الفهرس 
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Abstract
Drug rifampicin is the most common of pharmaceuticals for use in the treatment of chest diseases (tuberculosis). It was found that treatment with the drug leads to some complications in humans and also in experimental animals such as hepatic and renal morbidity. However, its clinical and experimental use is hampered by several side effects, among which, hepatotoxicity and nephrotoxicity are of the most disquieting side effects.
The present study has been conducted to evaluate the protective effect of aqueous and ethanolic extracts of Azadirachta indica (Family Meliaceae or mahogany family) on RMP-incuced hepatotoxicity and nephrotoxicity in experimental rats.
Animals were divided in to six groups designated as follows:
1-group I (normal control); each animal was orally given the equivalent volume of the CMC (1% w/v), six days per week for four weeks by gastric intubation.
2-group II (normal treated with aqueous extract) is given the aqueous extract at dose level of 100 mg/kg b.wt.3 times (every other day) /4 weeks.
3-group III (normal treated with ethanolic extract) is given the ethanolic extract at dose level of 100 mg/kg b.wt.3 times (every other day) /4 weeks.
4-group IV (rifampicin control) is given 0.5g/kg b. wt rifampicin dissolved in CMC (1% w/v), six days per week for four weeks by gastric intubation.
5-group V (rifampicin group treated with aqueous extract) is given aqueous extract at dose level of 100 mg/kg b .w. 3 times (every other day) / 4 weeks and 0.5 g/kg rifampicin 6 times / 4 weeks.
6-group VI (rifampicin group treated with ethanolic extract) is given ethanolic extract at dose level of 100 mg/kg b .w. 3 times (every other day) / 4 weeks and 0.5 g/kg rifampicin 6 times / 4 weeks .
All treatments were applied orally by gastric intubation.
RMP-administered group is compared with normal one, groups 2 and 3 are compared to normal group and RMP-administered group treated with aqueous and ethanolic extracts of neem are compared with RMP-administered control group.
Results showed that RMP caused a marked elevation in serum enzymes (ALT, AST, LDH and ALP) activities and total bilirubin level together with a significant decrease in serum levels of total protein, globulin and albumin. Concomitant with these biochemical changes, remarkable histopathological alterations in liver tissue were observed in RMP-administered animals, which exhibited inflammatory cells infiltration in the portal area in addition to few fatty degenerative changes in the hepatocytes and focal degenerated areas of the parenchyma. The treatment of these animals with aqueous and ethanolic extracts of neem, successfully prevented most of these biochemical and histological alterations. Concerning oxidative stress and antioxidant defense system the depleted hepatic total thiol and glutathione contents as well as the decreased hepatic glutathione peroxidase (GPx), glutathione-S-transferase (GST), catalase (CAT) and peroxidase activities of RMP-administered rats were potentially increased as a result of the two treatments.
The RMP-induced nephrotoxicity was evidenced by elevations in serum biochemical variables related to kidney dysfunction (creatinine, creatinine clearance and uric acid concentrations). The treatment of RMP-administered rats with aqueous and ethanolic extracts of neem decreased the elevated levels of serum creatinine and uric acid induced by RMP-administration. Concerning oxidative stress and antioxidant defense system, the depleted kidney total thiol content was significantly increased in the case of aqueous and ethanolic extracts treatments. Moreover, the decreased activities of kidney GST, SOD, CAT and peroxidase activities were significantly improved as a result of the two treatments. GPx activity and glutathione were decreased significantly in the treatment as compared with RMP-administered control group.
In conclusion, rifampicin treatment increases the formation of oxygen free radicals and reduces antioxidants. Aqueous and ethanolic extracts of neem have potential chemoprotective effects against RMP-induced hepatotoxicity and nephrotoxicity. These ameliorative chemopreventive effects may be mediated via improving the antioxidant defense system and suppressing the oxidative stress and production of free radicals.