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Protective Effect of Andrographis paniculata and Andrographolide on Cyclophosphamide-Induced Urothelial Toxicity

Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India, amalaresearch{at}rediffmail.com

Girija Kuttan, PhD

Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.

The protective effect of Andrograhis paniculata and andrographolide (ANDLE) against cyclophosphamide (CTX)-induced urothelial toxicity was investigated in this study. Pretreatment of Swiss albino mice with A paniculata extract (10 mg/dose/animal intraperitoneally [ip]) and ANDLE (500 µg/dose/animal ip) could significantly reduce CTX (1.5 nmol/kg body weight)-induced urothelial toxicity. Morphological and histopathological analysis of urinary bladder of CTX-treated mice showed severe inflammation and dark coloration, whereas A paniculata and ANDLE-treated mice showed almost normal bladder morphology. Elevation of urinary protein level (7.33±0.3 g/L) by CTX administration was reduced by A paniculata (3.78 ± 0.4 g/L) and ANDLE treatment (4.19 ± 0.1 g/L). Urinary urea N₂level, which was elevated after 48 hours of CTX administration (24.25 ± 0.2 g/L) was found to be reduced by the treatment with A paniculata (14.19 ± 0.5 g/L) and ANDLE (15.79 ± 0.4 g/L). A decreased level of reduced glutahione (GSH) content in liver (2.81 ± 0.1 nmol/mg protein) and bladder (1.20 ± 0.2 nmol/mg protein) after CTX administration was also increased by the treatment with A paniculata (liver: 5.78 ± 0.3 nmol/mg protein; bladder: 2.96 ± 0.2 nmol/mg protein) and ANDLE (liver: 5.14 ± 0.3 nmol/mg protein; bladder: 2.84 ± 0.2 nmol/mg protein). Production of the proinflammatory cytokine, tumor necrosis factor-, which was elevated during CTX administration, was found to be inhibited by A paniculata and ANDLE treatment. The lowered level of interleukin-2 and interferon- during CTX treatment was elevated by the administration of A paniculata and ANDLE.

Key Words: Andrographis paniculata • andrographolide • cyclophosphamide • urothelial toxicity • MESNA • cytokines

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