Displaying publications 81 - 100 of 108 in total

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  1. Vattam KK, Raghavendran H, Murali MR, Savatey H, Kamarul T
    Hum Exp Toxicol, 2016 Aug;35(8):893-901.
    PMID: 26429928 DOI: 10.1177/0960327115608246
    In the present study, thirty six male Sprague Dawley rats were randomly divided into six groups and were injected with varying doses of alloxan (Ax) and nicotinamide (NA). The serum levels of glucose, insulin, and adiponectin were measured weekly up to 4 weeks.
    Matched MeSH terms: Kidney/drug effects
  2. Mustafa MR, Dharmani M, Kunheen NK, Sim MK
    Regul. Pept., 2004 Aug 15;120(1-3):15-22.
    PMID: 15177916
    An earlier study showed that des-aspartate-angiotensin I (DAA-I) attenuated the pressor action of angiotensin III in aortic rings of the spontaneously hypertensive rat (SHR) but not the normotensive Wistar Kyoto (WKY) rat. The present study investigated similar properties of DAA-I in isolated perfused kidneys and mesenteric beds of WKY and SHR. In the renal vasculature, angiotensin III induced a dose-dependent pressor response, which was more marked in the SHR than WKY in terms of significant greater magnitude of response and lower threshold. DAA-I attenuated the pressor action of angiotensin III in both the WKY and SHR. The attenuation in SHR was much more marked, occurring at doses as low as 10(-15) M DAA-I, while effective attenuation was only seen with 10(-9) M in WKY. The effects of DAA-I was not inhibited by PD123319 and indomethacin, indicating that its action was not mediated by angiotensin AT2 receptors and prostaglandins. However, the direct pressor action of angiotensin III in the SHR but not the WKY was attenuated by indomethacin suggesting that this notable difference could be due to known decreased response of renal vasculature to vasodilator prostaglandins in the SHR. Pressor responses to angiotensin III in the mesenteric vascular bed was also dose dependent, but smaller in magnitude compared to the renal response. The responses in the SHR, though generally smaller, were not significantly different from those of the WKY. This trend is in line with the similar observations with angiotensin III and II by other investigators. In terms of the effect of DAA-I, indomethacin and PD123319 on angiotensin III action, similar patterns to those of the renal vasculature were observed. This reaffirms that in the perfused kidney and mesenteric bed, where the majority of the vessels are contractile, femtomolar concentrations of DAA-I attenuates the pressor action of angiotensin III. The attenuation is not indomethacin sensitive and does not involve the angiotensin AT2 receptor. The findings suggest that DAA-I possesses protective vascular actions and is involved in the pathophysiology of hypertension.
    Matched MeSH terms: Kidney/drug effects*
  3. Afzal S, Sattar MA, Johns EJ, Abdulla MH, Akhtar S, Hashmi F, et al.
    J Physiol Biochem, 2016 Dec;72(4):593-604.
    PMID: 27405250
    Adiponectin exerts vasodilatory effects. Irbesartan, an angiotensin receptor blocker, possesses partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity and increases circulating adiponectin. This study explored the effect of irbesartan alone and in combination with adiponectin on blood pressure, renal hemodynamic excretory function, and vasoactive responses to angiotensin II and adrenergic agonists in spontaneously hypertensive rat (SHR). Irbesartan was given orally (30 mg/kg/day) for 28 days and adiponectin intraperitoneally (2.5 μg/kg/day) for last 7 days. Groups of SHR received either irbesartan or adiponectin or in combination. A group of Wistar Kyoto rats (WKY) served as controls. Metabolic data and plasma samples were taken on days 0, 21, and 28. In acute studies, the renal vasoconstrictor actions of angiotensin II (ANGII), noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) were determined. SHR control rats had a higher mean blood pressure than the WKY (132 ± 7 vs. 98 ± 2 mmHg), lower plasma and urinary adiponectin, creatinine clearance, urine flow rate and sodium excretion, and oxidative stress markers compared to WKY (all P drug treatments and to a greater extent by combined treatment. Responses to intrarenal administration of NA, PE, ME, and ANGII were larger in SHR (P 
