved cognitive performance in animals. Stingless bee honey or locally known as Kelulut Honey (KH) has high phenolic content and is widely used as a food supplement.
OBJECTIVES: In this study, we aimed to investigate the effects of KH on the brain of MetS-induced rats.
METHODS: Forty male Wistar rats were divided into 5 groups; 8 weeks (C8) and 16 weeks control groups (C16), groups that received High-Carbohydrate High Fructose (HCHF) diet for 8 weeks (MS8) and 16 weeks (MS16), and a group that received HCHF for 16 weeks with KH supplemented for the last 35 days (KH).
RESULTS: Serum fasting blood glucose decreased in the KH group compared to the MS16 group. HDL levels were significantly decreased in MetS groups compared to control groups. Open field experiments showed that KH group exhibits less anxious behavior compared to the MetS group. Probe trial of Morris water maze demonstrated significant memory retention of KH group compared to the MS16 group. Nissl staining showed a significant decrease in the pyramidal hippocampal cells in the MS16 compared to the KH group.
CONCLUSION: KH has the ability to normalise blood glucose and reduce serum triglyceride and LDL levels in MetS rats, while behavior studies complement its effect on anxiety and memory. This shows a promising role of KH in attenuating neurodegenerative diseases through the antioxidant activity of its polyphenolic content.

Matched MeSH terms: Rats, Wistar
African Walnuts (Tetracarpidium conophorum) Modulate Hepatic Lipid Accumulation in Obesity via Reciprocal Actions on HMG-CoA Reductase and Paraoxonase

Uti DE, Atangwho IJ, Eyong EU, Umoru GU, Egbung GE, Rotimi SO, et al.

Endocr Metab Immune Disord Drug Targets, 2020;20(3):365-379.
PMID: 31339080 DOI: 10.2174/1871530319666190724114729

BACKGROUND: Obesity is characterized by increased body fat and involves an imbalance between the synthesis and degradation of lipids.
OBJECTIVE: The study aimed to investigate the effect of African walnuts (Tetracarpidium conophorum) on lipids storage and the regulatory enzymes of hepatic lipid metabolism in obese rats.
METHODS: Nuts were extracted in ethanol (WE) and further separated to obtain the ethyl-acetate fraction (ET) and the residue (RES). These were administered orally to 3 groups of monosodium glutamate- obese rats (n = 6), respectively, for 6 weeks. Other groups in the study were: normal (NC), obese control (OC) and standard control (SC) which received orlistat. Hepatic total lipids, total phospholipids, triacylglycerol (TG), total cholesterol (TCHOL), 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase and paraoxonase were studied.
RESULTS: Total lipids, TG and TCHOL which increased in OC compared to NC group, decreased. HMG-CoA reductase activity decreased in the 3 study groups relative to OC. Paraoxonase activity which decreased in OC was up-regulated, while the magnitude of hepatic cholesterol decreased from 94.32 % in OC to 52.19, 65.43 and 47.04 % with WE, ET and RES, respectively. Flavonoids, alkaloids, glycosides, tannins and saponins were detected in the nut. GC-MS analysis revealed 16, 18 and 10 volatile components in WE, ET and RES, respectively. Unsaturated fatty acids (linolenic acids: 33.33, 47.95 and 50.93 %, and α-linolenic acids: 25, 19.66 and 26.63 %) in WE, ET and RES, respectively, are the most abundant, and likely to be responsible for the observed activity.
CONCLUSION: African walnuts can prevent hepatic lipid accumulation through reciprocal actions on HMG-CoA reductase and paraoxonase in obesity.

Matched MeSH terms: Rats, Wistar
Fulltext Neuroprotection of Tropical Fruit Juice Mixture via the Reduction of iNOS Expression and CRH Level in β-Amyloid-Induced Rats Model of Alzheimer's Disease

Ooi TC, Ahmad Munawar M, Mohd Rosli NH, Abdul Malek SNA, Rosli H, Ibrahim FW, et al.

