Displaying publications 1 - 20 of 83 in total

  1. Abdullah R, Alhusainy W, Woutersen J, Rietjens IM, Punt A
    Food Chem. Toxicol., 2016 Jun;92:104-16.
    PMID: 27016491 DOI: 10.1016/j.fct.2016.03.017
    Aristolochic acids are naturally occurring nephrotoxins. This study aims to investigate whether physiologically based kinetic (PBK) model-based reverse dosimetry could convert in vitro concentration-response curves of aristolochic acid I (AAI) to in vivo dose response-curves for nephrotoxicity in rat, mouse and human. To achieve this extrapolation, PBK models were developed for AAI in these different species. Subsequently, concentration-response curves obtained from in vitro cytotoxicity models were translated to in vivo dose-response curves using PBK model-based reverse dosimetry. From the predicted in vivo dose-response curves, points of departure (PODs) for risk assessment could be derived. The PBK models elucidated species differences in the kinetics of AAI with the overall catalytic efficiency for metabolic conversion of AAI to aristolochic acid Ia (AAIa) being 2-fold higher for rat and 64-fold higher for mouse than human. Results show that the predicted PODs generally fall within the range of PODs derived from the available in vivo studies. This study provides proof of principle for a new method to predict a POD for in vivo nephrotoxicity by integrating in vitro toxicity testing with in silico PBK model-based reverse dosimetry.
    Matched MeSH terms: Kidney/drug effects*
  2. Mohd Redzwan S, Rosita J, Mohd Sokhini AM, Nurul 'Aqilah AR, Wang JS, Kang MS, et al.
    Int J Hyg Environ Health, 2014 Apr-May;217(4-5):443-51.
    PMID: 24095591 DOI: 10.1016/j.ijheh.2013.08.007
    Aflatoxin is ubiquitously found in many foodstuffs and produced by Aspergillus species of fungi. Of many aflatoxin metabolites, AFB1 is classified by the International Agency for Research on Cancer (IARC) as group one carcinogen and linked to the development of hepatocellular carcinoma (HCC). The study on molecular biomarker of aflatoxin provides a better assessment on the extent of human exposure to aflatoxin. In Malaysia, the occurrences of aflatoxin-contaminated foods have been documented, but there is a lack of data on human exposure to aflatoxin. Hence, this study investigated the occurrence of AFB1-lysine adduct in serum samples and its association with liver and kidney functions. 5ml fasting blood samples were collected from seventy-one subjects (n=71) for the measurement of AFB1-lysine adduct, albumin, total bilirubin, AST (aspartate aminotransferase), ALT (alanine transaminase), ALP (alkaline phosphatase), GGT (gamma-glutamyl transpeptidase), creatinine and BUN (blood urea nitrogen). The AFB1-lysine adduct was detected in all serum samples (100% detection rate) with a mean of 6.85±3.20pg/mg albumin (range: 1.13-18.85pg/mg albumin). Male subjects (mean: 8.03±3.41pg/mg albumin) had significantly higher adduct levels than female subjects (mean: 5.64±2.46pg/mg albumin) (p<0.01). It was noteworthy that subjects with adduct levels greater than average (>6.85pg/mg albumin) had significantly elevated level of total bilirubin (p<0.01), GGT (p<0.05) and creatinine (p<0.01). Nevertheless, only the level of total bilirubin, (r=0.347, p-value=0.003) and creatinine (r=0.318, p-value=0.007) showed significant and positive correlation with the level of AFB1-lysine adduct. This study provides a valuable insight on human exposure to aflatoxin in Malaysia. Given that aflatoxin can pose serious problem to the health, intervention strategies should be implemented to limit/reduce human exposure to aflatoxin. Besides, a study with a big sample size should be warranted in order to assess aflatoxin exposure in the general population of Malaysia.
    Matched MeSH terms: Kidney/drug effects*
  3. Ruszymah BH, Zaiton Z, Aminuddin S, Khalid BA
    Exp. Clin. Endocrinol. Diabetes, 2001;109(4):227-30.
    PMID: 11453035
