MyMedR

Displaying publications 1 - 20 of 31 in total

Abstract:

Sort:

Fulltext A bibliometric analysis of research productivity of Malaysian publications in leading toxicology journals during a 10-year period (2003-2012)

Zyoud Sh, Al-Jabi S, Sweileh W, Awang R

Hum Exp Toxicol, 2014 Dec;33(12):1284-93.
PMID: 24505047 DOI: 10.1177/0960327113514101

Toxicology in Malaysia has experienced rapid development and made great progress in education and research in conjunction with economic development in Malaysia over the past two decades.
A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats

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.
Amelioration of ferric nitrilotriacetate-induced hepatotoxicity in Wistar rats by diallylsulfide

Ansar S, Iqbal M

Hum Exp Toxicol, 2016 Mar;35(3):259-66.
PMID: 25904316 DOI: 10.1177/0960327115583362

Garlic contains diallylsulfide (DAS) and other structurally related compounds that are widely believed to be active agents in preventing cancer. This study shows the effect of DAS (a phenolic antioxidant used in foods, cosmetics, and pharmaceutical products) on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats. Male albino rats of Wistar strain weighing 125-150 g were given a single dose of Fe-NTA (9 mg kg(-1) body weight, intraperitoneally) after 1 week of treatment with 100 and 200 mg kg(-1) DAS in corn oil respectively administered through the gavage. Fe-NTA administration led to 2.5-fold increase in the values of both alanine transaminase and aspartate aminotransferase, respectively, and 3.2-fold increase in the activity of lactate dehydrogenase, microsomal lipid peroxidation to approximately 2.0-fold compared to saline-treated control. The activities of glutathione (GSH) and other antioxidant enzymes decreased to a range of 2.2-2.5-fold. These changes were reversed significantly (p < 0.001) in animals receiving a pretreatment of DAS. DAS protected against hepatic lipid peroxidation, hydrogen peroxide generation, preserved GSH levels, and GSH metabolizing enzymes to 60-80% as compared to Fe-NTA alone-treated group. Present data suggest that DAS can ameliorate the toxic effects of Fe-NTA and suppress oxidant-induced tissue injury and hepatotoxicity in rats.
An analysis of the length of hospital stay after acetaminophen overdose

Zyoud SH, Awang R, Sulaiman SA, Al-Jabi SW

Hum Exp Toxicol, 2011 Jul;30(7):550-9.
PMID: 20630911 DOI: 10.1177/0960327110377647

Acetaminophen is one of the most commonly encountered medications in self-poisoning, with a high rate of morbidity. The prevalence and characteristics of acetaminophen intoxication associated with long hospital stay in patients are not well defined.
Analysis of lead content in herbal preparations in Malaysia

Ang HH, Lee EL, Matsumoto K

Hum Exp Toxicol, 2003 Aug;22(8):445-51.
PMID: 12948085 DOI: 10.1191/0960327103ht382oa

In Malaysia, the phase 3 registration for traditional medicines was implemented on 1 January 1992 under the Control of Drugs and Cosmetics Regulation 1984, emphasizing quality, efficacy and safety (including the detection of the presence of heavy metals) in all pharmaceutical dosage forms of traditional medicine preparations. Therefore, a total of 100 products in various pharmaceutical dosage forms of a herbal preparation, were analysed for lead content using atomic absorption spectrophotometer. Results showed that 8% (eight products) possessed 10.64-20.72 ppm of lead, and therefore, do not comply with the quality requirement for traditional medicines in Malaysia. One of these products, M-Tongkat Ali (exhibited 10.64 +/-0.37 ppm of lead), was in fact already registered with the DCA Malaysia. The rest, Sukarno Tongkat Ali, Eurycoma Madu, Super Pill Tongkat Ali, Force Pill Tongkat Ali, Tender Pill Tongkat Ali, Super Pill Tongkat Ali Plus and Great Pill Tongkat Ali Plus have not registered with the DCA Malaysia and exhibited 12.24-20.72 ppm of lead. Although this study showed that only 92% of the products complied with the quality requirement for traditional medicines in Malaysia, however, they cannot be assumed safe from lead contamination because of batch-to-batch inconsistency.
Antioxidant and nephroprotective potential of butylated hydroxyanisole against ferric nitrilotriacetate-induced oxidative stress and early tumor events

