Ethnobotanical Leaflets 12: 286-298. 2008.
Will Herbal-Paracetamol Combination Drug Prevent both Liver and Kidney Disease? - Results and Possibilities
Anjali Sharma, Mukesh Makwana and H.S. Rathore*
Cell Biology Unit, School of Studies in Zoology and Biotechnology
Vikram University, Ujjain 456010. India
*Contact: [email protected]
Issued 24 May 2008
An attempt has been made to briefly review the existing information on herbal compounds which could combat acetaminophen (paracetamol) toxicity. A careful perusal of literature revealed that acetaminophen overdose not only damages liver but also the kidney. Nevertheless, the kidney was badly ignored in studies aimed at preventing paracetamol toxicity with herbal drugs. On account of such major neglect, so far no herbal-paracetamol combination could be made. Milk thistly is only well researched drug which appears as a suitable future candidate, but its action towards the kidney must be studied. The importance of such studies in the future is discussed.
Key words: Acetaminophen/paracetamol, hepatoxicity, Nephrotoxicity, Herbal Drugs/combination.
Acetaminophen (Paracetamol: N-acetyl-p-aminophen) is an effective analgesic - antipyretic drug which is often used to treat pain and fever. Acetaminophen is available without prescription in many parts of the world (Goodman and Gilman 1996).
The most serious adverse effect of acute overdose of acetaminophen is dose-dependent, potentially fatal hepatic necrosis (Thomas 1993) which may be associated with renal tubular necrosis (Goodman and Gilman 1996). The number of self poisoning suicides with acetaminophen has grown alarming in recent years (Goodman and Gilman 1996; Gyamlani and Parikh 2002). According to a study in USA paracetamol was found to be associated with more than 10, 00, 00 cases of poisoning, 56000 visits to emergency departments, 26000 hospitalization and 450 deaths a year (BMJ 2002). Also acetaminophen was the drug most commonly taken in United Kingdom (Howton et al 1997) causing substantial number of deaths (Bray 1993). Cases of overdoses of acetaminophen in India are also not uncommon (Sharka et al. 1999).
The principal antidotal treatment is the administration of sulphydryl compound like N-acetyl-cysteine which act by replenishing hepatic stores of glutathione. This drug is effective only if given orally or intravenously within less than 10 hours after ingestion (Smilkstein et al 1988).
BRIEF REVIEW OF EXISTING REPORTS
In the past, several herbal compounds have also been screened to test their ability to reduce and / or nullify acetaminophen induced hepatotoxicity. These reports are given subsequently. It is of interest to mention here that only in two studies both liver and kidney were taken into consideration (Lee et al. 2002 and Bagchi et al. 2002) otherwise the kidney is badly ignored. However, quite earlier it was suggested that special caution should be taken in patients with liver and kidney disease while using paracetamol (Brzeznicka and Piotrowsi 1989).
BRIEF REVIEW OF EXISTING REPORTS
Only for brevity and convenience current status of knowledge on herbal drugs versus paracetamol poisoning is discussed under following separate headings:
1. Many factors enhance paracetamol toxicity:
Alcohol, many drugs rifampicin, phenobarbital, isoniazid, phenytoin and carbamazepin increase paracetamol toxicity (Whitecomb and Block, 1994: Willacy, 2007). Even fasting greatly increases the chances of liver damage by paracetamol (White comb and Block, 1994). Tobacco is found as an independent risk factor in paracetamol poisoning (Schmidt and Dalhoff, 2003).
2. Some herbal drugs can reduce paracetamol toxicity
Chinese medicine Artemisia asiatica. & A. Maritima (DA-9601) has been reported to reduce liver damage induced by paracetamol (Ryu et al., 1998, Janbaz and Gilani, 1995). Another chinese herbal medicine 'gomsin-A', a lignan component of Schisandra chinesis has also been reported to be hepatoprotective against paracetamol. It must be noted that inadequate clinical research with human subjects has been conducted on these herbal drugs to confirm the value of these herbal therapies against the toxic side effects of paracetamol (IBIS medical com., 2000). A literature review on herb-drug interaction also mentions that reported herb-drug interactions were based on case reports and were of limited clinical observations (Hu et al., 2005). On account of such badly ignored limited clinical observations on herb-drug interaction so far no herbal paracetamol combination drug could be made. On the contrary recently nitroparacetamol (NCX-701) has been introduced as a novel analgesic drug (Sandoval et al., 2007). Silybum marianum (milk thistle) reduces paracetamol induced hepatotoxiciy in animals. This is a well research herbal drug in animals and humans and has good future (Pradhan and Girish, 2006) but its preventive action towards kidney needs detail studies.
3. Problem in developing country like India:
In developing country like India where self medication with herbal and other drugs without prescription is a common practice hence chances of accidental or intentional overdose always exists. Moreover general public is not aware of drug abuse and its antidotal management under such circumstances paracetamol induced liver and kidney damage may go unnoticed and affected individual may die. Citizen and villagers know use paracetamol but none of them know about its hepatonephrotoxicity and about its principal antidotal drug N-acetylcysteine.Liver transplantation is also out of reach of general public. This drug is effective only when administrated within 10 hours of paracetamol poisoning and this drug is not available every where in India.
It is needless to say that paracetamol induced hepatonephrotoxicity and its management with herbal drugs also deserves serious attention, no matter, renal insufficiency occurs in about 1-2 percent cases of paracetamol overdose.
Authors respectfully thank Council of Scientific and Industrial Research, New Delhi for providing fellowship and grants to Miss Anjali Sharma and to University Grants Commission, New Delhi for providing Rajiv Gandhi National Fellowship and grants to Mr. Mukesh Makwana. Departmental Facilities are also acknowledged.
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