Protective effect of Andrographis paniculata and andrographolide on cyclophosphamide-induced urothelial toxicity.
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 microg/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 N2 level, 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-alpha, 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-gamma during CTX treatment was elevated by the administration of A paniculata and ANDLE.
Sheeja
K
K
Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.
Kuttan
Girija
G
D035685:Andrographis; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D004224:Diterpenes / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D020011:Protective Agents / Q000627:therapeutic use*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology*
D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D010936:Plant Extracts; D020011:Protective Agents; C030419:andrographolide; D003520:Cyclophosphamide