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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.
Scientific research related to calcium channel blockers poisoning: Bibliometric analysis in Scopus, 1968-2012

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

Hum Exp Toxicol, 2015 Nov;34(11):1162-70.
PMID: 25673180 DOI: 10.1177/0960327115571768

PURPOSE: Calcium channel blockers (CCBs) were the most common agents associated with a significant morbidity and mortality rate. The main objective of this study was to examine the publication pattern related to CCBs poisoning at the global level using bibliometric analysis of articles published in SciVerse Scopus online database.
METHODS: Data were searched for documents that contained specific words regarding CCB poisoning as keywords in the title. No time period limitations were specified in the search regarding the starting year. The ending date of the search was 31 December 2012.
RESULTS: The criteria were met by 713 publications from 53 countries. The largest number of articles associated with CCBs was from the United States (30%), followed by the United Kingdom (7.4%), Japan (6%), and Germany (5.6%). No data related to CCBs were published from 159 (75%) of 212 countries registered in World Bank online database. There was no correlation between the number of published articles in the country and its population size (r = 0.03, p > 0.926). United Kingdom and Australia were the leading countries in terms of number of CCBs publications per million inhabitants (0.83 and 0.82 articles per million inhabitants, respectively), followed by the United States (0.68). Countries with a large population, such as India, tended to rank relatively low (0.01 articles per million inhabitants). The total number of citations at the time of data analysis (23 October 2014) was 6462, with an average of 9.1 citations per document. The highest median (interquartile range) number of citations was 8 (8-18) for the United States, followed by 6 (1-21) for Australia, 5 (1-15) for the United Kingdom, and 5 (1-24) for Canada. The h-index of the retrieved documents was 37.
CONCLUSIONS: Scientific production on CCBs poisoning is increasing; nonetheless, the international collaboration is still rare. The amount of CCBs-based research activity was low or not available in most countries. More regional epidemiological studies are required to bridge the gap in CCBs-based research and to promote better evaluation of CCBs poisoning worldwide.
KEYWORDS: Bibliometric; Scopus; calcium channel blockers; citations; drug overdose; poisoning; toxicity
Worldwide research productivity of paracetamol (acetaminophen) poisoning: a bibliometric analysis (2003-2012)

Zyoud SH, Al-Jabi SW, Sweileh WM

Hum Exp Toxicol, 2015 Jan;34(1):12-23.
PMID: 24758786 DOI: 10.1177/0960327114531993

PURPOSE: There is a lack of data concerning the evaluation of scientific research productivity in paracetamol poisoning from the world. The purposes of this study were to analyse the worldwide research output related to paracetamol poisoning and to examine the authorship pattern and the citations retrieved from the Scopus database for over a decade.
METHODS: Data were searched for documents with specific words regarding paracetamol poisoning as 'keywords' in the title or/and abstract. 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 (GDP) per capita.
RESULTS: There were 1721 publications that met the criteria during study period from the world. All retrieved documents were published from 72 countries. The largest number of articles related to paracetamol poisoning was from the United States (US; 30.39%), followed by India (10.75%) and the United Kingdom (UK; 9.36%). The total number of citations at the time of data analysis was 21,109, with an average of 12.3 citations per each documents and median (interquartile range) of 4 (1-14). The h-index of the retrieved documents was 57. After adjusting for economy and population power, India (124.2), Nigeria (18.6) and the US (10.5) had the highest research productivity. Countries with large economies, such as the UK, Australia, Japan, China and France, tended to rank relatively low after adjustment for GDP over the entire study period.
CONCLUSION: Our study demonstrates evidence that research productivity related to paracetamol poisoning has increased rapidly during the recent years. The US obviously dominated in research productivity. However, certain smaller country such as Nigeria has high scientific output relative to their population size and GDP. A highly noticeable increase in the contributions of Asia-Pacific and Middle East regions to scientific literature related to paracetamol poisoning was also observed.
KEYWORDS: Bibliometric; Scopus; acetaminophen; citations; paracetamol; poisoning
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.
High prevalence of hypokalemia after acute acetaminophen overdose: impact of psychiatric illness

Zyoud SH, Awang R, Syed Sulaiman SA, Al-jabi SW

Hum Exp Toxicol, 2010 Sep;29(9):773-8.
PMID: 20144962 DOI: 10.1177/0960327110361759

