Protective effect of Azadirachta indica A. Juss against doxorubicin-induced cardiac toxicity in tumour bearing mice.

Doxorubicin (DOX) treatment (12 µg/g body weight, once a week for 2 weeks) resulted in a significant decrease in the heart rate along with an increase in QRS, ST, and QT intervals. Histopathological studies showed cardiomyocyte degeneration, cytoplasmic vacuolation and macrophage infiltration in cardiac tissue. A marked increase in the rate of apoptosis was also observed. An increased oxidative stress was evidenced by significantly higher levels of lipid peroxidation (LPO) and depletion of reduced glutathione. A decrease in the activity of cellular antioxidant defence enzymes was also observed. The decrease in the heart rate and ECG alterations were prevented significantly by AAILE (100 µg/g body weight, po) co-treatment, started two weeks prior to DOX treatment and continued till the termination of the experiment. The cardioprotection was also evident from histopathology and decrease in the rate of apoptosis in cardiomyocytes. AAILE co-treatment also prevented DOX-induced increase in LPO and decrease in antioxidant defence enzymes. The results suggest that AAILE administration prevents DOX-induced cardiotoxicity.

Azadirachta indica mitigates DMBA-induced hepatotoxicity: A biochemical and radiometric study.

The hepatoprotective potential of aqueous Azadirachta indica leaf extract (AAILE) was assessed against DMBA-induced hepatotoxicity. DMBA  (7,12-dimethylbenz[a] anthracene) treatment (40 mg/kg body weight, ip) to male Balb/c mice resulted in the derailment of liver function as revealed by extremely slow clearance of 99mTc-mebrofenin from liver, elevated levels of alkaline phosphatase (ALP) and alanine transaminase (ALT), compared to control group. In addition, elevated micronuclei score and high apoptotic index indicated hepatogenotoxicity in DMBA-treated mice. DMBA treatment also upregulated cytochrome P450 (CYP), cytochrome b5 (Cyt b5) and decreased glutathione-S-transferase activity in hepatic tissue, compared to control group. Enhanced lipid peroxidation (LPO) levels along with decreased reduced glutathione (GSH) level were also observed in DMBA group, compared to control group. AAILE co-treatment (200 mg/kg body weight, po, thrice a week) for 8 weeks followed by DMBA injection showed significant improvement in hepatic status, as revealed by normalization of 99mTc-mebrofenin clearance rate, decreased ALP and ALT levels, reduced genotoxicity in terms of micronuclei score and apoptotic index. Levels of LPO were significantly decreased along with increased hepatic GST and GSH levels in AAILE + DMBA group, compared to DMBA group. However, no significant change was observed in hepatic CYP and Cyt b5 levels, compared to DMBA group. The results indicated that AAILE effectively ameliorated DMBA-induced hepatotoxicity.