Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.
Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.
Cancer Biology and Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, West Bengal, India.
Sujata
S
Das
Department of Zoology, University of Kalyani, Kalyani 741235, West Bengal, India.
Goutam Kumar
GK
Pradhan
Cancer Biology and Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, West Bengal, India.
Subhadip
S
Das
Department of Zoology, University of Kalyani, Kalyani 741235, West Bengal, India.
Debjani
D
Nath
Cancer Biology and Inflammatory Disorder, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, West Bengal, India. Electronic address: dassahakrishna@gmail.com.
Krishna
K
Das Saha
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001151:Arsenic / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002626:Chemistry, Pharmaceutical; D019610:Cytoprotection / Q000187:drug effects*; D004224:Diterpenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000975:Antioxidants; D004224:Diterpenes; D053769:Nanocapsules; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C030419:andrographolide; D001151:Arsenic
Andrographolide; Arsenic; Hepatoprotection; Nano andrographolide