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RESEARCH LETTER
Year : 2006  |  Volume : 38  |  Issue : 3  |  Page : 209-210
 

Impact of umbelliferone (7-hydroxycoumarin) on hepatic marker enzymes in streptozotocin diabetic rats


Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India

Correspondence Address:
K V Pugalendi
Department of Biochemistry, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.25813

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How to cite this article:
Ramesh B, Pugalendi K V. Impact of umbelliferone (7-hydroxycoumarin) on hepatic marker enzymes in streptozotocin diabetic rats. Indian J Pharmacol 2006;38:209-10

How to cite this URL:
Ramesh B, Pugalendi K V. Impact of umbelliferone (7-hydroxycoumarin) on hepatic marker enzymes in streptozotocin diabetic rats. Indian J Pharmacol [serial online] 2006 [cited 2019 Dec 9];38:209-10. Available from: http://www.ijp-online.com/text.asp?2006/38/3/209/25813


Diabetes mellitus is by far the most common of endocrine disorders and a major threat to health care, worldwide. The increase of free radical mediated-toxicity is well documented in streptozotocin (STZ)-diabetic rats. The liver is the main effector organ for maintaining plasma glucose levels within narrow limits. Hyperglycemia can generate a redox imbalance inside the cells, especially in the liver.[1] A model antidiabetic drug should possess both hypoglycemic and antioxidant properties, without any adverse effects. Plant drugs are frequently considered to be less toxic than synthetic ones.

Plant derived phenolic coumarins might play a role as dietary antioxidants because of their presence in the human diet, especially in fruits and vegetables.[2] Umbelliferone (UMB, 7-hydroxycoumarin), a benzopyrone in nature, is a derivative of coumarin. Our previous studies have shown that UMB had both antihyperglycemic[3] and antioxidant[4] properties in diabetic rats. The objective of the present study is to analyze the effect of UMB on serum hepatic marker enzymes, total protein, liver weight and glycogen content in STZ-diabetic rats. The structure of UMB is depicted below.

Male Wistar albino rats (weight 180-200 g) were procured from the Central Animal House, Department of Experimental Medicine, Rajah Muthiah Medical College and Hospital, Annamalai University. The study was carried out in accordance with Indian National Law on Animal Care and Use and was approved by the Ethical Committee of Rajah Muthiah Medical College and Hospital (Reg. No: 160/1999/CPCSEA*), Annamalai University, Annamalainagar, Tamil Nadu, India.

Streptozotocin was purchased from Sigma-Aldrich, St. Louis, USA. UMB was procured from Carl Roth GmbH & Co, Germany.

After an overnight fast, the rats were injected with a single dose of STZ (40 mg/kg, b.w.) intraperitoneally (i.p.). The animals with blood glucose above 235 mg/dL were considered to be diabetic and used for the experiment.

The animals were randomly divided into 5 groups of six animals each, as given below. Dimethyl sulphoxide (DMSO) was used as a vehicle.

Group I: Normal control received 10% DMSO (i.p.) only.

Group II: Normal + UMB (30 mg/kg/b.w., i.p.) in 10% DMSO.

Group III: Diabetic control (10% DMSO (i.p.)).

Group IV: Diabetic + UMB (30 mg/kg/b.wt., i.p.) in 10% DMSO.

Group V: Diabetic + glibenclamide (600 µg/kg/b.w., i.p.) in 10% DMSO.

After 45 days of treatment, the 12 h-fasted animals were sacrificed by decapitation. Blood was collected for the estimation of hepatic marker enzymes and total proteins. The liver was collected for the determination of weight and glycogen content. The activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) and the level of total proteins were estimated by using commercially available kits (Boehringer Mannheim, Mannheim, Germany). The activity of gamma glutamyl transferase (GGT) was measured by the method of Rosalki and Rau.[5] The level of liver glycogen was estimated by the method of Morales et al.[6]

The results are expressed as mean ± SD (n=6 rats/ group). [Table - 1] Data were analysed by one-way analysis of variance (ANOVA), followed by Duncan's multiple range test (DMRT). The statistical significance was set at P <0.05.