Evid Based Complement Alternat Med, 2020;2020:5126457.
PMID: 32382294 DOI: 10.1155/2020/5126457

This study aimed to determine the effects of tropical fruit juice mixture (pomegranate, white guava, and Roselle) on biochemical, behavioral, and histopathological changes of β-amyloid- (Aβ-) induced rats. Formulation 8 (F8) of tropical fruit juice mixture was chosen for this present study due to its high phenolic content and antioxidant capacity. Forty Wistar male rats were divided into five groups: dPBS (sham-operated control), dAβ (Aβ control), JPBS (F8 and PBS), JAβ (F8 and Aβ), and IBFAβ (ibuprofen and Aβ). F8 (5 ml/kg BW), and ibuprofen (10 ml/kg BW) was given orally daily for four weeks before the intracerebroventricular infusion of Aβ for two weeks. Histological analysis and neuronal count of hippocampus tissue in the Cornu Ammonis (CA1) region showed that supplementation with F8 was able to prevent Aβ-induced tissue damage and neuronal shrinkage. However, no significant difference in locomotor activity and novel object recognition (NOR) percentage was detected among different groups at day 7 and day 14 following Aβ infusion. Only effect of time differences (main effect of day) was observed at day 7 as compared to day 14, where reduction in locomotor activity and NOR percentage was observed in all groups, with F (1, 7) = 6.940, p < 0.05 and F (1, 7) = 7.152, p < 0.05, respectively. Besides, the MDA level of the JAβ group was significantly lower (p < 0.01) than that of the dPBS group. However, no significant changes in SOD activity were detected among different groups. Significant reduction in plasma CRH level (p < 0.05) and iNOS expression (p < 0.01) in the brain was detected in the JAβ group as compared to the dAβ group. Hence, our current findings suggest that the tropical fruit juice mixture (F8) has the potential to protect the rats from Aβ-induced neurotoxicity in brain hippocampus tissue possibly via its antioxidant properties and the suppression of iNOS expression and CRH production.

Matched MeSH terms: Rats, Wistar
Fulltext The Beneficial Effects of Stingless Bee Honey from Heterotrigona itama against Metabolic Changes in Rats Fed with High-Carbohydrate and High-Fat Diet

Ramli NZ, Chin KY, Zarkasi KA, Ahmad F

Int J Environ Res Public Health, 2019 12 07;16(24).
PMID: 31817937 DOI: 10.3390/ijerph16244987

Metabolic syndrome (MetS) is a group of conditions including central obesity, hyperglycemia, dyslipidemia, and hypertension that increases the risk for cardiometabolic diseases. Kelulut honey (KH) produced by stingless honey bees has stronger antioxidant properties compared to other honey types and may be a functional food against MetS. This study aimed to determine the efficacy of KH in preventing metabolic changes in rats with MetS induced by high-carbohydrate and high-fat (HCHF) diet. Male Wistar rats were randomly assigned to the control (C), HCHF diet-induced MetS (S), and MetS supplemented with KH (K) groups. The K group was given KH (1 g/kg/day) for eight weeks. Compared to the control, the S group had significant higher omental fat mass, serum triglyceride, systolic blood pressure, diastolic blood pressures, adipocyte area, and adipocyte perimeter (p < 0.05). KH supplementation significantly prevented these MetS-induced changes at week 16 (p < 0.05). Several compounds, including 4-hydroxyphenyl acetic acid, coumaric and caffeic acids, had been detected via liquid chromatography-mass spectrometry analysis that might contribute to the reversal of these changes. The beneficial effects of KH against MetS-induced rats provide the basis for future KH research to investigate its potential use in humans and its molecular mechanisms in alleviating the disease.