    Matched MeSH terms: Kidney/drug effects*
  4. Subramaniyan V, Shaik S, Bag A, Manavalan G, Chandiran S
    Pak J Pharm Sci, 2018 Mar;31(2):509-516.
    PMID: 29618442
    To determine the ameliorative potential of the active fraction from different extracts of Rumex vesicarius against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats and its possible mechanism of action. Both sex wistar rats were divided into 6 groups (n=6/group) were fed with a control, potassium dichromate and gentamicin supplemented with different extracts at the doses of 200 and 400mg/kg respectively. Oral administration of EERV offered a significant (p<0.01 and p<0.001) dose dependent protection against PD and GN induced nephrotoxicity. Potassium dichromate and gentamicin nephrotoxicity assessed in terms of body weight, kidney weight, creatinine, urea, uric acid, BUN, albumin and total protein. Thus the present study revealed that EERV phytochemical constituents play an important role in protection against kidney damage.
    Matched MeSH terms: Kidney/drug effects
  5. Singh GD, Ganjoo M, Youssouf MS, Koul A, Sharma R, Singh S, et al.
    Food Chem Toxicol, 2009 Oct;47(10):2661-5.
    PMID: 19654032 DOI: 10.1016/j.fct.2009.07.031
    Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as "Kacip Fatimah". Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women's health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns.
    Matched MeSH terms: Kidney/drug effects
  6. Shah MD, Iqbal M
    Food Chem Toxicol, 2010 Dec;48(12):3345-53.
    PMID: 20828599 DOI: 10.1016/j.fct.2010.09.003
    Diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphoro thioate), an organo-phosphate insecticide, has been used worldwide in agriculture and domestic for several years, which has led to a variety of negative effects in non target species including humans. However, its nephrotoxic effects and mechanism of action has not been fully elucidated so far. Therefore, the present study was aimed at evaluating the nephrotoxic effects of diazinon and its mechanism of action with special reference to its possible ROS generating potential in rats. Treatment of rats with diazinon significantly enhances renal lipid peroxidation which is accompanied by a decrease in the activities of renal antioxidant enzymes (e.g. catalase, glutathione peroxidise, glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione S-transferase) and depletion in the level of glutathione reduced. In contrast, the activities of renal γ-glutamyl transpeptidase and quinone reductase were increased. Parallel to these changes, diazinon treatment enhances renal damage as evidenced by sharp increase in blood urea nitrogen and serum creatinine. Additionally, the impairment of renal function corresponds histopathologically. In summary, our results indicate that diazinon treatment eventuates in decreased renal glutathione reduced, a fall in the activities of antioxidant enzymes including the enzymes involved in glutathione metabolism and excessive production of oxidants with concomitant renal damage, all of which are involved in the cascade of events leading to diazinon-mediated renal oxidative stress and toxicity. We concluded that in diazinon exposure, depletion of antioxidant enzymes is accompanied by induction of oxidative stress that might be beneficial in monitoring diazinon toxicity.
    Matched MeSH terms: Kidney/drug effects
  7. Hiong LC, Voon KL, Abdullah NA, Sattar MA, Rahman NA, Khan AH, et al.
    Acta Pharmacol Sin, 2008 Apr;29(4):451-7.
    PMID: 18358091 DOI: 10.1111/j.1745-7254.2008.00772.x
    The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-beta1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF).
    Matched MeSH terms: Kidney/drug effects
  8. Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Abdullah NA, et al.
    Can J Physiol Pharmacol, 2014 Dec;92(12):1029-35.
    PMID: 25403946 DOI: 10.1139/cjpp-2014-0236
    This study investigated the role of α1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar-Kyoto (WKY) rats with isoprenaline (5.0 mg · (kg body mass)(-1), by subcutaneous injection every 72 h) and caffeine (62 mg · L(-1) in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY 7378, a selective α1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P < 0.05). In the LVH group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P < 0.05), compared with the control group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY 7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the α1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state.
