ORIGINAL ARTICLE
Year : 2010  |  Volume : 17  |  Issue : 2  |  Page : 64-66 Table of Contents     

Acetaminophen-induced Hepato- and nephrotoxicity and amelioration by silymarin and Terminalia chebula in rats


Department of Pharmacology and Toxicology, College of Veterinary Science, Hyderabad - 500030, Andhra Pradesh, India

Date of Web Publication24-Nov-2010

Correspondence Address:
A Gopala Reddy
Department of Pharmacology and Toxicology, College of Veterinary Science, Hyderabad - 500030 (AP)
India
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DOI: 10.4103/0971-6580.72672

PMID: 21170247

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   Abstract 

Experimental study was conducted to evaluate the hepato- and renoprotective effect of silymarin and Terminalia chebula against experimentally-induced acetaminophen (APAP) toxicity in rats. Oral administration of APAP @ 500 mg/kg for 1 to 3 days to all the four groups (six rats in each) resulted in significant elevation of serum triglycerides, total cholesterol, blood urea nitrogen, serum creatinine, and aspartate transaminase activity. Post-treatment with silymarin @ 25 mg/kg and T. chebula 125 mg/kg in groups 2 and 3 and their combination to group 4 from day 4 to 14 has significantly reversed the alterations of above said markers and offered better protection. The results of the study enunciated that silymarin and T. chebula exhibit good hepato- and nephro-protection against APAP toxicity.

Keywords: Acetaminophen, hepatotoxicity, nephrotoxicity, silymarin, Terminalia chebula


How to cite this article:
Gopi K S, Reddy A G, Jyothi K, Kumar B A. Acetaminophen-induced Hepato- and nephrotoxicity and amelioration by silymarin and Terminalia chebula in rats. Toxicol Int 2010;17:64-6

How to cite this URL:
Gopi K S, Reddy A G, Jyothi K, Kumar B A. Acetaminophen-induced Hepato- and nephrotoxicity and amelioration by silymarin and Terminalia chebula in rats. Toxicol Int [serial online] 2010 [cited 2016 Aug 31];17:64-6. Available from: http://www.toxicologyinternational.com/text.asp?2010/17/2/64/72672


   Introduction Top


Liver diseases remain one of the serious health problems. Hepatic dysfunction due to ingestion or inhalation of hepatotoxin is increasing worldwide. [1] Acetaminophen (APAP; paracetamol-[PCM]) is commonly prescribed analgesic and antipyretic drug producing dose-dependent hepato- and nephrotoxicity. Herbal alternatives are one of the best ways to minimize liver damage and were used prophylactically and also as antidotes. Silymarin, a flavonolignan obtained from Silybum marianum, comprises of silybin as the most active component that counteracts the leakage of alanine transaminase (ALT) and gamma glutamyl transferase and prevent lipid peroxidation (LPO). [2] The fruits of Terminalia chebula were used as common household remedy, [3] and its phenolics prevent nickel chloride-induced oxidative stress by decreasing LPO, restoring the activity of glutathione-S-transferase, glutathione reductase, and glutathione peroxidase. [4] The present investigation was carried out to study the hepato- and renoprotective effects of silymarin and T. chebula.


   Materials and Methods Top


A total of 24 male Wistar kyoto rats (200 - 250 g) were obtained from National Institute of Nutrition, Hyderabad. The animals were maintained and used in accordance with guideline of the Control and Prevention Supervision Committee Experimental on Animals, and the protocols were accepted by Instituitional animal ethics committee (IAEC). The rats were randomly divided into four groups of six rats in each; APAP @ 500 mg/kg was administered to all the groups from 1 to 3 days. Group 1 served as toxic control and was maintained with distilled water from 4 to 14 days. Groups 2 and 3 were administered orally with silymarin (25 mg/kg) and T. chebula (125 mg/kg) from 4 to 14 days. Group 4 was administered with a combination of silymarin + T. chebula at the doses mentioned in groups 2 and 3, respectively. The experiment was carried out for 14 days.

The sera samples were separated from blood on day 0, 4, and 14 for the estimation of triglycerides, total cholesterol, blood urea nitrogen (BUN), serum creatinine, and aspartate transaminase (AST) activity by using commercially available diagnostic kits (Qualigens Pvt. Ltd, Mumbai, India). All data were expressed as means ± SE. The means were analyzed by One Way Analysis of Variance (ANOVA) by using SPSS software package. Values of P<0.05 were considered as significant.