    The aim of this study was to investigate the effect of altered thyroid status on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD type 1) and type 2 (11beta-HSD type 2) bioactivity in rat kidney and colon. Male Sprague-Dawley rats (250 g) were treated with either L-thyroxine (T4) or propylthiouracil (PTU) for 4 weeks. Blood were then analysed for serum thyroxine, sodium (Na+) and potassium (K+). The kidneys and colon were assayed for 11beta-HSD type 1 and 11beta-HSD type 2 bioactivity. In T4 treated rats the serum thyroxine was significantly elevated (p<0.05) whilst PTU decreased serum thyroxine significantly (p<0.001) compared to controls. Serum Na+ and K+ were within normal limits. There were no significant changes in 11beta-HSD type 1 bioactivity in both treatment groups compared to controls. However, the 11beta-HSD type 2 bioactivity in rats given thyroxine was significantly higher in the colon (p<0.003) compared to controls. We conclude that altered thyroid status had no effect on 11beta-HSD type 1 bioactivity but 11beta-HSD type 2 bioactivity was elevated in the colon of rats given supplementary thyroxine.
    Matched MeSH terms: Kidney/drug effects*
  4. Kalra J, Prakash A, Kumar P, Majeed AB
    J Renin Angiotensin Aldosterone Syst, 2015 Sep;16(3):459-68.
    PMID: 25944853 DOI: 10.1177/1470320315583582
    Work on the brain renin-angiotensin system has been explored by various researchers and has led to elucidation of its basic physiologies and behavior, including its role in reabsorption and uptake of body fluid, blood pressure maintenance with angiotensin II being its prominent effector. Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects accounting for maintenance of cerebral blood flow and cerebroprotection, seizure, in the etiology of Alzheimer's disease, Parkinson's disease, multiple sclerosis, and bipolar disorder. In this review, we have discussed the distribution of angiotensin receptor subtypes in the central nervous system (CNS) together with enzymatic pathways leading to active angiotensin ligands and its interaction with angiotensin receptor 2 (AT2) and Mas receptors. Secondly, the use of angiotensin analogues (angiotensin converting enzyme inhibitors and AT1 and/or AT2 receptor blockers) in the treatment and management of the CNS disorders mentioned above has been discussed.
    Matched MeSH terms: Kidney/drug effects*
  5. Ngen CC, Cheong IK
    Med. J. Malaysia, 1989 Sep;44(3):199-203.
    PMID: 2626134
    Ten patients on long term lithium therapy (mean four years, range 1-10.5 years) were subjected to various renal, thyroid, haematological, cardiac and endocrine tests. There was impaired urinary concentrating ability in seven subjects, which was not responsive to vasopressin stimulation, suggesting a partial nephrogenic diabetes insipidus. Nine subjects had metabolic acidosis with higher urinary pH than expected suggesting presence of acidification defect in the kidney. No significant change in renal function, thyroid function, ECG or haematological parameters were detected. Our findings concur with previous reports from the West regarding the safety of lithium administration.
    Matched MeSH terms: Kidney/drug effects
  6. Ridzwan BH, Waton NG, Rozali BO, Jais AM, Maimun AH
    PMID: 1982866
    1. In vitro studies of non-specific histidine decarboxylase activity was low or absent in control guinea-pigs and unchanged 9 or 27 hr after chlorpromazine (CPZ) injection intraperitoneally. 2. However, specific histidine decarboxylase activity was found in the control tissues and was increased 9 hr but not 27 hr after CPZ injection.
    Matched MeSH terms: Kidney/drug effects
  7. Rajandram R, Yap NY, Ong TA, Mun KS, Mohamad Wali HA, Hasan MS, et al.
    Malays J Pathol, 2017 Apr;39(1):47-53.
    PMID: 28413205 MyJurnal
    INTRODUCTION: In recent years, prolonged ketamine abuse has been reported to cause urinary tract damage. However, there is little information on the pathological effects of ketamine from oral administration. We aimed to study the effects of oral ketamine on the urinary tract and the reversibility of these changes after cessation of ketamine intake.