    Matched MeSH terms: Kidney/drug effects
  9. Balakumar P, WitnessKoe WE, Gan YS, JemayPuah SM, Kuganesswari S, Prajapati SK, et al.
    Regul Toxicol Pharmacol, 2017 Mar;84:35-44.
    PMID: 27993652 DOI: 10.1016/j.yrtph.2016.12.007
    This study investigated the pretreatment and post-treatment effects of dipyridamole (20 mg/kg/day, p.o.) in gentamicin-induced acute nephrotoxicity in rats. Rats were administered gentamicin (100 mg/kg/day, i.p.) for 8 days. Gentamicin-administered rats exhibited renal structural and functional changes as assessed in terms of a significant increase in serum creatinine and urea and kidney weight to body weight ratio as compared to normal rats. Renal histopathological studies revealed a marked incidence of acute tubular necrosis in gentamicin-administered rats. These renal structural and functional abnormalities in gentamicin-administered rats were accompanied with elevated serum uric acid level, and renal inflammation as assessed in terms of decrease in interleukin-10 levels. Dipyridamole pretreatment in gentamicin-administered rats afforded a noticeable renoprotection by markedly preventing renal structural and functional abnormalities, renal inflammation and serum uric acid elevation. On the other hand, dipyridamole post-treatment did not significantly prevent uric acid elevation and renal inflammation, and resulted in comparatively less protection on renal function although it markedly reduced the incidence of tubular necrosis. In conclusion, uric acid elevation and renal inflammation could play key roles in gentamicin-nephrotoxicity. Dipyridamole pretreatment markedly prevented gentamicin-induced acute nephrotoxicity, while its post-treatment resulted in comparatively less renal functional protection.
    Matched MeSH terms: Kidney/drug effects*
  10. Ching JJ, Shuib AS, Abdullah N, Majid NA, Taufek NM, Sutra J, et al.
    Fish Shellfish Immunol, 2021 Sep;116:61-73.
    PMID: 34157396 DOI: 10.1016/j.fsi.2021.06.005
    In aquaculture, commercial fish such as red hybrid tilapia are usually raised at high density to boost the production within a short period of time. This overcrowded environment, however, may cause stress to the cultured fish and increase susceptibility to infectious diseases. Antibiotics and chemotherapeutics are used by fish farmers to overcome these challenges, but this may increase the production cost. Studies have reported on the potential of mushroom polysaccharides that can act as immunostimulants to enhance the immune response and disease resistance in fish. In the current study, hot water extract (HWE) from mushroom stalk waste (MSW) was used to formulate fish feed and hence administered to red hybrid tilapia to observe the activation of immune system. Upon 30 days of feeding, the fish were challenged with pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (poly (I:C)) to mimic bacterial and viral infection, respectively. HWE supplementation promoted better feed utilisation in red hybrid tilapia although it did not increase the body weight gain and specific growth rate compared to the control diet. The innate immunological parameters such as phagocytic activity and respiratory burst activity were significantly higher in HWE-supplemented group than that of the control group following PAMPs challenges. HWE-supplemented diet also resulted in higher mRNA transcription of il1b and tnfa in midgut, spleen and head kidney at 1-day post PAMPs injection. Tlr3 exhibited the highest upregulation in the HWE fed fish injected with poly (I:C). At 3-days post PAMPs injection, both ighm and tcrb expression were upregulated significantly in the spleen and head kidney. Results showed that HWE supplementation enhances the immune responses of red hybrid tilapia and induced a higher serum bactericidal activity against S. agalactiae.
    Matched MeSH terms: Head Kidney/drug effects
  11. Tan SMQ, Chiew Y, Ahmad B, Kadir KA
    Nutrients, 2018 Sep 17;10(9).
    PMID: 30227659 DOI: 10.3390/nu10091315