Ansar S, Iqbal M

Hum Exp Toxicol, 2016 Apr;35(4):448-53.
PMID: 26078281 DOI: 10.1177/0960327115591378

The present study was aimed to study protective effect of butylated hydroxyanisole (BHA), a phenolic antioxidant used in foods on ferric nitrilotriacetate (Fe-NTA)-induced nephrotoxicity. Male albino rats of Wistar strain (4-6 weeks old) weighing 125-150 g were used in this study. Animals were given a single dose of Fe-NTA (9 mg kg(-1) body weight) after treatment with BHA (1 and 2 mg animal(-1) day(-1)). Fe-NTA treatment enhanced ornithine decarboxylase (ODC) activity to 5.3-fold, and [(3)H]-thymidine incorporation in DNA to 2.5-fold in kidney compared with the corresponding saline-treated control, whereas glutathione (GSH) levels and the activities of antioxidant enzymes decreased to a range of 2- to 2.5-fold in kidney. These changes were reversed significantly in animals receiving a pretreatment of BHA. The enhanced ODC activity and DNA synthesis showed a reduction to 2.12-fold and 1.15-fold, respectively, at a higher dose of 2 mg BHA day(-1) animal(-1), compared with the Fe-NTA-treated groups. Pretreatment with BHA prior to Fe-NTA treatment increased GSH and the activities of antioxidant enzymes to a range of 1.5- to 2-fold in kidney. The results indicate that BHA suppresses Fe-NTA-induced nephrotoxicity in male Wistar rats.
Antioxidant potential of Cymbopogon citratus extract: alleviation of carbon tetrachloride-induced hepatic oxidative stress and toxicity

Koh PH, Mokhtar RA, Iqbal M

Hum Exp Toxicol, 2012 Jan;31(1):81-91.
PMID: 21508074 DOI: 10.1177/0960327111407226

This study was aimed to evaluate the effect of Cymbopogon citratus against carbon tetrachloride (CCl(4))-mediated hepatic oxidative damage in rats. Rats were administrated with C. citratus extract (100, 200 and 300 mg/kg b.w.) for 14 days before the challenge of CCl(4) (1.2 ml/kg b.w. p.o) on 13th and 14th days. Hepatic damage was evaluated by employing serum biochemical parameters (alanine aminotransferase-ALT, aspartate aminotransferase-AST and lactate dehydrogenase-LDH), malondialdehye (MDA) level, reduced GSH and antioxidant enzymes (catalase: CAT, glutathione peroxidase: GPX, quinone reductase: QR, glutathione S-transferase: GST, glutathione reductase: GR, glucose-6-phosphate dehyrogenase: G6PD). In addition, CCl(4)-mediated hepatic damage was further evaluated by histopathological examination. However, most of these changes were alleviated by prophylactic treatment of animals with C. citratus dose dependently (p < 0.05). The protection was further evident through decreased histopathological alterations in liver. The results of the present study indicated that the hepatoprotective effect of C. citratus might be ascribable to its antioxidant and free radical scavenging property.
Coadministration of alloxan and nicotinamide in rats produces biochemical changes in blood and pathological alterations comparable to the changes in type II diabetes mellitus

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.
Cytochrome P450 4B1 (CYP4B1) as a target in cancer treatment

Lim S, Alshagga M, Ong CE, Chieng JY, Pan Y

Hum Exp Toxicol, 2020 Jun;39(6):785-796.
PMID: 32054340 DOI: 10.1177/0960327120905959

Cytochrome P450 4B1 (CYP4B1) plays crucial roles in biotransforming of xenobiotics. Its predominant extrahepatic expression has been associated with certain tissue-specific toxicities. However, the expressions of CYP4B1 in various cancers and hence their potential roles in cancer development were inclusive. In this work, existing knowledge on expression and regulation of CYP4B1 gene and protein, catalysis of CYP4B1, association of CYP4B1 with cancers, contradicting findings about human CYP4B1 activities as well as the employing CYP4B1 in suicide gene approach for cancer treatment were reviewed. To date, it appears that there is a wide spectrum of tissue distribution of CYP4B1 with lungs as the predominant sites. Several nuclear receptors are possibly responsible for regulating its gene expression. The involvement of CYP4B1 in cancer was considered via activation of procarcinogens and neovascularization. However, human CYP4B1 was found to be inactive due to a substitution of proline with serine at position 427. Suicide gene approach combining reengineered CYP4B1 and prodrug 4-ipomeanol (4-IPO) has shown a promising potential for targeted cancer therapy. Further studies should focus on the verification of human CYP4B1 catalytic activities. More compounds with similar structure as 4-IPO should be tested to identify more alternative agents for the suicide gene approach in cancer treatment.
Cytotoxic and antioxidant effects of methoxylated stilbene analogues on HepG2 hepatoma and Chang liver cells: Implications for structure activity relationship