Matched MeSH terms: Rats, Wistar
Anti-inflammatory and renal protective effect of gingerol in high-fat diet/streptozotocin-induced diabetic rats via inflammatory mechanism

Song S, Dang M, Kumar M

Inflammopharmacology, 2019 Dec;27(6):1243-1254.
PMID: 30826930 DOI: 10.1007/s10787-019-00569-6

P38 mitogen-activated protein kinase (p38 MAPK), a tissue inflammatory factor can be activated under oxidative stress and in conditions associated with hyperglycemia. Gingerol containing various natural herbs has been extensively studied for its pharmacological actions both in reducing the inflammation and as immunity booster. The aim of the current investigation was to examine the renal protective effect of gingerol in high-fat diet/streptozotocin-induced type II diabetes mellitus in a rat model.NRK 52E cells were divided into normal and high glucose group treated with gingerol. The methylthiazotetrazolium assay was used to establish the cell proliferation progress. Streptozotocin-inducted diabetes in rats was treated with gingerol for 16 weeks. The blood glucose, serum creatinine, body weight, food intake, biochemical, antioxidant and haematological parameters were assayed to establish the correlation. Pro-inflammatory cytokines including Il-1β, IL-6, TNF-α; inflammatory mediator COX-2, PGE2, NF-kB, p38MAPK, and TGF-β, were also determined to assess the molecular mechanism. Gingerol exhibited the protective effect on the high glucose level induced NRK 52E cells and did not show any effect on the normal cells. Gingerol significantly (P

Matched MeSH terms: Rats, Wistar
Fulltext Resveratrol Supplementation Protects Against Nicotine-Induced Kidney Injury

Ramalingam A, Santhanathas T, Shaukat Ali S, Zainalabidin S

Int J Environ Res Public Health, 2019 11 12;16(22).
PMID: 31726798 DOI: 10.3390/ijerph16224445

Prolonged exposure to nicotine accelerates onset and progression of renal diseases in habitual cigarette smokers. Exposure to nicotine, either via active or passive smoking is strongly shown to enhance renal oxidative stress and augment kidney failure in various animal models. In this study, we investigated the effects of resveratrol supplementation on nicotine-induced kidney injury and oxidative stress in a rat model. Male Sprague-Dawley rats were given nicotine (0.6 mg/kg, i.p.) alone or in combination with either resveratrol (8 mg/kg, i.p.), or angiotensin II type I receptor blocker, irbesartan (10 mg/kg, p.o.) for 28 days. Upon completion of treatment, kidneys were investigated for changes in structure, kidney injury markers and oxidative stress. Administration of nicotine alone for 28 days resulted in significant renal impairment as shown by marked increase in plasma creatinine, blood urea nitrogen (BUN) and oxidative stress. Co-administration with resveratrol however successfully attenuated these changes, with a concomitant increase in renal antioxidants such as glutathione similar to the conventionally used angiotensin II receptor blocker, irbesartan. These data altogether suggest that targeting renal oxidative stress with resveratrol could alleviate nicotine-induced renal injury. Antioxidants may be clinically important for management of renal function in habitual smokers.

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
Enriched zinc oxide nanoparticles by Nasturtium officinale leaf extract: Joint ultrasound-microwave-facilitated synthesis, characterization, and implementation for diabetes control and bacterial inhibition

Bayrami A, Ghorbani E, Rahim Pouran S, Habibi-Yangjeh A, Khataee A, Bayrami M

Ultrason Sonochem, 2019 Nov;58:104613.
PMID: 31450359 DOI: 10.1016/j.ultsonch.2019.104613

