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Vol. 3 (1) Jan Mar 2012 www.ijrpbsonline.com 110

International Journal of Research in Pharmaceutical and Biomedical Sciences ISSN: 2229-3701

_________________________________________Research Paper

Protective Effect of Aqueous Extract of Uraria Picta on

Acetaminophen Induced Nephrotoxicity in Rats

Kale R. H.1*

, Halde U. K.2

and Biyani K. R.1

1Anuradha College of Pharmacy, Chikhli, Maharashtra, India.

2Drug Testing Laboratory, Government Ayurvedic and Unani Pharmacy, Nanded,

Maharashtra, India.

__________________________________________________________________________________

ABSTRACT

Nephrotoxicity can be produced by the excess use of NSAID (Non steroidal anti-inflammatory drugs) like

Acetaminophen, it-induced liver necrosis and renal insufficiency occurs in approximately 12% of patients with

acetaminophen overdose. Uraria pictais one of the important constitutents among the ten herb formulation

called Dashmula. Its content flavonoid are known to exhibit a range of biological activities like anti-

inflammatory, anti-thrombotic, hepatoprotection properties due to their free radical scavenging ability.

Healthy wistar albino rats (180-240 g) divided into four groups each containing six rats. Group I was taken as anormal, group II treated with 2.5 g/kg Acetaminophen and group III and group IV treated withAqueous extract

of Uraria picta plus acetaminophen (250 and 500 mg/kg dose) administered for seven days. Treatment with

the aqueous extract of Uraria picta (250 and 500 mg/kg/body wt.) containing polyphenolic compound and

carbohydrates might be significantly reduces the elevated levels of urine urea and BUN levels and also

elevated levels of Serum Creatinine and Urine creatinine compared to acetaminophen group. The activity

elicited by the extract might be due to its ability to activate antioxidant enzymes. The findings suggest the

potential use of the aqueous extract of Uraria picta as a novel therapeutically useful nephroprotective agent.

Key Words:Acetaminophen, Histopathology, Nephrotoxicity, Uraria picta.

INTRODUCTION

Nephrotoxicity is a poisonous effect of somesubstances, both toxic chemicals and medication,

on the kidneys. There are various forms of toxicity,Nephrotoxicity should not be confused with the

fact that some medications have a predominantly

renal excretion and need their dose adjusted for thedecreased renal function. Mainly nephrotoxicitycan be produced by the excess use of NSAID (Non

steroidal anti-inflammatory drugs) like

Acetaminophen, it-induced liver necrosis and renalinsufficiency occurs in approximately 12% of

patients with acetaminophen overdose. Heavier

acetaminophen use was associated with anincreased risk of end-stage renal disease in a dose

dependent fashion1

.At therapeutic doses, acetaminophen is metabolized

via glucuronidation and sulfuration reactions

occurring primarily in the liver, and results inwater-soluble metabolites that are excreted via the

kidney. As a result of the metabolic conversion ofacetaminophen by the microsomal P-450 enzyme

system, a highly reactive intermediate, N-acetyl-

pbenzoquinone imine (NAPQI) is produced.NAPQI directly reacts with glutathione (GSH) and

at overdoses of acetaminophen, the depletion of

cellular GSH occurs. This allows NAPQI to bind tocellular proteins and initiate lipid peroxidation,

leading to renal injury previous studiesdemonstrated that acute APAP overdose increased

lipid peroxidation, endoplasmic reticulum stress.Paracetamol (also known as acetaminophen)

poisoning is due to metabolic activation of APAP

by renal P450 mixed-function oxidases, similarmechanism was proposed for thenephrotoxicity

2,3,4.

Uraria picta is one of the important constitutents

among the ten herb formulation called Dashmula, awell established Ayurvedic drug of the Indian

system of medicines for treating general fatigue,

oral sores and several gynaecological disorders5.

Its content flavonoid are known to exhibit a range

of biological activities like anti-inflammatory, anti-thrombotic, hepatoprotection properties due to

their free radical scavenging ability. These

observations support the mechanism ofnephrotoxicity induced by acetaminophen in

animals is partially related to the depletion of renalantioxidant system

6.


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METHODS AND MATERIALS

Plant material

Whole plant of Uraria picta Desv. was collected

from Shri. Ganesh Nursery Jeur Purender Pune and

also procure authentified aqueous extract of Uraria

pictaDesv. from Amsar Pvt. Ltd. Indore (MP). The

whole plant was authentified in Botany departmentof the Shivaji Science College Chikhli Dist.

Buldana (MS). India.

Animals

Male albino Wistar rat 6-8 weeks of age andweighing between (180240) gm were selected

from Anuradha College of pharmacy, Chikhli, Dist-Buldana (MS) India. They were housed in

polypropylene cages under the standard conditionsof temperature, pressure and humidity. (12 hrs lightand dark cycles, at 25 +

3C and 35-60%

humidity).The animals were maintained understandard condition as per CPCSEA guideline.