   Results and Discussion Top


The activity of AST (U/L) [Table 1] and concentration of triglycerides (mg/dl) and total cholesterol (mg/dl) [Table 2] were significantly (P<0.05) elevated on day 4 in groups 1, 2, 3, and 4 as compared with the mean values of day 0, and these observations coincided with earlier studies where oral administration of PCM at 750 mg/kg/day for 7 days increased the level of liver marker enzymes viz., AST, ALT, Alkaline phosphatase (ALP), creatinine, and BUN. [5] Following administration with silymarin and T. chebula in groups 2, 3, and 4, the levels were significantly (P<0.05) reduced on day 14 as compared with that of hepatotoxic control.
Table 1: Aspartate transaminase activity (U/l) in different groups of rats

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Table 2: Serum triglycerides and total cholesterol concentration in different groups of rats

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In the current investigation, renal biomarkers like BUN (mg/dl) and serum creatinine (mg/dl) were significantly (P<0.05) elevated on day 4 in groups 1, 2, 3, and 4 [Table 3] as compared with the mean values of day 0. The N-acetyl-p-benzoquinoneimine, a reactive metabolite of APAP that causes oxidative damage to tissues, might be the reason for its renotoxic effects. [6] At the end of treatment on day 14, the BUN level was significantly (P<0.05) decreased in groups 2, 3, and 4. However, groups treated with silymarin (group 2) and silymarin + T. chebula (group 4) showed a significant (P<0.05) decrease in BUN level when compared with T. chebula alone treated group (group 3) at 14 th day [Table 3]. Nonprotein nitrogenous substances such as BUN and serum creatinine are increased only when renal function is below 30% of its original capacity. An increase in BUN reflects an accelerated rate of protein catabolism.[7] Cytochrome P450-mediated toxic metabolite of acetaminophen binds with cell macromolecules, which might be the reason for its nephrotoxic effects. [6] The beneficial effects of the drugs in test may be attributed to free radical scavenging activity of T. chebula[8] and renoprotective effects of T. chebula. [9] Silymarin has been reported to possess protective action on kidney cells against PCM-induced toxicity. [10]
Table 3: Blood urea nitrogen and serum creatinine concentration in different groups of rats

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   References Top

1.Wogan GN. The induction of liver cell cancer by chemical. In: Cameron HM, Linsell DH, Warwick GP, Editors. Liver cell cancer. Amsterdam: Elsevier scientific; 1976. p. 21-52.  Back to cited text no. 1
    
2.Letteron P, Labbe G, Degott C, Berson A, Fromentry B, Decaforge M, et al. Mechanism of protective effects of silymarin against carbontetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Biochem Pharmacol 1990;39:2027-34.   Back to cited text no. 2
    
3.Kirtikar KR, Basu BD. Terminalia chebula In: Indian Medicinal Plants. 2 nd ed. Allahabad: India Lolit Mohan Basu Publication; 1935. p. 1020-3.  Back to cited text no. 3
    
4.Prasad L, Husain Khan T, Jahangir T, Sultana S. Chemomodulatory effects of Terminalia chebula against nickel chloride induced oxidative stress and tumor promotion response in male Wistar rats. J Trace Elem Med Biol 2006;20:233-9.  Back to cited text no. 4
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5.Zaher A, Hady H, Mahmoud M, Farrag M. The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage. Toxicol 2008;243:261-70.  Back to cited text no. 5
    
6.Richie JP Jr, Long CA, Chen TS. Acetaminophen-induced depletion of glutathione and cysteine in aging mouse kidney. Biochem Pharmacol 1992;44:129-35.  Back to cited text no. 6
    
7.Kaneko JJ, Harvey JW, Michael LB. Clinical Biochemistry of Domestic Animals. 5 th ed. New York: Academic Press; 1997. p. 182-9, 857-79.  Back to cited text no. 7
    
8.Lee HS, Won NH, Kim KH, Lee H, Jun W, Lee KW. Antioxidant effects of aqueous extract of Terminalia chebula in vivo and in vitro. Biol Pharmaceutical Bull 2005;28:1639-44.   Back to cited text no. 8
    
9.Rao NK, Nammi S. Antidiabetic and renoprotective effects Terminalia chebula Retz. Seeds in streptozotocin-induced diabetic rats. BMC Complement Altern Med 2006;6:17.  Back to cited text no. 9
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10.Deák G, Müzes G, Láng I, Nékαm K, González-Cabello R, Gergely P, et al. Effects of two bioflavanoids on certain cellular immune reactions. Acta Physiol Hung 1990;76:113-21  Back to cited text no. 10
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]


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