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

Abstract

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 ANDLEtreated 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 N 2 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-α, 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-γ during CTX treatment was elevated by the administration of A paniculata and ANDLE.

Hepatoprotective Effect of Andrographolide Against Hexachlorocyclohexane-Induced Oxidative Injury

“…A recent report by Sheeja and Kuttan 41 showed that cyclophosphamide-induced urothelial toxicity in mice via reactive oxygen species production and treatment with ANDLE resulted in elevated levels of GSH in the liver and bladder of cyclophosphamide-treated mice. Nitric oxide is a highly reactive free radical associated with the severity of cyclophosphamide-induced bladder injury.…”

“…Nitric oxide is a highly reactive free radical associated with the severity of cyclophosphamide-induced bladder injury. 41 Administration of ANDLE has been shown to reduce the level of nitric oxide metabolite and protect mice from cyclophosphamide-induced urinary bladder injury. 41 The results of the present study suggest that the antioxidative effect of ANDLE may be due to its ability to activate antioxidant enzymes that catalyze the reduction of oxidants and that its use for recovery of hepatic damage may be beneficial.…”

Protective effect of triterpenoid fractions from the rhizomes of Astilbe chinensis on cyclophosphamide-induced toxicity in tumor-bearing mice

“…Andrographolide (Sheeja and Kuttan, 2006), berberine, curcumin, isothiocyanates (Manesh and Kuttan, 2005), mesna, protein A, GSH, squalene (Senthilkumar et al, 2006), and 2 -mercaptopropionyl glycine have shown varying degrees of protection against CTX toxicity. It has also been reported that many plant extracts such as Andrographis paniculata (Sheeja and Kuttan, 2006), Ayurvedic Rasayana, Cassia occidentalis , Emblica officinalis , garlic, Ixora coccinea, Juglans regia (Haque et al, 2003), Phyllanthus amarus (Kumar and Kuttan, 2005), Tinospora cardiofolia, and Withania somnifera (Davis and Kuttan, 2001), have exhibited ameliorating effects on CTX toxicity. This demonstrates that plant extracts have great potential in reducing the toxicity of CTX and the search for other such agents is vital to the management of side effects of CTX.…”

Immuno-enhancement effects of Shenqi Fuzheng Injection on cyclophosphamide-induced immunosuppression in Balb/c mice

“…Recently in China, Cy is being used in combination with various detoxifying and protective agents with the purpose of enhancing the efficacy and reducing the toxicity, such as many traditional Chinese medicinal herbs, Cassia occidentalis (Bin-Hafeez et al, 2001), Phyllanthus amarus (Kumar and Kuttan, 2005), Andrographis paniculata (Sheeja and Kuttan, 2006). Combining Chinese medicinal herbs with chemotherapy may improve quality of life, tumor response and performance status, as well as reduce the toxicity of chemotherapy.…”