Hasiah AH, Ghazali AR, Weber JF, Velu S, Thomas NF, Inayat Hussain SH

Hum Exp Toxicol, 2011 Feb;30(2):138-44.
PMID: 20385705 DOI: 10.1177/0960327110368739

Stilbenes possess a variety of biological activities including chemopreventive activity. This study was conducted to evaluate the structural activity relationships of six methoxylated stilbene analogues with respect to their cytotoxic effects and antioxidant activities on HepG2 hepatoma and Chang liver cells. The cytotoxic and total antioxidant activities of six stilbene analogues were determined by MTT and Ferric Reducing Antioxidant Power (FRAP) assays, respectively. We found that the cis-methoxylated stilbene: (Z)-3,4,4'-trimethoxystilbene was the most potent and selective antiproliferative agent (IC₅₀ 89 µM) in HepG2 cells. For the total antioxidant activity, compounds possessing hydroxyl groups at the 4' position namely (E)-3-methoxy-4'-hydroxystilbene, (E)-3,5-dimethoxy-4'-hydroxystilbene (pterostilbene), (E)-4-methoxy-4'-hydroxystilbene showed the highest antioxidant activity. Structure activity relationship studies of these compounds demonstrated that the cytotoxic effect and antioxidant activities of the tested compounds in this study were structurally dependent.
Decline in sperm count in European men during the past 50 years

Sengupta P, Borges E, Dutta S, Krajewska-Kulak E

Hum Exp Toxicol, 2018 Mar;37(3):247-255.
PMID: 28413887 DOI: 10.1177/0960327117703690

PURPOSE: To investigate whether the sperm concentration of European men is deteriorating over the past 50 years of time.
MATERIALS AND METHODS: We analysed the data published in English language articles in the past 50 years in altering sperm concentration in European men.
RESULTS: A time-dependent decline of sperm concentration ( r = -0.307, p = 0.02) in the last 50 years and an overall 32.5% decrease in mean sperm concentration was noted.
CONCLUSION: This comprehensive, evidence-based meta-analysis concisely presents the evidence of decreased sperm concentration in European male over the past 50 years to serve the scientific research zone related to male reproductive health.
Diallyl sulphide, a component of garlic, abrogates ferric nitrilotriacetate-induced oxidative stress and renal damage in rats

Ansar S, Iqbal M, AlJameil N

Hum Exp Toxicol, 2014 Dec;33(12):1209-16.
PMID: 24596035 DOI: 10.1177/0960327114524237

Ferric nitrilotriacetate (Fe-NTA) induces tissue necrosis as a result of lipid peroxidation (LPO) and oxidative damage that leads to high incidence of renal carcinomas. The present study was undertaken to evaluate the effect of diallyl sulphide (DAS) against Fe-NTA-induced nephrotoxicity. A total of 30 healthy male rats were randomly divided into 5 groups of 6 rats each: (1) control, (2) DAS (200 mg kg(-1)), (3) Fe-NTA (9 g Fe kg(-1)), (4) DAS (100 mg kg(-1)) + Fe-NTA (9 mg Fe kg(-1)) and (5) DAS (200 mg kg(-1)) + Fe-NTA (9 mg Fe kg(-1)). Fe-NTA + DAS-treated groups were given DAS for a period of 1 week before Fe-NTA administration. The intraperitoneal administration of Fe-NTA enhanced blood urea nitrogen and creatinine levels with reduction in levels of antioxidant enzymes. However, significant restoration of depleted renal glutathione and its dependent enzymes (glutathione reductase and glutathione-S-transferase) was observed in DAS pretreated groups. DAS also attenuated Fe-NTA-induced increase in LPO, hydrogen peroxide generation and protein carbonyl formation (p < 0.05). The results indicate that DAS may be beneficial in ameliorating the Fe-NTA-induced renal oxidative damage in rats.
Drug and chemical poisoning admissions at a teaching hospital in Malaysia

