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Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."
Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011
Dr. Shankar P.R.
"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."
Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011 Anuradha
Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.
Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020
Original article / research
Full Version
Effect of Hydroalcoholic Root Extract of Aerva lanata on Acetaminophen Induced Hepatotoxicity in Wistar Rats
Correspondence Address :
Dr. Nileshraj Govindaraj,
Flat F1, Sai Nivas, Sai Balaji Foundation, Nanmangalam, Chennai, Tamil Nadu, India.
E-mail: nileshgovindaraj@gmail.com
Introduction: Acute acetaminophen poisoning leads to fulminant hepatic failure and renal tubular damage. N-Acetyl Cysteine (NAC), an antidote for acetaminophen poisoning, carries its own adverse effect profile such as anaphylactoid reactions, cerebral oedema and hyponatremia at high doses. Aerva lanata, an erect or prostate herbaceous weed has a wide range of medicinal uses like, hepatoprotection, nephroprotection, antiasthamatic and antiamoebic. Previous study on rats have shown that hydroalcoholic root extract of Aerva lanata has significant hepatoprotective property when administered before acetaminophen.
Aim: To evaluate the effect of hydroalcoholic root extract of Aerva lanata and NAC, as monotherapy and in combination, for acetaminophen induced hepatotoxicity in albino Wistar rats.
Materials and Methods: This was an experimental animal study. Thirty adult male albino Wistar rats were equally divided into five groups: group I-vehicle, group II-acetaminophen only, group III-acetaminophen+NAC, group IV-acetaminophen+Aerva lanata root extract, group V-Acetaminophen+NAC+Aerva lanata root extract. Hepatotoxicity was induced in rats belonging to groups II, III, IV and V using acetaminophen (2 g/kg p.o). All rats were sacrificed after 72 hours of drug administration, blood samples were sent for biochemical analysis. Liver and kidney samples were sent for histopathological studies. Results were analysed using one-way ANOVA followed by post hoc Dunnett t-test.
Results: Root extract of Aerva lanata significantly reduces the liver enzyme markers Aspartate Transaminase (AST), Alanine Transaminase (ALT), Gamma Glutamyl Transferase (GGT) and bilirubin) and blood urea concentration. The combination therapy (root extract with NAC) showed a highly significant decrease in AST, ALT, GGT (p<0.001), bilirubin (p<0.01) and blood urea (p<0.001) when compared with the paracetamol group. A significant reversal of liver injury was seen in histopathological studies.
Conclusion: The combination therapy showed better improvement of liver enzyme and renal parameters, along with significant improvement in histopathological changes. Hence, combination of hydroalcoholic root extract of Aerva lanata along with NAC can be effective in treating acetaminophen poisoning.
Antidote, Herbal root extract, Liver damage, Paracetamol
Drug induced hepatotoxicity leads to significant elevation of ALT more than three times the Upper Limit of Normal (ULN). The prevalence of drug induced liver injury is estimated to be 5% of all hospital admissions and 50% of all acute liver failures (1). Elevated aminotransferases along with jaundice is associated with increased mortality and need for liver transplant (2).
Acetaminophen (Paracetamol), a Nonsteroidal Anti-Inflammatory Drug (NSAID), is often used in clinical practice as an antipyretic and an analgesic (3). Easy availability of acetaminophen over the counter increases the risk of acute acetaminophen poisoning in both adults and children due to overdosage. The hepatic glucuronide conjugating ability is low in children. Even though the toxic dose of acetaminophen is > 10 g in adult, it is less in children (4). N-Acetyl-P-Benzoquinone Imine (NAPQI), a toxic intermediate metabolite formed during the metabolism of acetaminophen is the substance responsible for hepatotoxicity (5).
N-acetyl Cysteine (NAC) is the traditional drug used for the treatment of acetaminophen poisoning. NAC helps in providing cysteine for glutathione synthesis and also forms an adduct with NAPQI directly. But it has adverse effects which include unpleasant taste, vomiting, anaphylactoid reactions and at high doses it might even cause cerebral oedema and hyponatremia (6).
Aerva lanata is an erect or prostate herbaceous weed belonging to the family Amaranthaceae. The leaves are obovate or sub-opticular with greenish white flowers. Aerva lanata has a wide variety of medicinal uses, namely antimicrobial, antiamoebic, nephroprotective, antiasthamatic, hypolipidemic, hepatoprotective (7).
Previous studies on rats show that root extract of the plant Aerva lanata have hepatoprotective activity when administered before acetaminophen as a prophylaxis (8). But the implication of the plant as treatment for paracetamol poisoning and its possible synergism with NAC remains unexplored.