The leaf extract of a medicinally important plant, watercress (Nasturtium officinale), was obtained through an ultrasound-facilitated method and utilized for the preparation of ZnO nanoparticles via a joint ultrasound-microwave assisted procedure. The characteristics of the extract enriched nanoparticles (Ext/ZnO) were determined by SEM, TEM, XRD, EDX, BET, FTIR, TGA, and UV-Vis DRS analyses and compared to that of ZnO prepared in the absence of the extract (ZnO). The presence of carbon and carbonaceous bonds, changes in the morphology, size, band gap energy, and weight-decay percentage were a number of differences between ZnO and Ext/ZnO that confirmed the link of extract over nanoparticles. Ext/ZnO, watercress leaf extract, ZnO, and insulin therapies were administrated to treat alloxan-diabetic Wister rats and their healing effectiveness results were compared to one another. The serum levels of the main diabetic indices such as insulin, fasting blood glucose, and lipid profile (total triglyceride, total cholesterol, and high-density lipoprotein cholesterol) were estimated for healthy, diabetic, and the rats rehabilitated with the studied therapeutic agents. The watercress extract-enriched ZnO nanoparticles offered the best performance and suppressed the diabetic status of rats. Moreover, both ZnO samples satisfactory inhibited the activities of Staphylococcus aureus and Escherichia coli bacteria. Based on the results, the application of Nasturtium officinale leaf extract can strongly empower ZnO nanoparticles towards superior antidiabetic and enhanced antibacterial activities.

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
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
Fulltext The Effects of Tocotrienol on Bone Peptides in a Rat Model of Osteoporosis Induced by Metabolic Syndrome: The Possible Communication between Bone Cells

Wong SK, Chin KY, Ima-Nirwana S

Int J Environ Res Public Health, 2019 09 09;16(18).
PMID: 31505801 DOI: 10.3390/ijerph16183313

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.

Matched MeSH terms: Rats, Wistar
Primary assessment of a T. spiralis putative serine protease for early serological detection of experimental trichinellosis

Sun GG, Lei JJ, Guo KX, Liu RD, Long SR, Zhang X, et al.

Trop Biomed, 2019 Sep 01;36(3):792-802.
PMID: 33597500

A putative serine protease of T. spiralis (TsSP) was expressed in Escherichia coli and its potential as a diagnostic antigen was primarily assessed in this study. Anti-Trichinella IgG in serum samples from T. spiralis different animal hosts (mice, rats, pigs and rabbits) were detected on Western blot analysis with rTsSP. Anti-Trichinella antibodies were detected in 100% (30/30) of experimentally infected mice by rTsSP-ELISA. Cross-reactions of rTsSPELISA were not found with sera from mice infected with other parasites (S. erinaceieuropaei, S. japonicum, C. sinensis, A. cantonensis and T. gondii) and sera from normal mice. There was no statistical difference in antibody detection rate among mice infected with the encapsulated Trichinella species (T. spiralis, T. nativa, T. britovi, and T. nelsoni) (P>0.05). The results of rTsSP-ELISA showed that serum specific antibody IgG in mice infected with 100 or 500 T. spiralis muscle larvae (ML) were detectable early at 7-8 dpi, but not detected by ML ES antigen-ELISA prior to 10-12 dpi. Specific anti-Trichinella IgG was detected in 100% (18/18) of infected pigs by rTsSP-ELISA and ES-ELISA, but no specific antibodies was not detected in 20 conventionally raised normal pigs by two antigens. The results showed the rTsSP had the potential for early serodiagnosis of animal Trichinella infection, however it requires to be assayed with early infection sera of swine infected with Trichinella and other parasites.

Matched MeSH terms: Rats, Wistar
Fulltext The effects of Pandanus amaryllifolius (Roxb.) leaf water extracts on fructose-induced metabolic syndrome rat model

Reshidan NH, Abd Muid S, Mamikutty N

BMC Complement Altern Med, 2019 Aug 28;19(1):232.
PMID: 31462242 DOI: 10.1186/s12906-019-2627-0