    Tocotrienol-rich vitamin E from palm oil (Tocovid) has been shown to ameliorate diabetes through its superior antioxidant, antihyperglycemic, and anti-inflammatory properties in diabetic rats. This study aimed to investigate the effects of Tocovid on diabetic nephropathy in patients with type 2 diabetes. Baseline parameters of potential subjects such as HbA1c, blood pressure, Advanced Glycation Endproduct (AGE), soluble receptor for AGE (sRAGE), Nε-Carboxymethyllysine (Nε-CML), and Cystatin C were assessed for possible correlation with diabetic nephropathy. Only subjects with diabetic nephropathy or urine microalbuminuria-positive defined as Urine Albumin to Creatinine Ratio (UACR) >10 mg/mmol were recruited into a prospective, randomized, double-blinded, placebo-controlled trial. The intervention group (n = 22) received Tocovid 200 mg twice a day while the control group (n = 23) received placebo twice a day for 8 weeks. Changes in Hemoglobin A1c (HbA1c), blood pressure, serum biomarkers and renal parameters such as UACR, serum creatinine, and estimated Glomerular Filtration Rate (eGFR) were compared between the two groups. It was found that serum Nε-CML significantly correlated to the severity of microalbuminuria. For every 1 ng/mL increase in serum Nε-CML, the odds of diabetic nephropathy increased by 1.476 times. Tocovid, compared to placebo, significantly reduced serum creatinine but not eGFR, UACR, HbA1c, blood pressure, and serum biomarkers. In conclusion, serum Nε-CML is a potential biomarker for diabetic nephropathy. Treatment with Tocovid significantly reduced serum creatinine; therefore Tocovid may be a useful addition to the current treatment for diabetic nephropathy.
    Matched MeSH terms: Kidney/drug effects*
  12. 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: Kidney/drug effects*
  13. Hashim H, Mughrabi FF, Ameen M, Khaledi H, Ali HM
    Molecules, 2012 Aug 03;17(8):9306-20.
    PMID: 22864239 DOI: 10.3390/molecules17089306
    Indolic compounds have attracted a lot of attention due to their interesting biological properties. The present study was performed to evaluate the subacute toxicity and anti-ulcer activity of BClHC against ethanol-induced gastric ulcers. Experimental animal groups were orally pre-treated with different doses of BClHC (50, 100, 200 and 400 mg/kg) in 10% Tween 20 solution (vehicle). Blank and ulcer control groups were pre-treated with vehicle. The positive group was orally pretreated with 20 mg/kg omeprazole. After one hour, all groups received absolute ethanol (5 mL/kg) to generate gastric mucosal injury except the blank control group which was administered the vehicle solution. After an additional hour, all rats were sacrificed, and the ulcer areas of the gastric walls determined. Grossly, the ulcer control group exhibited severe mucosal injury, whereas pre-treatment with either derivative or omeprazole resulted in significant protection of gastric mucosal injury. Flattening of gastric mucosal folds was also observed in rats pretreated with BClHC. Histological studies of the gastric wall of ulcer control group revealed severe damage of gastric mucosa, along with edema and leucocytes infiltration of the submucosal layer compared to rats pre-treated with either BClHC or omeprazole where there were marked gastric protection along with reduction or absence of edema and leucocytes infiltration of the submucosal layer. Subacute toxicity study with a higher dose of derivative (5 g/kg) did not manifest any toxicological signs in rats. In conclusions, the present finding suggests that benzyl N'-(5-chloroindol-3-ylmethylidene)hydrazinecarbodithioate promotes ulcer protection as ascertained by the comparative decreases in ulcer areas, reduction of edema and leucocytes infiltration of the submucosal layer.
    Matched MeSH terms: Kidney/drug effects
  14. Wada T, Mori-Anai K, Kawaguchi Y, Katsumata H, Tsuda H, Iida M, et al.
    J Diabetes Investig, 2022 Jan;13(1):54-64.
    PMID: 34212533 DOI: 10.1111/jdi.13624
    AIMS/INTRODUCTION: The sodium-glucose cotransporter 2 inhibitor, canagliflozin, reduced kidney failure and cardiovascular events in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. We carried out a post-hoc analysis to evaluate the efficacy and safety of canagliflozin in a subgroup of participants in East and South-East Asian (EA) countries who are at high risk of renal complications.