This study aimed to find out the effect of hydroalcoholic root extract of Aerva lanata when given orally, alone and in combination with NAC in treatment (instead of prophylaxis) of hepatotoxicity induced by acetaminophen in male albino Wistar rats and to assess its renoprotective effect.
This was an experimental animal study and 30 adult male albino Wistar rats were selected for the experiment. Rats were divided randomly into five groups. Each group contained six rats. This study was conducted for a period of four weeks (August 2014) in Sri Manakula Vinayagar Medical College and Hospital, Puducherry. Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines were adhered and Institutional Animal Ethics Committee clearance (SMVMCH- IAEC 1524/10/2013) was obtained before the research.
Inclusion criteria: Albino Wistar rats, male or female, age more than 12 weeks were included in this study.
Exclusion criteria: Animals with co-morbidities and knock-out animals were excluded in this study.
Study Procedure
Root of Aerva lanata plant was collected from Tiruchirappalli district, Tamil Nadu, India. Freshly collected plant materials were washed under running tap water and distilled water to remove adhering dust, then dried under shade and mechanically reduced to moderate coarse powder. The coarse powder was defatted with petroleum ether and then extracted with 80% ethanol using soxhlet apparatus. The extract was then concentrated using a rotary evaporator at 40ºC under reduced pressure. The concentrated extract was then transferred to a china dish and heated in a thermostat-controlled water bath until it was completely dry. Rats were grouped as follows and given their respective treatments (Table/Fig 1).
Doses were selected on the basis of previous studies (8),(9),(10),(11). Distilled water was used as a vehicle. After 24 hours of the last dose of drug (i.e., 72 hours from the first dose) all the animals were anaesthetised using ether and 2 mL of blood samples from each animal from all groups were taken from retro orbital venous plexus of eye using capillary tubes. All animals were sacrificed using high dose of pentobarbitone. For histopathological study, a portion of liver and kidney tissue was separated and placed in a neutral buffered formalin for fixation. After regular processing, tissues were embedded in paraffin wax, and then sectioned (4-5 μm) using a microtome. Sections were stained using Haematoxylin and Eosin (H&E). Histopathological changes in tissue morphology were noted.
Statistical Analysis
Statistical Package for the Social Sciences (SPSS) software version 16.0 was used. Data were analysed by one-way analysis of variance (ANOVA) and results were expressed as mean±Standard Deviation (SD). Significance of difference between groups was further analysed with Dunnett’s (2-sided) test for post hoc comparisons. The p-value of <0.05 was considered statistically significant.
1. Effect on AST, ALT and GGT levels
Vehicle treated animals (group I) showed that the AST and ALT levels were maintained at a mean value of 164.16±11.39 and 78±9.25, respectively. Acetaminophen administration (group II) resulted in a significant increase (p<0.001) in both AST and ALT levels when compared with vehicle treated group (group I). Group III animals administered with NAC monotherapy showed a significant decrease (p<0.01) in AST and ALT levels compared with acetaminophen group (group II). Aerva lanata root extract monotherapy (group IV) also showed a significant decrease in AST and ALT levels (p<0.05) on comparison with acetaminophen group (group II), whereas combination therapy (group V) of Aerva lanata root extract and NAC showed a highly significant decrease of AST level when compared with acetaminophen (p<0.001), NAC (p<0.01) and Aerva lanata root extract (p<0.001) treated animals. ALT level of animals belonged to combination therapy group also showed a significant reduction (p<0.001) on comparison with acetaminophen group animals (group II) as illustrated in (Table/Fig 2).
The GGT values of vehicle treated animals (group I) showed a mean value of 5.21±0.53. This value was raised significantly (p<0.001) on administration of acetaminophen (group II). Aerva lanata root extract and NAC combination therapy showed a highly significant reduction of GGT values (p<0.001) on comparison with acetaminophen group. Combination therapy also showed a significant reduction of GGT values when compared with NAC monotherapy (p<0.01) and Aerva lanata root extract monotherapy (p<0.05) treated groups as depicted in (Table/Fig 2).