Ab Rahman AF

Hum Exp Toxicol, 2002 Jul;21(7):377-81.
PMID: 12269700

A retrospective review of medical records was carried out to determine the pattern of drug and chemical poisoning cases admitted to a teaching hospital in Malaysia. Medical records of patients admitted during the period January 1987 to December 1995 were reviewed. They accounted for 0.2% of total admissions during the period. While all ages were represented, there was predominance of children, which showed little change throughout the nine-year period. Of all cases of poisoning, 77.8% were unintentional, 12.6% intentional and 9.6% were undetermined. Kerosene, pesticides and medicinal substances remained the common agents associated with poisoning. A significant number of patients sought treatment elsewhere before being admitted to the hospital. Of those who came directly to the hospital, many were presented late in the course of their poisoning. Only seven patients died and none were children. This study supports the need for greater emphasis on prevention of poisoning in children and among farmers in the state.
Evaluate the impact of hospital types on the availability of antidotes for the management of acute toxic exposures and poisonings in Malaysia

Al-Sohaim SI, Awang R, Zyoud SH, Rashid SM, Hashim S

Hum Exp Toxicol, 2012 Mar;31(3):274-81.
PMID: 21478291 DOI: 10.1177/0960327111405861

The availability of antidotes may be considered essential and lifesaving in the management of certain poisonings. Surveys carried out in a number of countries have demonstrated inadequate availability of a variety of poisoning antidotes.
Factors associated with adult poisoning in northern Malaysia: a case-control study

Fathelrahman AI, Ab Rahman AF, Zain ZM, Tengku MA

Hum Exp Toxicol, 2006 Apr;25(4):167-73.
PMID: 16696291

Data on adult risk factors associated with drug or chemical poisonings in Malaysia are scarce. The objective of the study was to identify possible risk factors associated with adult admissions to the Penang General Hospital (PGH) due to chemical poisoning and/or drug overdose. The present study was a case-control study, conducted over 18 weeks. One hundred acutely poisoned adult patients admitted to PGH during the period from September 2003 to February 2004 were considered as cases. Two hundred patients admitted to the same medical wards for other illnesses, during the same period, were matched for age and gender with the poisoned cases and thus selected as controls. McNemar test and binary logistic were used for univariate analysis and logistic regression analysis for multivariate analyses. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated for each predictor variable. Positive histories of psychiatric illness and previous poisoning, problems in boy/girl friend relationships, family problems, marital problems, Indian ethnicity, Chinese ethnicity, living in rented houses and living in a household with less than five people were significant risk factors associated with adult admissions due to poisoning.
Genetic, epigenetic, and lineage-directed mechanisms in benzene-induced malignancies and hematotoxicity targeting hematopoietic stem cells niche

Dewi R, Hamid ZA, Rajab NF, Shuib S, Razak SA

Hum Exp Toxicol, 2020 May;39(5):577-595.
PMID: 31884827 DOI: 10.1177/0960327119895570

Benzene is a known hematotoxic and leukemogenic agent with hematopoietic stem cells (HSCs) niche being the potential target. Occupational and environmental exposure to benzene has been linked to the incidences of hematological disorders and malignancies. Previous studies have shown that benzene may act via multiple modes of action targeting HSCs niche, which include induction of chromosomal and micro RNA aberrations, leading to genetic and epigenetic modification of stem cells and probable carcinogenesis. However, understanding the mechanism linking benzene to the HSCs niche dysregulation is challenging due to complexity of its microenvironment. The niche is known to comprise of cell populations accounted for HSCs and their committed progenitors of lymphoid, erythroid, and myeloid lineages. Thus, it is fundamental to address novel approaches via lineage-directed strategy to elucidate precise mechanism involved in benzene-induced toxicity targeting HSCs and progenitors of different lineages. Here, we review the key genetic and epigenetic factors that mediate hematotoxicological effects by benzene and its metabolites in targeting HSCs niche. Overall, the use of combined genetic, epigenetic, and lineage-directed strategies targeting the HSCs niche is fundamental to uncover the key mechanisms in benzene-induced hematological disorders and malignancies.
Global research productivity of N-acetylcysteine use in paracetamol overdose: A bibliometric analysis (1976-2012)

Zyoud SH, Al-Jabi SW, Sweileh WM, Awang R, Waring WS

Hum Exp Toxicol, 2015 Oct;34(10):1006-16.
PMID: 26429951 DOI: 10.1177/0960327114565494