A marked decrease in liver weight was observed in diabetic rats, [Table - 1] which may be due to an increased glycogen breakdown and gluconeogenesis with protein degradation. Protein synthesis decreases in the absence of insulin, partially because the transport of amino acids into muscle is diminished (amino acids serve as gluconeogenic substrate). Thus, insulin deficient persons are in negative nitrogen balance.[7] Treatment with UMB elevated liver weight, glycogen content and plasma proteins, which may be due to increased plasma insulin[3] level. Insulin favours glycogenesis and generally has an anabolic effect on protein metabolism, in that, it stimulates protein synthesis and retards protein degradation.

Enzymes directly associated with the conversion of amino acids to keto acids are ALT and AST. ALT and AST activities are used as the indicators of hepatocyte damage.[8] Diabetic rats have increased activities of these enzymes, which may be due to hepatic damage and deficiency of insulin. Insulin suppresses the genes encoding gluconeogenic enzymes. ALT is a gluconeogenic enzyme and it is possible that ALT is an indicator of impaired insulin signalling. Treatment with UMB decreased the activities of these enzymes, by its insulin secretory and antioxidant properties.

ALP is present in all tissues of the body, especially in the cell membrane and the levels are high in the liver, kidney, bone and placenta. New enzyme synthesis mainly occurs in the hepatocytes adjacent to the biliary canaliculi. In our study, the activity of ALP increased in diabetic rats as compared with normal control rats, which could be due to an increased release from the hepatocytes damaged by diabetes-induced oxidative insult. In UMB treated rats, the activity of ALP also reversed to near normal level.

GGT reflects the biliary tract function and may act to transport amino acids and peptides into the cells, in the form of gamma glutamyl peptides. Perry et al [9] have reported that high level of hepatic enzyme, GGT, is associated with later development of diabetes. In our study, the activity of GGT increased, which may be associated with diabetes. Treatment with UMB reversed the activity of GGT, which reflects the strong protective effect of UMB. Thus, our results have shown that treatment with UMB reversed hepatic marker enzymes, total proteins, liver weight and glycogen content to near normalcy. It reflects that UMB has a protective effect against liver cell damage in STZ-diabetic rats.

 
  References Top

1.Gallou G, Ruelland A, Legras B, Maugendre D, Allanic H, Cloarec L. Plasma MDA in type 1 and type 2 diabetes. Clin Chim Acta 1993;214:227-34.  Back to cited text no. 1    
2.Hoult JRS, Paya M. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996; 27:713-22.  Back to cited text no. 2    
3.Ramesh B, Pugalendi KV. Antihyperglycaemic effect of umbelliferone in STZ-diabetic rats. J Med Food 2005 (Accepted).  Back to cited text no. 3    
4.Ramesh B, Pugalendi KV. Impact of umbelliferone on erythrocyte redox status in STZ-diabetic rats. Yale J Biol Med (Accepted).  Back to cited text no. 4    
5.Rosalki SB, Rau D. Serum g-glutamyl transpeptidase activity in alcoholism. Clin Chim Acta 1972;39:41-7.  Back to cited text no. 5  [PUBMED]  
6.Morales MA, Jabbay AJ, Tenenzi HP. Mutation affecting accumulation of glycogen. Neurospora News Lett 1973;20:24-5.  Back to cited text no. 6    
7.Murray RK, Granner DK, Mayes PA, Rodwell VW, editors. Harper's Biochemistry. 25th ed. Appleton and Lange Stanford: Connecticut; 2000. p. 610.  Back to cited text no. 7    
8.Whitehead MW, Hawkes ND, Hainsworth I, Kingham JG. A prospective study of the causes of notably raised aspartate transaminase of liver origin. Gut 1999;45:129-33.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Perry IJ, Wannamethee SG, Shaper AG. Prospective study of serum gamma-glutamyltransferase and risk of NIDDM. Diabetes Care 1998;21:732-7.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]


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