2. Effect on bilirubin levels
Bilirubin (mean) levels of vehicle treated rats (group I) were 0.66±0.08 (Total bilirubin) and 0.21±0.04 (direct bilirubin). When acetaminophen was administered (group II), significant increase in both total bilirubin (p<0.01) and direct bilirubin (p<0.001) were seen on comparison with vehicle treated animals (group I). Treatment with NAC per se (group III) showed a significant decrease (p<0.05) of both total and direct bilirubin levels when compared with acetaminophen group animals. Similar reduction of bilirubin levels (p<0.05) was seen in the group which received Aerva lanata root extract monotherapy (group IV). However, group V animals who received combination therapy of Aerva lanata root extract and NAC showed a highly significant reduction of both total and direct bilirubin levels (p<0.01) when compared with acetaminophen group animals as depicted in (Table/Fig 3).
3. Effect on renal parameters
Blood urea concentration and serum creatinine values of vehicle treated animals (group I) were maintained at mean values of 19.88±0.91 and 0.33±0.08, respectively. A marked increase (p<0.001) in blood urea concentration was seen after administration of acetaminophen (group II) when compared with vehicle treated animals (group I). In the group treated with NAC alone (group III), no significant alterations in blood urea and serum creatinine levels were seen when compared with the untreated acetaminophen group animals. (group II) Aerva lanata root extract monotherapy group animals (group IV) showed a highly significant decrease in blood urea concentration compared with acetaminophen (p<0.001) and NAC (p<0.01) treated groups. Combination therapy of Aerva lanata root extract and NAC also showed a highly significant reduction of blood urea levels on comparison with acetaminophen (p<0.001), NAC monotherapy (p<0.001) and Aerva lanata root extract monotherapy (p<0.05) treated groups as shown in (Table/Fig 4).
No significant changes in creatinine values were observed in any of the treatment groups.
4. Histopathological examination of liver and kidney
Histological profile of group I animals treated with distilled water (vehicle treated) shows normal hepatic architecture with radially placed hepatic cells, large spherical nucleus and granular cytoplasm. Areas around portal triad and Central Vein (CV) showed no apparent injury. The (Table/Fig 5)a Liver sections of group II animals who received acetaminophen alone showed extensive fatty changes, cloudy swelling, parenchymal haemorrhage, Periportal Inflammation (PPI), vascular dilatation and congestion (Table/Fig 6)a. Group III animals treated with NAC showed mild cloudy swelling and focal mild fatty changes (Table/Fig 7)a. Aerva lanata root extract monotherapy (group IV) showed normal hepatocytes with vascular congestion and dilatation. Occasional mild cloudy swelling is seen (Table/Fig 8)a. Combination therapy of Aerva lanata root extract and NAC in group V showed normal hepatic architecture with mild vessel dilatation and focal mild cloudy swelling (Table/Fig 9)a. Histopathological examinations of sections of kidney tissue from group I (Vehicle) which received distilled water showed normal architecture with glomeruli and tubules (Table/Fig 5)b. Kidney sections of group II animals showed congested blood vessels as shown in (Table/Fig 6)b. Group III, IV, V showed normal architecture of kidney (Table/Fig 7)b, (Table/Fig 8), (Table/Fig 9)b.
The traditional drug NAC used as an antidote for acetaminophen poisoning is associated with increased risk of adverse drug reactions like anaphylactoid reaction, etc. There is an a need of a drug with lesser adverse reactions. This study evaluated the effect of hydroalcoholic root extract of Aerva lanata in treating acetaminophen induced hepatotoxicity in experimental albino Wistar rats.
1. Liver parameters
(i) AST and ALT: In this study, acetaminophen group showed a significant increase in AST and ALT levels when compared with vehicle treated group (p<0.001). Treatment with NAC alone reduces the AST and ALT levels (p<0.01) on comparison with acetaminophen group, which was similar to the study conducted by Kamalakannan N et al., demonstrating NAC significantly reduced the AST levels of Wistar rats (12). The present study suggested that Aerva lanata root extract monotherapy significantly decreased the AST and ALT levels (p<0.05) compared to acetaminophen treated group. Reduction in aminotransferase levels was similar to another study (13) which showed that Aerva lanata root extract monotherapy significantly decreased AST and ALT levels when compared with acetaminophen treated animals.
Moreover, the combination of Aerva lanata root extract and NAC showed a significant reduction of the AST and ALT levels compared to acetaminophen group (p<0.001) and also showed a highly significant decrease in AST level (p<0.01) compared to Aerva lanata monotherapy and NAC monotherapy groups. This profound decrease in aminotransferase levels could be due to the additive effect of these two drugs (Aerva lanata root extract and NAC) when given together.