BACKGROUND: Metabolic syndrome is a non-communicable disease inclusive of risk factors such as central obesity, hypertension, hyperglycaemia and dyslipidaemia. In this present study, we investigated the ability of Pandanus amaryllifolius (PA) leaf water extract to reverse the cluster of diseases in an established rat model induced by fructose in drinking water.
METHODS: Thirty healthy adult male Wistar rats (150-180 g) were randomly divided into three groups which included control (C; n = 6), PA extract (PAE; n = 6) and Metabolic Syndrome (MetS; n = 18). Food and fluid were given ad libitum for 8 weeks. These groups differed in fluid intake whereby rats received tap water, 10% of PA leaf water extracts and 20% of fructose in drinking water in group C, PAE and MetS, respectively. After 8 weeks, the MetS group was further subdivided into three subgroups namely MetS1 (n = 6), MetS2 (n = 6) and MetS3 (n = 6). The C, PAE and MetS1 were sacrificed. MetS1 group was sacrificed as the control for metabolic syndrome. MetS2 and MetS3 groups were treated with only tap water and 10% of PA leaf water extract respectively for another 8 weeks. The parameters for physiological and metabolic changes such as obesity, hypertension, hyperglycaemia, dyslipidaemia, and inflammatory biomarkers (NFκβ p65, TNFα, leptin and adiponectin) were measured.
RESULTS: The intake of 20% of fructose in drinking water induced full blown of metabolic syndrome symptoms, including obesity, hypertension, dyslipidaemia and hyperglycaemia in male Wistar rats. Subsequently, treatment with PA leaf water extract improved obesity parameters including BMI, abdominal adipose tissue deposition and adipocytes size, systolic and diastolic blood pressures, fasting plasma glucose, triglycerides, high density lipoprotein with neutral effects on inflammatory biomarkers.
CONCLUSIONS: Administration of PA in metabolic syndrome rat model attenuates most of the metabolic syndrome symptoms as well as improves obesity. Therefore, PA which is rich in total flavonoids and total phenolic acids can be suggested as a useful dietary supplement to improve metabolic syndrome components induces by fructose.

Matched MeSH terms: Rats, Wistar
Interspecies and intergender differences in acute toxicity of K-oximes drug candidates

Jaćević V, Nepovimova E, Kuča K

Chem Biol Interact, 2019 Aug 01;308:312-316.
PMID: 31153983 DOI: 10.1016/j.cbi.2019.05.035

K-oximes were developed as modern drug candidates acting as AChE reactivators. In this study, it has been investigated which interspecies and intergender differences changes could be observed in Wistar rats and Swiss mice, both genders, after the treatment with increasing doses of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, and K075. After the 24 h, a number of died animals was counted and the median lethal dose (LD50) for each oxime was calculated. By using the intramuscular route of administration, asoxime and K027 had the least toxicity in female rats (640.21 mg/kg and 686.08 mg/kg), and in female mice (565.75 mg/kg and 565.74 mg/kg), respectively. Moreover, asoxime and K027 showed 3, 4 or 8 times less acute toxicity in comparison to K048, obidoxime and K075, respectively. Beyond, K075 had the greatest toxicity in male rats (81.53 mg/kg), and in male mice (57.34 mg/kg), respectively. Our results can help to predict likely adverse toxic effects, target organ systems and possible outcome in the event of massive human overexposure, and in establishing risk categories or in dose selection for the initial repeated dose toxicity tests to be conducted for each oxime.

Matched MeSH terms: Rats, Wistar
Human bone marrow-derived mesenchymal stromal cells in combination with silymarin regulate hepatocyte growth factor expression and genotoxicity in carbon tetrachloride induced hepatotoxicity in Wistar rats

Aithal AP, Bairy LK, Seetharam RN, Rao MK

J Cell Biochem, 2019 08;120(8):13026-13036.
PMID: 30873677 DOI: 10.1002/jcb.28573

BACKGROUND: To evaluate the antimutagenic potential of combination treatment of human bone marrow-derived mesenchymal stromal cells (BM-MSCs) and silymarin and its effect on hepatocyte growth factor levels in CCl4 induced hepatotoxicity in Wistar rats.
METHODS: Hepatotoxicity was induced in adult female Wistar rats using carbon tetrachloride (CCl4 ). Thirty-six rats were randomly divided into six groups with six rats in each group: Group 1 (normal control group), Group 2 (received only CCl 4 ), Group 3 (CCl 4 +low dose BM-MSCs), Group 4 (CCl 4 +high dose BM-MSCs), Group 5 (CCl 4 + silymarin), Group 6 (CCl 4 +silymarin+high dose BM-MSCs). Thirty days after the treatment, blood samples were collected for hepatocyte growth factor estimation. The rats were then killed, bone marrow was extracted for chromosomal aberration assay. Liver tissue was processed for evaluating the DNA fragmentation assay, histopathology, and scanning electron microscopy study.
RESULTS: Combination treatment of silymarin and high dose BM-MSCs significantly (P