Hypokalemia is not an isolated disease but an associated finding in a number of different diseases. It is also a commonly neglected condition among patients with acute acetaminophen overdose.
Incidence of adverse drug reactions induced by N-acetylcysteine in patients with acetaminophen overdose

Zyoud SH, Awang R, Syed Sulaiman SA, Sweileh WM, Al-Jabi SW

Hum Exp Toxicol, 2010 Mar;29(3):153-60.
PMID: 20071472 DOI: 10.1177/0960327109359642

Intravenous N-acetylcysteine (IV-NAC) is widely recognized as the antidote of choice for acetaminophen overdose. However, its use is not without adverse drug reactions (ADR) that might affect therapeutic outcome or lead to treatment delay.
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
Fulltext Kaempferol ameliorates palmitate-induced lipid accumulation in HepG2 cells through activation of the Nrf2 signaling pathway

Zhao L, Yang L, Ahmad K

Hum Exp Toxicol, 2023;42:9603271221146780.
PMID: 36607234 DOI: 10.1177/09603271221146780

OBJECTIVES: Kaempferol (KMF), has beneficial effects against hepatic lipid accumulation. In this study, we aimed to investigate molecular mechanism underlying the protective effect of KMF on lipid accumulation.
METHODS: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24 h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.
RESULTS: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).
CONCLUSION: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.
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.
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.
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.
Itraconazole- and fluconazole-induced toxicity in rat hepatocytes: a comparative in vitro study

Somchit N, Hassim SM, Samsudin SH

Hum Exp Toxicol, 2002 Jan;21(1):43-8.
PMID: 12046723

This current study was to investigate the in vitro cytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose- and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.
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.
Tocotrienol preserves ovarian function in cyclophosphamide therapy

Saleh HS, Omar E, Froemming GR, Said RM

Hum Exp Toxicol, 2015 Oct;34(10):946-52.
PMID: 25585998 DOI: 10.1177/0960327114564793

Cyclophosphamide (CPA) chemotherapy leads to ovarian failure and infertility. Tocotrienol (T3) is an antioxidant and anti-inflammatory agent. The role of T3 in ovarian protection throughout chemotherapy remains unclear.
Profile of poisoning admissions in Malaysia

Rajasuriar R, Awang R, Hashim SB, Rahmat HR

Hum Exp Toxicol, 2007 Feb;26(2):73-81.
PMID: 17370864

We retrospectively reviewed poisoning admissions to all government health facilities from 1999 to 2001, in an effort to expand our current knowledge on poisoning in Malaysia to a level that better reflects a nationwide burden. There were 21 714 admissions reported with 779 deaths. The case-fatality rate was 35.88/1000 admissions. The majority of admissions (89.7%) and deaths (98.9%) occurred in adults. Some 55.1% of all admissions were female, mostly involving pharmaceutical agents. Male poisoning admissions were more often due to chemical substances. The prevalence of poisoning and death was highest among Indians compared to all other races in Malaysia. Overall, the majority of poisoning admissions were due to pharmaceutical agents, with agents classified as non-opioid analgesics, anti-pyretics and anti-rheumatics the most common. Pesticides accounted for the largest number of fatalities. It was also the commonest substance reported in cases of intentional self-harm. Most cases of poisoning admissions occurred due to accidental exposure (47%), followed by cases of intentional self-harm (20.7%). Overall, this study has managed to contribute substantial additional information regarding the epidemiology of poisoning in Malaysia, highlighting important issues, such as the rampant poisonings involving pesticides and analgesics, as well as the high prevalence of poisoning among Indians in Malaysia.
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.
Insight into potential mechanisms of hypobaric hypoxia-induced learning and memory deficit - Lessons from rat studies

Qaid E, Zakaria R, Sulaiman SF, Yusof NM, Shafin N, Othman Z, et al.

Hum Exp Toxicol, 2017 Dec;36(12):1315-1325.
PMID: 28111974 DOI: 10.1177/0960327116689714

Impairment of memory is one of the most frequently reported symptoms during sudden hypoxia exposure in human. Cortical atrophy has been linked to the impaired memory function and is suggested to occur with chronic high-altitude exposure. However, the precise molecular mechanism(s) of hypoxia-induced memory impairment remains an enigma. In this work, we review hypoxia-induced learning and memory deficit in human and rat studies. Based on data from rat studies using different protocols of continuous hypoxia, we try to elicit potential mechanisms of hypobaric hypoxia-induced memory deficit.
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.
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.
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.

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