    METHODS: Rats were fed with illicit (a concoction of street ketamine) ketamine in doses of 100 (N=12), or 300 mg/kg (N=12) for four weeks. Half of the rats were sacrificed after the 4-week feeding for necropsy. The remaining rats were taken off ketamine for 8 weeks to allow for any potential recovery of pathological changes before being sacrificed for necropsy. Histopathological examination was performed on the kidney and urinary bladder.

    RESULTS: Submucosal bladder inflammation was seen in 67% of the rats fed with 300 mg/kg illicit ketamine. No bladder inflammation was observed in the control and 100 mg/kg illicit ketamine groups. Renal changes, such as interstitial nephritis and papillary necrosis, were observed in rats given illicit ketamine. After ketamine cessation, no inflammation was observed in the bladder of all rats. However, renal inflammation remained in 60% of the rats given illicit ketamine. No dose-effect relationship was established between oral ketamine and changes in the kidneys.

    CONCLUSION: Oral ketamine caused pathological changes in the urinary tract, similar to that described in exposure to parenteral ketamine. The changes in the urinary bladder were reversible after short-term exposure.

    Matched MeSH terms: Kidney/drug effects
  8. Tanvir EM, Afroz R, Chowdhury M, Gan SH, Karim N, Islam MN, et al.
    Hum Exp Toxicol, 2016 Sep;35(9):991-1004.
    PMID: 26519480 DOI: 10.1177/0960327115614384
    This study investigated the main target sites of chlorpyrifos (CPF), its effect on biochemical indices, and the pathological changes observed in rat liver and kidney function using gas chromatography/mass spectrometry. Adult female Wistar rats (n = 12) were randomly assigned into two groups (one control and one test group; n = 6 each). The test group received CPF via oral gavage for 21 days at 5 mg/kg daily. The distribution of CPF was determined in various organs (liver, brain, heart, lung, kidney, ovary, adipose tissue, and skeletal muscle), urine and stool samples using GCMS. Approximately 6.18% of CPF was distributed in the body tissues, and the highest CPF concentration (3.80%) was found in adipose tissue. CPF also accumulated in the liver (0.29%), brain (0.22%), kidney (0.10%), and ovary (0.03%). Approximately 83.60% of CPF was detected in the urine. CPF exposure resulted in a significant increase in plasma transaminases, alkaline phosphatase, and total bilirubin levels, a significant reduction in total protein levels and an altered lipid profile. Oxidative stress due to CPF administration was also evidenced by a significant increase in liver malondialdehyde levels. The detrimental effects of CPF on kidney function consisted of a significant increase in plasma urea and creatinine levels. Liver and kidney histology confirmed the observed biochemical changes. In conclusion, CPF bioaccumulates over time and exerts toxic effects on animals.
    Matched MeSH terms: Kidney/drug effects*
  9. Arya A, Al-Obaidi MM, Shahid N, Bin Noordin MI, Looi CY, Wong WF, et al.
    Food Chem. Toxicol., 2014 Sep;71:183-96.
    PMID: 24953551 DOI: 10.1016/j.fct.2014.06.010
    The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.
    Matched MeSH terms: Kidney/drug effects*
  10. Koriem KM, Arbid MS, Asaad GF
    J Nat Med, 2013 Jan;67(1):159-67.
    PMID: 22484604 DOI: 10.1007/s11418-012-0667-6
    The kidney is one of the critical target organs for chronic cadmium toxicity. Cadmium is a cumulative nephrotoxicant, and preferentially accumulates and persists in the kidneys. The natriuretic and antidiuretic effects of methyl alcohol extracts of Chelidonium majus L. (C. majus) leaves were evaluated in kidney of cadmium-intoxicated rats. Ninety-six male Sprague-Dawley Albino rats were divided into two major groups (toxicity and biochemical, 60 and 36 rats, respectively). There was a decrease in kidney weight and serum electrolytes, but an increase in urinary volume, excretion of electrolytes, serum urea and creatinine, after 9 weeks of cadmium chloride intoxication. Treatment of C. majus methyl alcohol extract for 10 weeks starting 1 week before cadmium administration shifted the above parameters towards the normal values. These results were supported by molecular and histological investigations. Treatment with C. majus methyl alcohol extract has natriuretic and antidiuretic effects against cadmium-induced nephrotoxicity in rats.