Matched MeSH terms: Rats, Wistar
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
Rosmarinic acid attenuates inflammation in experimentally induced arthritis in Wistar rats, using Freund's complete adjuvant

Gautam RK, Gupta G, Sharma S, Hatware K, Patil K, Sharma K, et al.

Int J Rheum Dis, 2019 Jul;22(7):1247-1254.
PMID: 31155849 DOI: 10.1111/1756-185X.13602

AIM: The purpose of our investigation is to evaluate the anti-arthritic potential of isolated rosmarinic acid from the rind of Punica granatum.
METHOD: Rosmarinic acid was isolated by bioactivity-guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)-induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor-α (TNF-α) were also estimated.
RESULTS: Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P Wistar rats. This study represented the therapeutic role of rosmarinic acid from Punica granatum for the management of arthritis/rheumatoid arthritis/osteoarthritis and related inflammatory complications with negligible side effects which was still far from complete mitigation with available conventional medicines.

Matched MeSH terms: Rats, Wistar
Zingerone (4-(4-hydroxy-3-methylphenyl)butan-2-one) ameliorates renal function via controlling oxidative burst and inflammation in experimental diabetic nephropathy

Rehman MU, Rashid SM, Rasool S, Shakeel S, Ahmad B, Ahmad SB, et al.

Arch Physiol Biochem, 2019 Jul;125(3):201-209.
PMID: 29537332 DOI: 10.1080/13813455.2018.1448422

Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-β. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.

Matched MeSH terms: Rats, Wistar
Fulltext Zinc Supplementation and Ischemia Pre-conditioning in Renal Ischemia/Reperfusion Injury

Mazaheri B, Emami F, Moslemi F, Talebi A, Nematbakhsh M

Malays J Med Sci, 2019 Jul;26(4):39-46.
PMID: 31496892 DOI: 10.21315/mjms2019.26.4.5

Backgrounds: Renal ischemia/reperfusion (RIR) is a major cause of kidney dysfunction in clinic. The main objective of this study was to investigate the effect of pre-conditioning ischemia (IPC) and zinc (Zn) supplementation on renal RIR injury.
Methods: A total of 63 unilateral nephrectomised male and female Wistar rats were divided into five groups. Group 1 (ShOPR): Rats as sham-operated group were subjected to surgical procedure without RIR. Group 2 (Isch): Rats underwent RIR (left kidney ischemia for 30 min followed by 48 h reperfusion). Group 3 (Zn+Isch): Rats were treated as group 2 but they received Zn sulphate (30 mg/kg) 1 h before induction of RIR. Group 4 (IPC+Isch): Rats were treated as group 2 but they underwent 1 min of ischemia followed by 3 min reperfusion as IPC, which was repeated for three times before induction of RIR. Group 5 (Zn+IPC+Isch): Rats were subjected to receive both Zn sulphate and IPC before induction of RIR. Urine samples were collected in the last 6 h of reperfusion, and finally biochemical and histological measurements were performed.
Results: The serum level of creatinine (Cr), normalised kidney weight (KW) and kidney tissue damage score (KTDS) increased by RIR alone significantly (P < 0.05). These parameters were attenuated statistically by Zn supplementation (P < 0.05). However, IPC alone or co-treatment of Zn and IPC did not improve the biochemical and histological markers altered by RIR injury.
Conclusion: Zn supplementation had a protective role against RIR while such protective effect was not observed by IPC alone or by co-treatment of Zn and IPC.

Matched MeSH terms: Rats, Wistar

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