(ii) GGT: Increase in GGT value was seen in acetaminophen treated group in comparison with vehicle treated group (p<0.001). NAC reduced the GGT values when given alone (p<0.01) on comparison with acetaminophen group which is on par with the study conducted by Kamalakannan N et al., (12). Present study showed that monotherapy with Aerva lanata root extract significantly reduced the GGT levels when compared with animals which received acetaminophen alone (p<0.05). Our study results were also identical to Rajkapoor B et al., which includes a significant decrease in GGT level by Phyllanthus polyphyllus leaf extract monotherapy when compared with acetaminophen treated group (14). Furthermore present study also showed that Aerva lanata root extract when given in combination with NAC reduced the GGT levels in a highly significant manner on comparison with both acetaminophen group (p<0.001) and NAC monotherapy group animals (p<0.05)
(iii) Bilirubin: Administration of acetaminophen showed a significant increase of total (p<0.01) and direct bilirubin (p<0.001) levels when compared with animals in the vehicle treated group which is similar to the study conducted by Ramana Rao R et al., Iyanda AA and Adeniyi FAA and Soni RK et al., (15),(16),(17). NAC and Aerva lanata root extract monotherapy showed a reduction of both total and direct bilirubin (p<0.05) in a similar fashion, whereas highly significant decrease in bilirubin levels were observed in the group which received combination of Aerva lanata root extract and NAC when compared with acetaminophen treated group (p<0.01). This is also identical to the results of Manokaran S et al., which produced a significant reduction of bilirubin levels (8). No significant difference in bilirubin levels was observed on comparison with NAC or root extract monotherapy. This combination therapy showed a favourable decrease in liver parameters namely AST, ALT, GGT, bilirubin levels which could be due to possible synergistic action among the two drugs.
2. Renal Parameters
Significant elevation of blood urea in acetaminophen group animals (p<0.001) on comparison with vehicle treated group is identical to the study conducted by Pathan MM et al., (18). In present study, administration of NAC alone showed no decrease in blood urea when compared with acetaminophen group. The present study showed that Aerva lanata root extract when given alone or in combination with NAC produced a highly significant reduction (p<0.001) in blood urea level on comparison with acetaminophen group. This result is in conjunction with the study conducted by Barkavi R and Venkatalakshmi P who demonstrated decrease in both urea and creatinine levels (19). Similar reduction in blood urea concentration was also seen when compared with NAC monotherapy (p<0.001) group animals. However, no significant changes in creatinine levels were observed in any treatment groups of the current study.
3. Histopathological studies
In the current study, animals in the vehicle treated group showed a normal histological liver profile. The sections of livers of animals belonged to acetaminophen group (group II) showed cloudy swelling, fatty changes, parenchymal haemorrhage, PPI, vascular dilatation and congestion which is at par with the study conducted by Kanchana N and Sadiq M (20). Histopathological liver profiles of animals belonged to both Aerva lanata root extract monotherapy and in combination with NAC showed a significant improvement over the animals of acetaminophen group. It is also evident from the results that the combination therapy produced significant reversal of the hepatotoxicity induced by acetaminophen, with normal hepatic architecture and occasional focal mild cloudy swelling.
Even though, many studies have been done on NAC in treating hepatotoxicity induced by acetaminophen, only a few have been conducted on hepatoprotective effect of Aerva lanata root extract. No study has been conducted by combining NAC and Aerva lanata root extract in exploring their synergistic effect in animal models. Standard animal model for hepatotoxicity was used in this study. Liver and renal parameters along with histopathological examination were also monitored in this study and showed that the combination therapy has significant effect in treating hepatotoxicity induced by acetaminophen along with renoprotective property.
Limitation(s)
This study carries its own limitations like the phytochemical analysis for hydroalcoholic root extract of Aerva lanata was not done and the total protein and serum albumin values were not included. The effects of this extract on gluconeogenesis of liver was not studied, and toxicity studies for this extract needs to be explored.
It is to conclude that the hydroalcoholic root extract of Aerva lanata has a significant effect in treatment of hepatotoxicity induced by acetaminophen. However, combination therapy is a better treatment regimen compared with the monotherapy of NAC or Aerva lanata root extract. It has additional hepatoprotective and renoprotective effects. Hence, combination of hydroalcoholic root extract of Aerva lanata along with NAC can be effective in treating acetaminophen poisoning. It is worthwhile to consider this aspect for further clinical trials and application in patients with acetaminophen over dosage.
10.7860/JCDR/2021/49837.15351
Date of Submission: Apr 09, 2021
Date of Peer Review: May 13, 2021
Date of Acceptance: Jul 01, 2021
Date of Publishing: Sep 01, 2021
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA
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