**1. Introduction**

The liver plays an astonishing array of vital functions in the maintenance and perform‐ ance of the body. Additionally, it is also handling the metabolism and excretion of drugs and other xenobiotics from the body thereby providing protection against foreign substan‐ ces by detoxifying and eliminating them (saleem et al., 2010). Large numbers of xenobiot‐ ics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents such as proteins, lipids, RNA and DNA (Ajith *et al.,* 2007). A growing international health concern is Tuberculosis caused by *Mycobacterium tuberculosis* (Abdelaal *et al.,* 2009).India is the highest TB burden country accounting for one fifth (21%) of the global incidence (WHO, 2010). The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF), pyrazina‐ mide (PZA) and Ethambutol(ETH)continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis (Eminzade *et al.,* 2008). This is one of the most serious adverse effects of anti-tuberculosis drugs (ATD). Liver injury or liver dysfunction is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies (saleem *et al.,* 2010). It has great capacity to detoxify and synthesize useful substances, and therefore damage to the liver has grave consequences (Devaraj *et al*., 2011). Currently, there is no effective treatment against ATD induced hepatic damage. Plants are an important component of the health

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care system in India and have been found to be effective in the treatment of different diseases and are the beacon of the therapeutic sources for curing diseases from times immemorial (Merina *et al.,* 2012). *Phyllanthus amarus* Linn. is commonly known as *bhumi amla* (Joshi&Parle2007). It is reported to possess antiviral (Lee *et al.,* 1996), anticancer (Rajeshkumar *et al.,* 2002). But there is no scientific evidence for its hepatoprotective activity against ATD induced liver injury. Hence the present study was undertaken to explore the key behind the use of *P.amarus* as a hepatoprotective formulation against xenobiotics induced hepatic adverse effect.

Group I: Control (normal saline, 0.9%).

3days/week.

b.w., (p.o) 3days/week.

ical and histological analysis.

*2.4.1. Blood biochemical investigations*

*2.4.2. Tissue biochemical investigations*

*2.4.3. Histopathological investigations*

1974 respectively.

and Eosin (H & E).

**2.5. Statistical analysis**

Group II: *Per se* - 400mg/kg, b.w., *P.amarus* (p.o.), daily.

Group VIII: Positive control-Silymerin -50mg/kg b.w. (p.o.), daily.

Elvejham homogenizer at 600-1000 rpm in ice cold conditions.

Group III: Experimental control-RIF+INH+PZA+ETH at 52, 70,175,140 mg/kg, b.w., (p.o.),

Hepatoprotective effect of *Phyllanthus amarus*

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Group VI- VII: INH+RIF+PZA (as in group III) + *P.amarus* at 100, 200, 300 and 400 mg/kg,

All the animals were euthanized 24hours after the last treatment to perform various biochem‐

Blood was drawn from retro-orbital venous sinus and serum was isolated. Serum Urea, Uric acid and Creatinine determined by commercially prepared kit method (E-Merck, Germany).

The tissues viz., liver and kidney were quickly excised, washed in ice cold, normal saline and blotted individually freed from extraneous material on ash-free filter paper. The tissues were then homogenized separately in hypotonic buffer (0.008% NaHCO3), pH 7.4, using a Potter-

The crude tissue homogenate was centrifuged at 2000 rpm for 15 min (0-4°C). The supernatant was collected and stored at- 20°C until used for estimating tissue biochemi‐ cal parameters. Lipid Peroxidation (LPO) was determined by measuring thiobarbituric acid reactive substances (TBARS) in tissues according to Sharma and Krishnamurthy, 1968.SOD and Catalase activity were determined according to Misra and Fridovich, 1972 and Aebi,

Tissues were fixed with Bouin's solution. They were later sectioned using a microtome, dehydrated in graded alcohol, embedded in paraffin section, and stained with hemotoxylin

Results are presented as mean ± S.E. of six animals used in each group. Data were subjected to statistical analysis through one-way analysis of variance (ANOVA) at 5% significance level

followed by Student's t-test at p≤ 0.05( Snedecor and Cochran,1989).

Serum AST and ALT activity were determined with Reitman and Frankel, 1957.