    Matched MeSH terms: Kidney/drug effects*
  11. Mailankot M, Jayalekshmi H, Chakrabarti A, Alang N, Vasudevan DM
    Indian J. Exp. Biol., 2009 Jul;47(7):608-10.
    PMID: 19761047
    Ethanol intoxication resulted in high extent of lipid peroxidation, and reduction in antioxidant defenses (decreased GSH, GSH/GSSG ratio, and catalase, SOD and GPx activities) and (Na+/K+)-ATPase activity in kidney. Alpha-tocopherol treatment effectively protected kidney from ethanol induced oxidative challenge and improved renal (Na+/K+)-ATPase activity. Ethanol induced oxidative stress in the kidney and decreased (Na+/K+)-ATPase activity could be reversed by treatment with ascorbic acid.
    Matched MeSH terms: Kidney/drug effects*
  12. Go KW, Teo SM
    Med. J. Malaysia, 2006 Oct;61(4):447-50.
    PMID: 17243522
    Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease with renal involvement being one of the most frequent and serious manifestations of the disease. The aim of the study is to analyze the treatment and renal outcome of patients with lupus nephritis (LN) WHO class III and IV on cyclophosphamide (CYC). We retrospectively identified 41 patients with biopsy proven LN who was given either oral or intravenous CYC. The male: female ratio was 4:37; with a mean age of 31.7 +/- 9.8 years at presentation. 36 patients (87.8%) had LN class IV and only five patients (12.2%) with LN class III. The mean serum creatinine at presentation was 87.4 +/- 37.2 micromol/L with mean follow-up of 84 +/- 78 months. A total of 30 patients (73.2%) completed 12 courses of IV CYC and one patient (2.4%) completed three months of oral CYC. 71.0% (n = 22) had complete response (CR), 25.8% (n = 8) had partial response and 3.2% (n = 1) had no response (NR). Of the remaining 11 patients, two patients (4.9%) died during the treatment, three patients (7.3%) defaulted treatment and five patients (12.2%) are still receiving ongoing treatment. Presence of hypertension (p < 0.003) and evidence of chronicity on renal biopsy (p < 0.016) were significantly correlated with the progressive deterioration of renal function in our population. In conclusion, hypertension and evidence of chronicity on renal biopsy, proved to be risk factors for progressive renal impairment in our study population. The achieved global outcome can be considered good.
    Study site: Hospital Ipoh, Ipoh, Perak, Malaysia
    Matched MeSH terms: Kidney/drug effects*
  13. bin Long I, Singh HJ, Rao GJ
    J. Pharmacol. Sci., 2005 Nov;99(3):272-6.
    PMID: 16293937
    The effects of indomethacin and nabumetone on urine and electrolyte excretion in conscious rats were examined. Male Sprague-Dawley rats were housed individually for a five-week duration, consisting of acclimatization, control, experimental, and recovery phases. During the experimental phase, rats were given either indomethacin (1.5 mg . kg(-1) body weight . day(-1) in 0.5 ml saline, n = 10), nabumetone (15 mg . kg(-1) body weight . day(-1) 0.5 ml saline, n = 10), or 0.5 ml saline alone (n = 10) for a period of two weeks. Water and food intake, body weight, urine output, and electrolyte excretions were estimated. Data were analyzed using two-way ANOVA. Urine output in the indomethacin- and nabumetone-treated groups was not different from the controls, but was significantly different between the drug-treated groups (P<0.01). Sodium, potassium, calcium, and magnesium excretions were not different between nabumetone-treated and control rats. However, sodium and potassium excretion was significantly lower in rats receiving indomethacin when compared to the control rats. Calcium and magnesium outputs, although did not differ from the controls, nevertheless decreased significantly with indomethacin (P<0.01). It appears that indomethacin and nabumetone when given at maximum human therapeutic doses may affect urine and electrolyte output in conscious rats.
    Matched MeSH terms: Kidney/drug effects*
  14. Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S
    Int J Mol Sci, 2011;12(1):829-43.
    PMID: 21340016 DOI: 10.3390/ijms12010829
    Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys.
    Matched MeSH terms: Kidney/drug effects*
  15. Pour BM, Latha LY, Sasidharan S
    Molecules, 2011 May 03;16(5):3663-74.
    PMID: 21540795 DOI: 10.3390/molecules16053663
    BACKGROUND: The objective of this study was to investigate the toxicity of Lantana camara methanol extract.

