الفهرس 
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Abstract
Drug-induced liver toxicity may be a common reason behind liver injury. It accounts for about one-half of the cases of acute liver failure and mimics all types of acute and chronic disease. Rifampicin (Rif) is a recognized therapeutic and preventive agent against tuberculosis. However, high rates of many side effects and symptoms associated with hepatotoxicity have identified throughout the treatment.
It’s believed that natural products are a good source of natural antioxidants which exert their effect by reducing the formation of the final active metabolite of the drugs or by scavenging the reactive molecular species to stop their reaching a target site. Herbal medicine is free from side effects and fewer pricey in comparison to synthetic drugs. Also some emphasis has been placed on the antioxidant properties of Annona Squamosa and N-acetylcysteine.
The present study is designed to evaluate the effect of Annona squamosa Linn (MEAS) or/and N-Acetyl Cysteine (NAC) on Anti-tuberculosis drug Rifampicin -induced hepatotoxicity in male rats. Fifty adult male rats weighing 120-150 g. used throughout the experimental duration of 21 days were divided into five groups:
-group 1 (control): rats served as a negative control group and received the solvent of Rif.
-group II (Rif): rats were treated orally with Rif (300mg/kg b.wt.) once daily for 21 days and served as a positive control group.
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Summary
-group III (Rif+MEAS): rats were treated orally with Rif (300mg/kg b.wt.) and MEAS (500mg/kg b.wt.), 1h before Rif treatment, once daily for 21 days.
-group IV (Rif+NAC): rats were treated orally with Rif (300mg/kg b.wt.) and NAC (100mg/kg b.wt.), ½ h before Rif treatment, once daily for 21 days.
-group V (Rif+MEAS+NAC): rats were treated orally with Rif (300mg/kg b.wt.) and MEAS (500mg/kg b.wt.), 1h before Rif treatment, and NAC (100mg/kg b.wt.), ½ h before Rif treatment, once daily for 21 days.
At the end of the experiment, all rats were sacrificed under ether anaesthesia. The blood samples were collected and centrifuged for biochemical analysis included bilirubin, total protein, albumin, ALT, AST, ALP. Then the liver specimens obtained from control and treated rats were divided into two parts, the first part was homogenized and the supernatant was collected and stored at- 80o C for the assay of γ-GT, MDA, GSH, IL-6, IL-10, Bcl2, and 8-OHdG. The second part was prepared for histopathological studies.
The results obtained from the present study can be summarized as follows:
-The Rif group that received MEAS or/and NAC showed a significant decrease compared with the Rif group in the levels of serum bilirubin, ALT, AST, ALP and hepatic γ-GT levels.
-The levels of hepatic MDA, IL-6, and 8-OHdG showed a significant decrease compared with the Rif group
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-Rif group that received MEAS or/and NAC showed a significant increase in the content of serum total protein, albumin, the level of hepatic GSH, IL-10, and Bcl2.
-In addition, the lesions in liver section were reduced and Kupffer cell activation was recorded in the Rif groups received MEAS or NAC.
-However, slight necrosis was still noticed in both groups and slight inflammations and vacuolar degeneration were noticed in the Rif group received MEAS.
- Additionally, the Rif group that received MEAS and NAC showed a great amelioration in the liver histological structure.
- On the other hand, the Rif group showed a highly significant increase compared with the control group in the marker levels of serum bilirubin, ALT, AST, ALP, and hepatic γ-GT, as well as, the levels of hepatic MDA, IL-6, and 8-OHdG.
-While a significant decrease in serum levels of total protein, albumin, the level of hepatic GSH and inflammatory markers levels IL-10 and Bcl2 were recorded.
Additionally, the liver tissue of the Rif-treated rats showed necrotic lesions, degeneration of hepatocytes with pyknosis, pathological alterations of the portal triad with thickened dilated and congested portal vein surrounded by scattered leucocytic inflammatory cells and disorganized hepatic strands with dilated blood sinusoid.
In conclusion, methanolic extract of Annona Squamosa Linn or/and N-Acetyl Cysteine were effective in inhibiting the
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Summary
Rifampicin induced hepatotoxicity in the rat model. Possible mechanisms for antioxidant effects of methanolic extract of Annona Squamosa Linn and N-Acetyl Cysteine shown in the current study in the Rifampicin -treated rats are there ability to modulate the hepatic oxidative stress, inflammation and apoptosis.