PURPOSE: The main objective of this study was to examine the publication pattern of N-acetylcysteine (NAC) research output for paracetamol overdose at the global level.
METHODS: Data were searched for documents that contained specific words regarding NAC and paracetamol as keywords in the title and/or abstract and/or keywords. Scientific output was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product per capita.
RESULTS: The criteria were met by 367 publications from 33 countries. The highest number of articles associated with the use of NAC in paracetamol overdose was from the United States of America (USA; 39.78%), followed by the United Kingdom (UK; 11.99%). After adjusting for economy and population power, USA (2.822), Iran (1.784) and UK (1.125) had the highest research productivity. The total number of citations at the time of data analysis (14 March 2014) was 8785 with an average of 23.9 citations per document and a median (interquartile range) of 6 (1-22). The h-index of the retrieved documents was 48. The highest h-index was 32 for USA, followed by 20 for UK. Furthermore, the highest number of collaborations with international authors for each country was held by USA with 11 countries, followed by Canada with 7 countries.
CONCLUSION: The amount of NAC-based research activity was low in some countries, and more effort is needed to bridge this gap and to promote better evaluation of NAC use worldwide. Our findings demonstrate that NAC use for paracetamol overdose remains a hot issue in scientific research and may have a larger audience compared with other toxicological aspects. Editors and authors in the field of toxicology might usefully promote the submission of work on NAC in future to improve their journal's impact.
KEYWORDS: Bibliometric; NAC; Scopus; acetaminophen; acetylcysteine; citations; paracetamol; poisoning
Guggulsterone, a farnesoid X receptor antagonist lowers plasma trimethylamine-N-oxide levels: An evidence from in vitro and in vivo studies

Gautam A, Paudel YN, Abidin S, Bhandari U

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

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

Rahman A, Vasenwala SM, Iqbal M

Hum Exp Toxicol, 2017 Aug;36(8):785-794.
PMID: 27758841 DOI: 10.1177/0960327116665675

Glyceryl trinitrate (GTN) has been used widely as a potent vasodilator to treat heart conditions, such as angina pectoris and chronic heart failure. This study aims to elucidate the effect of exogenous nitric oxide (NO) administration, using GTN, on carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in rats. The results obtained demonstrated that NO generated by the administration of GTN affords protection against CCl4-induced oxidative stress and liver injury. Administration of CCl4resulted in a significant ( p < 0.001) increase in lipid peroxidation and tissue damage markers (aspartate and alanine transaminase and lactate dehydrogenase) release in serum. Parallel to these changes, CCl4also caused downregulation of antioxidant enzymes including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), and several fold induction in γ-glutamyl transpeptidase (GGT) activity. Subsequent administration of GTN resulted in significant ( p < 0.001) recovery of GSH-metabolizing enzymes in a dose-dependent manner. Further, administration of NO inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), exacerbated CCl4-induced oxidative tissue injury. Overall, the study suggests that GTN might suppress oxidant-induced tissue injury and hepatotoxicity in rats.
Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats: a comparative in vivo study

Somchit N, Norshahida AR, Hasiah AH, Zuraini A, Sulaiman MR, Noordin MM

Hum Exp Toxicol, 2004 Nov;23(11):519-25.
PMID: 15625777

Itraconazole and fluconazole are oral antifungal drugs, which have a wide spectrum antifungal activity and better efficacy than the older drugs. However, both drugs have been associated with hepatotoxicity in susceptible patients. The mechanism of antifungal drug-induced hepatotoxicity is largely unknown. Therefore, the aim of this present study was to investigate and compare the hepatotoxicity induced by these drugs in vivo. Rats were treated intraperitoneally with itraconazole or fluconazole either single (0, 10, 100 and 200 mg/kg) or subchronic (0, 10, 50 and 100 mg/kg per day for 14 days) doses. Plasma and liver samples were taken at the end of the study. A statistically significant and dose dependent increase of plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities were detected in the subchronic itraconazole-treated group. In addition, dose-dependent hepatocellular necrosis, degeneration of periacinar and mizonal hepatocytes, bile duct hyperplasia and biliary cirrhosis and giant cell granuloma were observed histologically in the same group. Interestingly, fluconazole treated rats had no significant increase in transaminases for both single and subchronic groups. In the subchronic fluconazole treated rats, only mild degenerative changes of centrilobular hepatocytes were observed. These results demonstrated that itraconazole was a more potent hepatotoxicant than fluconazole in vivo in rats.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links