    METHODS: In order to evaluate the toxicity of Lantana camara, the acute toxicity of the methanolic extract on adult mice and cytotoxicity test on Vero cell line were investigated. A fixed large dose of 2 g/kg body weight of L. camara leaf extract was administrated by a single oral gavage according to the OECD procedure.

    RESULTS: In 2 weeks, L. camara leaf extract showed no obvious acute toxicity. While female mice lost body weight after being treated with single dose of leaf extract in acute toxicity test, male ones lost organ mass, particularly for heart and kidney. The biochemical liver function tests showed significantly elevated TBIL and ALT in the L. camara leaf extract treated female mice group compared with the control group. Cytotoxicity effect of leaf extract of L. camara was estimated through a MTT assay. Cytotoxicity tests on Vero cell line disclosed that leaf extract at concentrations up to 500 µg/mL inhibited the growth of cells 2.5 times less than did Triton 100 × 1%. More interestingly, the cytotoxicity initiated to decline at elevated concentrations of this extract.

    CONCLUSIONS: The results of both tests confirm that L. camara shows a pro toxic effect.

    Matched MeSH terms: Kidney/drug effects
  16. Nassar I, Pasupati T, Judson JP, Segarra I
    Malays J Pathol, 2010 Jun;32(1):1-11.
    PMID: 20614720 MyJurnal
    Imatinib, a selective tyrosine kinase inhibitor, is the first line treatment against chronic myelogenous leukaemia (CML) and gastrointestinal stromal tumors (GIST). Several fatal cases have been associated with imatinib hepatotoxicity. Acetaminophen, an over-the-counter analgesic, anti-pyretic drug, which can cause hepatotoxicity, is commonly used in cancer pain management. We assessed renal and hepatic toxicity after imatinib and acetaminophen co-administration in a preclinical model. Four groups of male ICR mice (30-35 g) were fasted overnight and administered either saline solution orally (baseline control), imatinib 100 mg/kg orally (control), acetaminophen 700 mg/kg intraperitoneally (positive control) or co-administered imatinib 100 mg/kg orally and acetaminophen 700 mg/kg intraperitoneally (study group), and sacrificed at 15 min, 30 min, 1 h, 2 h, 4 h and 6 h post-administration (n = 4 per time point). The liver and kidneys were harvested for histopathology assessment. The liver showed reversible cell damage like feathery degeneration, microvesicular fatty change, sinusoidal congestion and pyknosis, when imatinib or acetaminophen were administered separately. The damage increased gradually with time, peaked at 2 h but resolved by 4 h. When both drugs were administered concurrently, the liver showed irreversible damage (cytolysis, karyolysis and karyorrhexis) which did not resolve by 6 h. Very minor renal changes were observed. Acetaminophen and imatinib co-administration increased hepatoxicity which become irreversible, probably due to shared P450 biotransformation pathways and transporters in the liver.
    Matched MeSH terms: Kidney/drug effects*
  17. Shamaan NA, Wan Ngah WZ, Ibrahim R, Jarien Z, Top AG, Abdul Kadir K
    Biochem. Pharmacol., 1993 Apr 06;45(7):1517-9.
    PMID: 8471073
    The effect of tocotrienol on the activities of glutathione S-transferases (GSTs), glutathione reductase (GR) and glutathione peroxidase (GPx) in rats given 2-acetylaminofluorene (AAF) was investigated over a 20 week period. Liver and kidney GST and liver GR activities were significantly increased after AAF administration. Kidney GPx activities were significantly affected; activity assayed with cumene hydroperoxide (cu-OOH) was increased but activity assayed with H2O2 was reduced. Supplementation of the diet with tocotrienol in the AAF-treated rats reduced the increase in enzyme activities. Tocotrienol on its own had no effect on the enzyme activities.
    Matched MeSH terms: Kidney/drug effects*
  18. Gupta G, Chellappan DK, Kikuchi IS, Pinto TJA, Pabreja K, Agrawal M, et al.
    PMID: 29199592 DOI: 10.1615/JEnvironPatholToxicolOncol.2017019457
    Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
    Matched MeSH terms: Kidney/drug effects*
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