    MATERIALS AND METHODS: Participants with an estimated glomerular filtration rate of 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of >300-5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre-specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants.

    RESULTS: Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end-stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35-0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non-EA participants.

    CONCLUSIONS: In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events.

    Matched MeSH terms: Kidney/drug effects
  15. Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P
    Molecules, 2013 Jan 04;18(1):666-81.
    PMID: 23292329 DOI: 10.3390/molecules18010666
    Mitragynine (MG) is the major active alkaloid found in Mitragyna speciosa Korth. In the present study, we investigated the enhancement of analgesic action of MG when combined with morphine and the effect of the combination on the development of tolerance towards morphine. Mice were administered intraperitoneally with a dose of MG (15 and 25 mg/kg b.wt) combined with morphine (5 mg/kg b.wt) respectively for 9 days. The antinociceptive effect was evaluated by a hot plate test. The protein expression of cyclic adenosine monophosphate (cAMP) and cAMP response element binding (CREB) was analyzed by immunoblot. Toxicological parameters especially liver and kidney function tests were assessed after the combination treatment with MG and morphine. The concurrent administration of MG and morphine showed significant (p < 0.05) increase in latency time when compared to morphine alone group and the outstanding analgesic effects in the combination regimens were maintained until day 9. For the protein expression, there was a significant increment of cAMP and CREB levels (p < 0.05) in group treated with 5 mg/kg morphine but there was no significant change of these protein expressions when MG was combined with morphine. There was a significant changes in toxicological parameters of various treated groups. The combination treatment of MG and morphine effectively reduce the tolerance due to the chronic administration of morphine.
    Matched MeSH terms: Kidney/drug effects
  16. Joshi K, Boettiger D, Kerr S, Nishijima T, Van Nguyen K, Ly PS, et al.
    Pharmacoepidemiol Drug Saf, 2018 Nov;27(11):1209-1216.
    PMID: 30246898 DOI: 10.1002/pds.4657
    PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia.

    METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).

    RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.

    CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

    Matched MeSH terms: Kidney/drug effects*
  17. Nandini C, Madhunapantula SV, Bovilla VR, Ali M, Mruthunjaya K, Santhepete MN, et al.
    J Ethnopharmacol, 2021 Jul 15;275:114074.
    PMID: 33831466 DOI: 10.1016/j.jep.2021.114074
    ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya leaf juice/decoction has been in use in folk medicine in Srilanka, Malaysia and in few parts of India for enhancing the platelet counts in dengue. In Siddha medicine, a traditional form of medicine in India, papaya leaf juice has been used for increasing the platelet counts. Papaya leaf has been reported to enhance blood volume in ancient Ayurveda books in India. Carica papaya leaf is well known for its platelet enhancement activity. Although many preclinical and clinical studies have demonstrated the ability of papaya leaf juice for platelet enhancement, but the underlying mechanisms are still unclear.

    AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp).

    MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting.

    RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/μL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/μL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats.

    CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.

    Matched MeSH terms: Kidney/drug effects
  18. Wang S, Tan KS, Beng H, Liu F, Huang J, Kuai Y, et al.
    Pharmacol Res, 2021 Oct;172:105781.
    PMID: 34302975 DOI: 10.1016/j.phrs.2021.105781
    Sepsis is a severe inflammatory disorder that can lead to multiple organ injury. Isosteviol sodium (STV-Na) is a terpenoid derived from stevioside that exerts anti-inflammatory, antioxidant and antiapoptotic activities. However, the influence of STV-Na on sepsis remains unknown. Here, we assessed the potential effects of STV-Na on sepsis and multiple organ injury induced by lipopolysaccharide (LPS). We found that STV-Na increased the survival rate of mice treat with LPS, significantly improved the functions of the heart, lung, liver, and kidney, reduced the production of inflammatory cytokines and decreased macrophage infiltration. Moreover, Multiorgan metabolomics analysis demonstrated that glutathione metabolism, purine metabolism, glycerophospholipid metabolism and pantothenate and CoA biosynthesis, were significantly altered by STV-Na. This study provides novel insights into the metabolite changes of multiple organ injury in septic mice, which may help characterize the underlying mechanism and provide an improved understanding of the therapeutic effects of STV-Na on sepsis.
    Matched MeSH terms: Kidney/drug effects
  19. Al-Zuaidy MH, Mumtaz MW, Hamid AA, Ismail A, Mohamed S, Razis AFA
    BMC Complement Altern Med, 2017 Jul 10;17(1):359.
    PMID: 28693595 DOI: 10.1186/s12906-017-1849-2
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract.

    METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.

    RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.

    CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.

    Matched MeSH terms: Kidney/drug effects
  20. Fernando HA, Chandramouli C, Rosli D, Lam YL, Yong ST, Yaw HP, et al.
    Nutrients, 2014 Nov 04;6(11):4856-71.
    PMID: 25375630 DOI: 10.3390/nu6114856
    Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time.
    Matched MeSH terms: Kidney/drug effects
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