Animals were fed with standard normal pellet diet

and water ad libitum during the course of the

experiment, according to the guidelines of

Institutional Animal Ethical Committee (IAEC) ofAnuradha College of pharmacy, Chikhli, Dist-

Buldana (MS) India, registered under CPCSEA,India (Registration no. abc/751/03/CPCSEA).

EXPERIMENTAL DESIGN

Healthy wistar albino rats (180-240 g) divided intofour groups each containing six rats. Group I was

taken as a normal treated with normal saline, groupII treated with 2.5 g/kg Acetaminophen was kept as

a control (20% suspension in saline stabilized by

0.2% gum) by means of a stomach tube, group IIIand group IV treated with Aqueous extract of

Uraria picta plus acetaminophen (250 and 500mg/kg dose) administered for seven days. 48 hours

after the acetaminophen injection animals weresacrificed using ether anesthesia blood wascollected from each animal. Serum was used for the

determination of ureaand creatinine by Spandiagnostic kit (Span Diagnostics Ltd., India. The

elevation of urea and creatinine level in the serum

was taken as the index of nephrotoxicity.

EVALUATION OF RENAL FUNCTION

Blood and urine ureaUrea concentration in the blood and urine wereestimated by enzymatic method using Urease

enzyme kit (DAM kit) by colorimetric end point

method. Absorbance was read using

photometrically at wavelength 540 nm.

Serum and urine creatinine

Creatinine level in the serum and urine were

estimated by the alkaline picrate method using

creatinine kit method. (Jaffes modified kinetic

method) and the absorbance was read at 520 nm

(Span diagnostics Ltd).

Histopathological Study

The two animals from each group were sacrificedon the day of blood withdrawal and kidneys were

isolated. Tissue samples were immersed in10%formalin for at least 24 hr to fix the tissue, the

tissue was then embedded in paraffin wax,

sectioned and stained with haematoxylin and eosin.The sections were then viewed under the light

microscope for Histopathological changes.

Statistical analysis

The data were presented as Mean SD and the

statistical analysis by one way ANOVA followedby Dunnetts multiple comparison tests.

RESULTS AND DISCUSSION

Table 1 and 2 shows, urine urea and BUN levels

were significantly elevated in the acetaminophen

treated group compared to the normal group

indicating the induction of severe nephrotoxicity.Treatment with the aqueous extract of Uraria picta

(250 and 500 mg/kg/body wt.) containingpolyphenolic compound and carbohydrates might

be significantly reduces the elevated levels ofurineurea and BUN levels and also elevated levels of

Serum Creatinine and Urine creatinine compared to

acetaminophen group (P


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compared to the normal group (Group I).Moreover, oral administration of aqueous extract of

Uraria picta significantly (P


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Fig. 2:Uraria picta Plant

CONCLUSION

The Protection offered by the extract could havebeen due to the presence of polyphenolic and

carbohydrates compounds. The activity elicited bythe extract might be due to its ability to activate

antioxidant enzymes. The findings suggest the

potential use of the aqueous extract of Uraria picta

as a novel therapeutically useful nephroprotectiveagent. Therefore, further studies to elucidate their

mechanisms of action should be conducted to aid

the discovery of new therapeutic agents for thetreatment of renal diseases.

REFERENCES

1. Ahmed O and Zaher A. The potentialprotective role of alpha-lipoic acid against

acetaminophen-induced hepatic and renaldamage. Toxicology. 2008;243:261270.

2. Murphy D. Risk of Kidney Failure

Associated With the Use ofAcetaminophen, Aspirin and Nonsteroidal

Anti-inflammatory Drugs. New England

Journal of Medicine. 1994;22:01-64.3. Ghosh J and Das J. Acetaminophen

induced renal injury via oxidative stress

and TNF- production: Therapeutic

potential of arjunolic acid. Toxicology.2010;268:818.

4.

Thomas S. Paracetamol (Acetaminophen)

Poisoning. Pharmac Ther. 1993;60:91-120.

5. Anonymous. The Ayurvedic Formulary of

India, 2nd

ed. Govt. of India, Ministry ofHealth and Family Welfare, Department

of AYUSH, New Delhi. 2003:55.

6. Patwardhan B, Warude D, Pushpangadan

P, Bhatt N. Ayurveda and traditionalChinese medicine: a comparative overview.

Evid Based. Complement Alternat Med.

2005;2(4):465-473.7. Bennit WM, Parker RA, Elliot WC,

Gilbert D and Houghton D. Sex relateddifferences in the susceptibility of rat togentamicin nephrotoxicity. J Infec

Diseases. 1982;145:370-374.8. Mayne PD. The kidneys and renal calculi.

In: Clinical chemistry in diagnosis andtreatment. 6th ed. London: Edward Arnold

Publications. 1994:2-24.

9. Anwar S, Khan NA, Amin KMY andAhmad G. Effects of Banadiq-al Buzoor in

some renal disorders. 1999.

10. Venkatesan N, Punithavathi D andArumugam V. Curcumin preventsadriamycin nephrotoxicity. Pharmacol.

2000;129(2):231-234.

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